INDEX
3
Presentation
4
The CNR Center: A short story
5
The Collaborative Relationship between the Department of Biology and the CNR Center
6
CNR and University personnel
7
Main Research Lines:
1) Metals and the Brain:
7
a. Aluminum as a Neurotoxic Agent: Relevance of the Metal Speciation in Human and
Experimental Toxicology.
10
b. Metallothioneins, Aging and Neurodegenerative Diseases
12
c. Aluminum and the Biophysical State of Cell Membrane.
14
2) Oxidative Stress induced by Photodynamic Effect on the Structure and Function of
cell and Subcellular Organelles
17
3) Sovramolecular Organization, Functional Regulation and bioinorganic Properties
of Invertebrate Oxygen Carriers
23
4)Photosensitizing and Phototherapeutic Properties of Porphyrins and their analogues
29
Publications
51
Communications
63
Reviews and Books Chapters
64
Books
65
International Projects
66
National Projects
66
International Collaborations
66
National Collaborations
67
International and National Conferences
67
Theses
70
PhD Theses
71
Acknowledgments
2
PRESENTATION
The Italian National Research Council (CNR) is currently in the throes of a major reorganization that will
shortly see its approximately 300 organizations (Institutes and Centers) rearranged into 100 National Institutes
through the merging or suppression of the original structures.
The CNR Center for Research in Biochemistry and the Physiology of Metalloproteins, situated at the Biology
Department of the University of Padua, has already been reorganized. In fact, by decree of the President of the
CNR on 18.4.2001, it has become a separate section of the Biomedical Technologies Institute (ITB) of Milan.
The ITB also comprises sections dealing with Epidemiology, Analytical Biochemistry, Bio-informatics and Cell
Pathology.
In its 30 years of activity, the Metalloproteins Center in Padua has naturally seen its research programs evolve
progressively from studies on hemocyanins alone to research projects on the Biochemistry and Biophysics of
Cuproproteins, Neurobiology, and Photobiology. These three decades have witnessed an important, close
scientific cooperation with the University of Padua, and the Biology Department in particular, based on a
convention for pooling ideas, people and equipment.
Moreover, in its 30 years of life, the Center has had numerous Italian and international visiting scholars as its
guests on scientific cooperation schemes, as well as students preparing their graduate and postgraduate
dissertations, or in postgraduate training, professional placements, etc., who have all contributed something of
their own resources.
It has been gratifying to see that the scientific productivity of the Metalloproteins Center has been one of the
most significant of all the research centers of the Italian National Research Council. Finally, over the years, the
Center has further developed its scientific heritage through important forms of cooperation with other national
and international research organizations, exchanging foreign visitors, organizing national and international
conferences, coping with an extensive publishing activity and more besides. We are therefore convinced that we
have made good use of the taxpayers' funds in the general interest of the community.
Though the future horizons emerging before us are still not entirely clear, I sincerely hope that - with the
reformed CNR – the cooperation between our section and the University of Padua will continue well into the
future, in our mutual interest and to the benefit of the scientific community.
Paolo Zatta
Section Manager
3
THE CNR CENTER: A SHORT STORY
At the end of August 1966, before definitively leaving the Naples Zoological Station where I had held the
position of Head of the Physiological Department since 1954, I organised a convention on “Biochemistry and
Physiology of Hemocyanins”, which represented the culmination of the research, funded by yearly contributions
from the NIH (National Institute of Health), which I had been conducting at that Institute for a number of years.
The convention was held at the Zoological Station from August 30 to September 1, 1966(1). It was attended by
about thirty Italian and foreign researchers who worked in the field of hemocyanins and metalloproteins. These
included E.F.G. van Bruggen, R. Lontre, A.C. Redfield, J.R. Redmond, E. Antonimi, A. Ehrenberg, C.B.
Malmstrom, G. Morpurgo, K.E. van Holde, R.J.P. Williams, B.L. Vallee and J. Wyman. That convention marked
the beginning of a series of workshops, held every two to three years at the principal European centres where
research on hemocyanins was being conducted. The last workshop was held in Roscoff, France, in the year 2000.
In 1967, we were informed that the NIH and the other American research centres intended to discontinue the
financial support accorded for all the research programs. In practice, this meant the sudden termination of all the
biological and biomedical research being done in Italy. All the interested parties decided to meet in Milan, where
we agreed to explain the situation and appeal to the Italian government for assistance. As a result, the National
Research Council (CNR) took over the various research programs and reorganised them as Research Centres
based at various Universities. This is how the CNR Centre for the Study of the Biochemistry and Physiology of
Hemocyanins and other Metalloproteins was established at the University of Padua at the end of 1969.
The research activities conducted by the Centre can be inferred from the list of scientific studies published to
date.
F.Ghiretti
Professor Emeritus of General Physiology
1. Physiology and Biochemistry of Hemocyanins. F. Ghiretti Editor. Academic Press, 1968.
4
THE COLLABORATIVE RELATIONSHIP BETWEEN THE
DEPARTMENT OF BIOLOGY AND THE CNR CENTER
When in 1971 I participated in the first competitive examination announced for a position as researcher at the
newly-established the Center for the Study the Physiology and Biochemistry of Hemocyanins, of the National
Research Council (CNR), I certainly never imagined that I would find myself in the position of Head of the
hosting Department, presenting the work the Center has carried out over 30 years of research.
Prof. Francesco Ghiretti, who the Science Faculty had asked to take the chair of General Physiology, arrived in
Padua with a research group that was studying proteins using biochemical methods. The event spurred the
interest and expectations of staff in the then Institute of Zoology, Comparative Anatomy and Genetics. Those
who were using completely different research methods, for years unsuccessfully tackling specific issues, nurtured
the hope that collaboration with the new group could help resolve their own problems. More in general, it was
thought that through collaboration, the new methodology's contribution could stimulate more up-to-date and
competitive research orientations.
Seminars and meetings were held to identify possible forms of interaction, but collaboration was difficult, as
research fields were very diverse and the issues confronted in the Center were quite particular, precisely because
they were linked to the specific goal of the institution itself, Hemocyanins.
As the years passed, the Center gained new personnel and collaborated to some extent with university
professors, whose backgrounds were nevertheless primarily in chemistry. Gradually, it began to grow
independent and almost separate from the hosting Institute, while it cultivated collaboration and comparison with
outside researchers who were interested in the same research issues. Things did not change much even when it
became necessary to broaden the field of research from Hemocyanins to other copper proteins, and later metal
proteins.
In the meantime, the Institute became the Department of Biology with the merging of the institutes of Botany
and Anthropology, the sphere of research diversified greatly, and the advent of new technologies in the field of
molecular biology and biotechnology gave it a different face even from its recent past in biological research.
Over the past few years, the CNR has also undergone a profound transformation that has substantially changed
the body's organization and use of resources, leading, among other things, to the closing of study centers as
autonomous structures and merging them into the Institutes of which they have become sections.
We are thus witnessing a significant innovative ferment that involves both the university and the CNR, creating
conditions in which the personnel of the new bodies can engage in profitable scientific collaboration, which has
actually developed in the recent past, but only sporadically. The solicitude with which the reseachers of the CNR
Section has initiated relationships with other members of the Institute of Biomedical Technologies into which
they have been merged and with university researchers who have been collaborating with this Institute for some
time, as well as the diligence demonstrated in soliciting research groups from the Department to interact with
their themes, are cause for hope that a CNR structure within the Department of Biology is not just a coincidence,
but rather an opportunity for organic, continuous and advantageous collaboration.
Arnaldo Cassini
Prof. of General Physiology
Head of Biology Department of the University of Padua
5
CNR and University personnel
Directors
Prof. Francesco Giretti
Prof. Anna Giretti Magaldi
Prof. Benedetto Salvato
Dr Paolo Zatta
1970-1990
1990-1996
1997-2001
2001-
CNR Personnel
Researchers
Dr Arnaldo Cassini
Dr Fernanda Ricchelli
Dr Laura Tallandini
Dr Paolo Zatta
1970-1974
19751970-1974
1976-
CNR Staff
Mr Ennio Carbone
Mr Antonio Cervellin
Mr Daniele Cervellin
Mr Sivano Gobbo
MrGiampaolo Rocco
Mr Giuseppe Tognon
F.A.
O.T.
CTER
O.T.
CTER
CTER
197719731971197819691974-
University personnel
Prof. Vincenzo Albergoni
Prof. Mariano Beltramini
Prof. Giulio Jori
Prof. Anna Ghiretti Magaldi
Prof. Benedetto Salvato
1970-1979
199119771970-1996
1970-
University Staff
Mr Renato Carbone
Mr Manuela Nicoletti
1970-1988
1982-1987
Members of the Scientific Committee
Prof. Lucia Banci
Department of Chemistry, University of Firenze
Prof. Umberto Belluco
Department of Industrial Chemistry,University of Padova
Prof. Maurizio Brunori
Department of Biochemistry, University of Roma
Prof. Luigi Casella
Department of Chemistry, University of Pavia
Prof. Heinz Decker
Institut für Molekular Biophysic, University of Mainz, Germany
Prof. Giorgio Giacometti
Department of Biology, University of Padova
Prof. Marino Nicolini
Department of Pharmacological Sciences, University of Padova
Prof. Ferdinando Palmieri
Department of Biology and Pharmacology, University of Bari
Prof. Giovanni Porcellati
Department of Biochemistry, University of Perugia
Prof. R.J.P. Williams
Department of Inorganic Chemistry, University of Oxford, UK
6
Main Research Lines
1 METALS AND THE BRAIN
a. ALUMINUM AS A NEUROTOXIC AGENT: RELEVANCE OF THE METAL
SPECIATION IN HUMAN AND EXPERIMENTAL TOXICOLOGY.
In spite of the natural abundance of Al(III) in the biosphere, no useful biological function of this metal ion has
been discovered so far. On the contrary, Al(III) is now well recognized as a neurotoxic metal center. The first
experimental toxicological study on Al(III) in experimental animals was reported by Döllken in 1897. The
scientific interest for the risk connected with the exposure of humans to aluminum uptake under most diverse
conditions has growth exponentially in recent years*. Metal uptake from dinking water, food and beverages,
pharmacological products, as well as as dust in working areas, antiacids, dialysis and enteral-parenteral fluids etc,
has been evaluated and monitored.
Apparently, living organisms are well and effectively protected from Al(III) aggression. It is generally accepted
that only1% out of the daily intaken Al(III) enters the blood stream and about 90% of this amount is excrete by
the renal function. Aluminum gains access to human body via two well established and one proposed pathways:
the G.I. tract and the lung tissue, and the olfactory way. Abnormal exposure to A(III) is experienced by uremic
patients and by occupationally exposed workers. The role of Al(III) as an etiopathological factor in the
production of dialysis dementia and dialysis osteomalacia is now well established. In both cases, neurotoxic
effect have been recognized, which can be effectively eliminated only upon prevention strategies. Critical
inspection of the literature reveals that an abnormally high uptale of aluminum is associated with development of
dialysis dementia, iron-adequate microcytic anemia, vitamin D-resistant bone disease and other. Al(III) has been
implicated during the last two decades as a potential neurotoxic factor in different brain conditions, like for
instance:
1. Dialysis encephalopathy
2. Alzheimer’s disease
3. Amiothrophic lateral sclerosis
4. Parkinsonism-dementia of Guam
5. Down syndrome with manifested Alzheimer’s disease features
6. Industrial exposure
7. Neurofibrillary degeneration adjacent to hemartoma
8. Striatonigral syndrome
9. Alcohol dementia with patchy demyelination
10. Senile plaques and neurofibrillary tangles in Azheimer’s disease
11. Aged human brain
The phenomenological connection between aluminum focal accumulation in pathological features of
Alzheimer’s disease (AD) like neurofibrillary tangles and senile plaques appears to be established by numerous
scientific reports, and the amount of positive observations, in this connection, represents a strong impulse to the
deepening of the knowledge on the molecular bases of aluminum neurotoxicity.
The relevance of a dismetabolism of aluminum to the etiology and pathogenesis of AD is still a matter of
intense debate and investigations. Biological, biochemical and bioinorganic models of aluminium toxicity are
certainly convenient tools for sheding light on this most intriguing topic. AD is an exceedingly complex disease
with manyfold histopathological and biochemical features and its is most likely a multietiological syndrome
As a matter of fact, a huge amount of experimental work has been carried out in this and other laboratories on
very many aspects of aluminium biology in the past two decades. However, it has become increasingly apparent
that even the simplest experimentation with aqueous Al(III) has to face with the intrinsic complexity of the
Al(III) speciation in neutral solutions and this subject has been recently reviewed by our research group in some
comprehensive reviews.
In pure phenomenological terms, the interaction between Al(III) with biological systems is documented by an
impressive number of papers (ca. 1000/year). In spite of this abundant literature, direct information on the
molecular bases of Al(III) biological activity are rather scanty. The reason for this unusual situation is at least due
two main reasons:1) in the very large majority of the experimental toxicology protocols Al(III) was administered
7
either under ill-defined pH conditions or as ill-defined mixture of various chemical species in the neutrality
range, and 2) very few research groups investigated on the specific biological acitivity of Al(III) administered
under precise chemical forms and on with biologically relevant macromolecules. As a matter of fact, researchers
are now challenged to interprete an enormous amount of biological, Al(III)-related, phenomena on the basis of a
dearth of bioinorganic molecular information.
A conceptual experimental breakthrough aimed to circumvent point 1) and 2) was independently proposed in
our and other laboratories in 1986. The basic intuition is the employing of Al(III) complexes bearing:
a. a defined molecular structure in solutions under the actual employment conditions
b. net zero electrical charge
c. high hydrolytic stability
d.defined hydrophilic/hydrophobic character measured in n-octanol/water partition coefficients
The combination of these requisites offers the possibility of using artificial toxicants for which it is possible to
calculate the metal speciation when biological system is exposed to the synthetic toxicant. Thus, under these
conditions, dose-response relationships become reliable and molecular models of Al(III) toxicity may be reliably
developed.
In the absence of a strong coordination agent, the aqueous solution chemistry of Al(III) is seemingly simples.
The thermodynamically predicted species which dominate at pH 7.5 are Al(OH)4- (10-6.86 M) and Al(OH)3 ( 108.10
M) at an expected total metal concentration equal to 10 -7 M. Diversely complexes such as Al(acac)3 (acac=
acetylacetonate) and Al(malt)3 (malt = maltolate) appear to meet the requisites necessary to by-pass the
drawbacks outlined in points 1. and 2.
The equation dealing with the metal speciation in water of artificial toxicants bearing bidentate monoionic
ligands, are the following:
Ki
Al(L-L)3 + 6H2O <=> [Al(H2O)6]3+ + 3 L-L(1)
3 L-L- + 3H2O
Kb
<=> 3H(L-L) + 3OH-
(2)
Kb
Al(H2O)63+ + 3OH- <=> Al(OH)3 + 6H2O
(3)
Kdec
Al(L-L)3 + 3H2O <=> Al(OH)3 + 3Al(L-L)
(4)
As a paradigmatic example in order to confirm our model we investigated the effect of Al(III) speciation of
blood-brain barrier (BBB) permeability by administering Al(acac) 3 (hydrolytically stable and lipophilic) and
Al(malt)3 (hydrolytically stable and hydrophilic) by i.p. injection in rats. As expected, while the action of Al(III)
on BBB was confirmed, new aspects of this biological effect became apparent. In fact, while Al(malt) 3 produced
a transient effect lasting few hours, Al(acac)3 caused an almost irreversible increase of BBB permeability.
Aluminum accumulation could be observed only in the neurons of the cerebral cortex from rats treated with the
more lipophilic compound. Diversely, Al(malt)3 revealed positivity for aluminum only on the microvessels.
Several other biological models were utilized to better understand the Al(III) speciation effect and its relevance
in various physiological as well as biochemical pathways. The following table briefly summarizes the main
findings on the effects produced by Al(III) in several biological targets as observed in our laboratory.
SOME EFFECTS PRODUCED BY ALUMINUM(III) ON VARIOUS BIOLOGICAL TARGETS
1.
2.
3.
4.
5.
6.
Inhibition of proteases (trypsin and -chymotrypsin)
Activation of Acetylcholinesterase
Activation of Hexokinase
Activation of Na+/K/ATPase
Inhibition of Ca2+/Mg2+ ATPase
Modification of the activity of some enzymes of the Krebs cycle
8
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17
Modification of the activity of some lysosomal enzymes
Alteration of the permeability of the blood-brain barrier
Alteration of the cell membrane fluidity
Alteration of intracellular calcium
Alteration of mitochondria metabolism
Alteration of lysosomal proton pump
Alteration of the functionality of VDAC channels
Neurotogenic effect on neuroblastoma cells
Neurotrophic effect on nervous system at low concentrations
Indirect stimulation cell membrane peroxidation
Alteration of the activity of SOD, Glutathione peroxidase and Catalase
Relevant books and Reviews from our laboratory
Aluminum in Chemistry, Biology and Medicine (1991) Nicolini M., Zatta P., Corain B. (Eds). Raven Press, pp.
117.
Aluminum in Chemistry, Biology and Medicine (1994) Nicolini M., Zatta P., Corain B. (Guest eds). Life Chem
Reports 11: 1-267.
Non-Neuronal Cells in Alzheimer’s Disease (1995) Zatta P. and Nicolini M.(Eds), World Sci., Singapore, pp.232.
Aluminum in Infants’ Health and Disease. (1997) Zatta P. and Alfrey A., World Sci. Publ., Singapore, pp. 245.
Alzheimer’s Disease and Related Disorders (1992) Nicolini M., Zatta P., Corain B. (Eds), Pergamon Press pp.
474.
Aluminum Chemistry (1996) (Corain B., Bombi G.G., Nicolini M., Zatta P. (Guest eds) (Special issue) Coord.
Chem. Rev. pp. 404.
Aluminum Chemistry (2002) (Zatta P., Guest ed.) (Special issue) Coord. Chem. Rev. (In press).
Further information can be seen on the Web site:
www.bio.unipd.it/~zatta/aluminum.html
* The number of scientific publications reported in Medline on aluminium per years is about 1200.
** Aluminium and Alzheimer’s disease. The science that describes the link. (2001) ((Exley, editor) Elsevier,
Amsterdam, Holland.
9
b. METALLOTHIONEINS, AGING AND NEURODEGENERATIVE DISEASES
In the human brain, aging is considered as one of the most relevant risk factors for neurodegenerative disorders
and a state in which pathological alterations may exist without an apparent clinical expression. In addition, in
aging brain, genetically programmed time-associated modifications in cells may increase their susceptibility to
dangerous environmental factors like for instance, hormonal changes, infective diseases, immunological disorders
etc., and consequently lead to a variety of pathological events observed in the aged brain.
Free radicals are highly reactive chemical species with an unpaired electron in an atomic or molecular orbital.
In biological systems in the presence of transition metals like iron, copper, manganese and others, the most
relevant form of radicals are superoxide and hydrogen peroxide, that are dangerous in that they attack proteins,
nucleic acids and membranes containing polyunsaturated fatty acids. Particularly in the brain free radicals can be
produced by catecholamine mismetabolism especially when a deficiency of antioxidants occurs. In Alzheimer’s
disease (AD) brain lesions are present that are typically associated with attacks by free radicals (e.g., DNA
damage, protein oxidation, lipid peroxidation, advanced glycosylation end products, etc.) in the presence of
metals that catalyze the production of such radicals. Neuroinflammatory phenomena are also important factors in
neurodegenerative diseases in that they increase formation of reactive oxygen species (ROS) and nitrogen species
that could be a major risk in the neurodegenerative development. Glial cells and astrocytes in particular, play a
central role in the inflammatory phenomena, and astrocyte activation is a relevant marker for neurodegenerative
disease like Alzheimer’s, Binswanger’s disease, Down’s syndrome etc. The brain in fact is considered very
sensitive to oxidative damage in that is enriched in the more easely peroxidizable fatty acids and with about 20 %
of the total O2 consumption with its 2% with respect to all whole body mass. In recent years considerable data
support the hypothesis that the brain from AD subjects is under increased oxidative stress and this is considered
as a relevant issue in the pathogenesis of neuronal degeneration. Amyloid -peptide, the major constituent of the
senile plaques (SP) in AD brain, has been shown to be a source of free radicals.
In the brain, metallotioneins (MT-I-II) were identified in pia mater, ependymal cells, astrocytes, glial processes
and microcapillaries. In the cerebellum MT-I-II were identified in the Bergmann cells, and in the protoplasmatic
astrocytes of the white matter. Among numerous hypotheses advanced to explain some neurodegenerative
diseases the relevance of free radicals has been recently and strongly raised by some authors. In this connection
the role played by astrocytes appear to be of paramount importance in that they generate the highest
concentration of -amyloid of all cell type so far tested. In addition, reactive astrocytes increase the production of
the amyloid precursor protein (APP) which in turn may recruit other reactive astrocytes and microglial cells to
increase the APP production. It has been recently reported that in AD subjects cerebral white matter contains
numerous MT-I-II-expressing astrocytes with an intense immunoreactivity of the cell body. MT participate in
intracellular defense against ROS and nitrogen species. Chronic inflammation in AD has been postulated to
raising the possibility that the etiology of AD have an immunological component. Cytokines and IL-1, for
instance, elevated in AD, induce MT-I-II production in astrocytes suggesting that these proteins may have a
relevant role in providing long-term protection against oxidative damage, injury and inflammation with a
multiple compensatory mechanism involving the osmotic regulation of some metal ions. Thus, while it seems
rather clear the overexpression of MT-I-II in the astrocytes from AD as well as from other neurological disorders,
more controversial appears the presence, the role and the meaning of MT-III in connection with some
neurological disorders. In AD, for instance, some authors observed that MT-III is down-regulated, while other
claimed that the reduction in the expression of MT-III is most likely due to several other factors not necessarely
linked to AD pathology. MT-III is growth inhibitory factor (GIF) particularly abundant in glutamatergic neurons
that releases Zn from synaptic terminals, and in Zn-containing neurons of the hippocampus where it could play a
role in neuromodulation in a way yet to be so far well understood. MT-III, besides in neurons, is also induced in
astrocytes in the cerebral cortex in cases of meningitis, Creutzfeldt Jacob disease as well as in reactive astrocytes
sorrounding cerebral infarct. It has been claimed also that GIF is reduced in a subset of reactive astrocyrtes in
lesioned areas of degenerative diseases such as AD, multiple-system atrophy, Parkinson’s disease, progressive
supranuclear palsy and amyothrophic lateral sclerosis in relation to neuronal loss. Noteworthy, MT-III deficient
mice show decreased concentration of Zn in several brain regions and they are more susceptible to seizures
induced sperimentally with consequent greater neurons injury. Conversely, transgenic mice with high level of
MT-III are more resistant to hippocampal neurons injury induced by seizures. According to Masters et al. (1994),
MT-III may participate in the utilization of Zn as a neuromodulator. In the central nervous system, Zn is present
in all regions in a rather high concentration with a definit, however, not well defined role in neurochemistry. Zn
interacts with enzymes and proteins including transcription factors which are critical for cell survival and could
be linked to apoptotic processes. The concentration of Zn, Cu and other metal ions has been reported to be altered
in several neurological disorders like Alzheimer’s, Parkinson’s, Huntington, Pick disease, alcoholism,
schizophrenia, Down’s and Wernike-Korsakoff syndrome, amyotrophic lateral sclerosis and others. In addition,
concentration of Cu, Fe and Zn were measured in the rims and cores of SP and in the neuropil of the amygdala of
AD patients. Both an excess or a deficiency of Zn have been reported to be associated with neurological diseases.
Zn loss is associated with anorexia, hyposmia, cerebral dysfunction and it has potent inhibitory action on
10
glutamate decarboxylase. It serves in a double role in initiating amyloid deposition in AD and then being
involved in mechanisms attempting to quench oxidative stress and neurotoxicity derived from amyloid mass. Zn
has a role as a neurosecretory product highly concentrated in synaptic vesicles of a specific contingent of neurons
that represent a subset of glutamatergic neurons. Related to AD, the APP is proteolitically processed by an secretase to release a soluble form of an APP derivative and interestingly to note -secretase is a Znmetalloprotease. In addition, soluble human amyloid binds specifically Zn and rapidly becomes a strongly
insoluble compounds which easely aggregates. In this connection, although, a single essential function of MT has
not been found yet, MT evolved as a mechanism able to regulate Zn levels and its distribution inside the cell. The
ubiquitously essential distribution of Zn coincides with the ubiquitous distribution of MT-I-II. These proteins are
produced by reversible activation of Zn interaction with Zn-finger domain of the metal-responsive transcription
factor (MTF) which activates MT-gene in response to metals and oxidative stress. MTF is thus a sort of sensor of
free Zn pool in the cell which can change in response to chemical diverse inducers. Regulation of MT genes by
metals and oxidative stress involves multiple signaling pathways which depend on the species of metal ion and
the nature of the oxidative stress. Thus, Zn metabolism could be relevant in the brain in the neuropathogenesis of
AD and other neurological disorders through the physiopathological expression of MT.
In conclusion, the role of MT, generally speaking, is yet to be fully understoood, however, it appears that while
MT-I-II are induced in relation to the progression of the age-related modifications in the brain and they play an
important role in the protection of tissue from toxic insults (e.g., free radicals, metal ion mismetabolism)
responsible for the brain aging; diversely, MT-III could play a role in maintainance of Zn-related essential brain
functions.
References
Hidalgo J., Aschner M., Zatta P., Vasak M. (2001) Roles of the metallothionein family of proteins in the central
nervous system. Brain Res. Bull. 55: 133-146.
Mocchegia E., Giacconi R., Cipriano C., Muzzioli M., Fattoretti P., Bretoni-Freddari C., Isani G., Zambenedetti
P., Zatta P. (2001) Zinc-bound metallothioneins as potential biological markers of ageing. Brain. Res. Bull. 55:
147-155.
11
c. ALUMINUM AND THE BIOPHYSICAL STATE OF CELL MEMBRANE
In the last ten years a lot of progress has been made in a better understanding the properties of aluminum with
respect to its impact in the biosphere. However, in spite of an enormous number of scientific papers on the
chemistry, bioinorganic, biochemistry as well as toxicology of aluminum, it is still premature to define the
precise molecular mechanism/s that could fully explain the influence of this metal ion on the biological targets,
including cell membranes. Experimental data confirm that aluminum is able to deeply alter the molecular
structure of the lipid bilayer, modifying thus, biophysical and physiological properties of the cell membrane such
as fluidity, rigidity, transduction of signals, channel permeability and protein activity. Furthermore, to
complicate more the scenario, a great deal of differences has been found between data obtained from in vitro and
in vivo experimentation. Often, results obtained by in vivo models are more dramatically relevant than those
obtained using in vitro models, suggesting a more holistic action of aluminum toward biological targets.
A better understanding of the role of the metal speciation appears to be one of the most important issues to be
studied in order to understand aluminum toxicological properties. This aspect is extremely important if it is
considered that aluminum is present everywhere in our everyday life, like in food, beverage and pharmaceutical
products.
In relation to a possible connection between aluminum and Alzheimer’s disease, while a directed connection
with the etiopathogenesis of this disease is still to be proven, several elements seem to indicate that the metal ion
could be somehow involved concurring in the aggravation of some pathological events observed in this
devasting pathology, especially in those individuals more prone to aluminum uptake, on the bases of the
following observations:
-Aluminum produces a profound alteration on the biophysical status of biomembranes, consequently, it can
induce a strong modification of cell membrane anysotropy alterating strategic physiological functions on the
lipid metabolism as well as on the biochemical and physiological properties of proteins associated to the lipid
bilayer.
-The higher presence of phosphatidylcholine derivatives in the cell membranes of AD (Pettegrew et al., 1984;
Wurtman et al., 1990), could facilitate an Al3+ overaccumulation in the surface of membranes. In addition, the
hyperphosphorylated tau proteins associated to the cytoskeleton, as observed by several authors in AD, is an
elective place for Al3+ accumulation as hypothesized by Zatta (1995) and partially proven (Shin et al., 1995; Shin
et al., 1997) with a consequent possible blockage of the axonal flux (Zatta, 1995).
-The interaction between Al and biomembrane produces a significant rigidification that could contribute to a
reduction of the width of the lipid bilayer as it has been observed in AD by Mason et al.,(1993), favoring thus the
abnormal exposure of the amyloid segment of the APP to a more strategic proteolysis by some putative yet to be
discovered secretase.
-Al altering membrane biophysical properties of mitochondria and ER, and inhibiting Ca 2+-ATPase activity,
(Mirzabekov et al., 1993; Gandolfi et al., 1998) can potentially alter Ca 2+ homeostasis influencing apoptotic
phenomena.
-The observed structural destabilization of the cell membrane by Al could induce a more relevant production of
free radicals by the transition metals, mainly Fe(II) increasing oxidative phenomena (Zatta et al., 1989; Zatta et
al.,1997; van Rensburg et al., 1992) as observed in AD.
-Al acting as a membrane destabilizer at the BBB level can deeply modify its permeability as it has been
observed in experimental animals in a speciation-dependent way (Favarato et al., 1992).
Further studies are thus necessary to better understand the role of Al in connection with AD, if any. It is a fact
that the molecular, biophysical and chemical bases of individual sensitivity to aluminum, and the consequent
involvement as a potential risk factor or at least as an aggrvating cofactor for AD, as well as for other
neurodegenerative diseases, is still an issue to be explored in the near future.
REFERENCES
Favarato, M., Zatta, P., Perazzolo, M., Fontana, L., Nicolini M., (1992) Aluminum (III) influences the
permeability of the blood-brain barrier to [14C]sucrose in rats. Brain Research 569, 330-335.
Gandolfi, L., Stella, M.P., Zambenedetti, P., Zatta, P. (1998) Aluminum alters intracellular calcium homeostasis
in vitro. Biochimica & Biophysica Acta. 1406, 315-320.
Mason, R.P, Shoemaker, W.J, Shajenko, L., Herbette, L.G (1993) X-ray diffraction analysis of brain lipid
membrane structure in Alzheimer’s disease and beta-amyloid peptide interactions. Annals of the New York
Academy of Sciences 24, 54-58.
12
Mason, R.P., Trumbore, M.W., Pettegrew, J.W. (1996) Molecular membrane interactions of a phospholipid
metabolite. Implications for Alzheimer’s disease pathophysiology. Annals of the New York Academy of Sciences
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Mirzabekov, T., Ballarin, C., Nicolini, M., Zatta, P., Sorgato, M.C. (1993) Reconstitution of the native
mitochondrial outer membrane in planar bilayer. Comparison with the outer membrane in a patch pipette and
effect of aluminum compounds. Journal of Membrane Biology 133, 129-143.
Pettegrew, J.W., Kopp, S.J., Dadok, J., Minshew, N.J., Feliksik, J.M., Glonek, T., Cohen, M.M. (1984) Chemical
characterization of a prominent phosphorylmonoester resonance in animal. Huntington’s and Alzheimer’s brain:
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P and 1H NMR analysis at 4.7 and 14.1 tesla. Annals of Neurology 16, 136-138.
Shin, R.W., Lee, V.M., Trojanowski, J.Q. (1995) Neurofibrillary pathology and aluminum in Alzheimer’s
disease. Histology and Histopathology 10, 969-978.
Shin, R.W., Lee, V.M., Trojanowski, J.Q. (1997) Aluminum modifies the properties of Alzheimer’s disease PHF
tau proteins in vivo and in vitro. Journal of Neurosciences 14, 7221-7233.
Van-Rensburg, S.J., Carstens, M.E., Potocnik, F.C., Aucamp, A.K., Taljaard, J.J., Koch, K.R. (1992) Membrane
fluidity of platelets and erythrocytes in patients with Alzheimer’s disease and the effect of small amounts of
aluminum on platelets and erythrocyte membranes. Neurochemical Research 17, 825-829.
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Choline levels the regulation of acetylcholine and phosphatidylcholine synthesis, and Alzheimer’s disease. In
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Beckmann) Springer-Verlag, Wien, New York, 211-224.
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Zatta, P. & Nicolini, M. (Eds) (1995) Non-Neuronal cells in Alzheimer’s disease. World Science. Singapore,
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Zatta, P., Zambenedetti, P., Toffoletti, A., Corvaja, C., Corain, B. (1997) Aluminum(III) induces alterations on
the physical state of the erythrocytic membrane: an ESR evaluation. Journal of Inorganic Biochemistry 65, 109114.
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London.
13
2. OXIDATIVE STRESS INDUCED BY PHOTODYNAMIC
EFFECTS ON THE STRUCTURE AND FUNCTION OF CELLS
AND SUBCELLULAR ORGANELLES
This research project was aimed at the understanding of the mechanisms of photosensitization, i.e. the process
induced by highly toxic, reactive oxygen species (ROS), produced after irradiation by UV-visible light of some
fluorescent molecules (in particular, porphyrins and analogous compounds, such as phthalocyanines,
naphthalocyanines etc.) that is involved in some types of cell damage and death.
Porphyrins have been widely studied as sensitizers of living organisms in the light-promoted reactions. The
porphyrin-mediated photodamage is mainly due to the production of singlet oxygen ( 1O2), through an electronic
energy transfer from the first excited triplet state of the sensitizer to the molecular oxygen in its ground state
(triplet). The photosensitization process can be highly noxious and cause irreversible cell damages, as observed in
human porphyria or in skin lesions such as erythema and cancer. However, porphyrins and other photosensitizers
have found useful biomedical applications in the treatment of several deseases, as, for ex., in the photodynamic
therapy of tumors (PDT) and in the destruction of atheromatous plaques and psoriatic lesions. Pioneering studies
concern the use of photosensisting molecules as antibacterial and antiviral agents.
Most porphyrins which have been tested both in vitro and in vivo carry on their photoactivity after preferential
association to membranes (in particular, plasma, mitochondria and endoplasmic reticulum membranes), and the
targets of photodamages are proteins and lipids. The extent of photodamage mainly depends on the sensitizer
aggregation state (only monomeric species are photoactive) and its distribution pattern into cells and subcellular
organelles. The maximum photoprocess efficiency, in fact, is reached when photosensitizer and target are
localized in close proximity, being the diffusion
in biological material) owing to their high reactivity.
This research was focused on the characterization of the photochemical and photophysical properties of
photosensitizing agents in model and biological membranes as well as on the study of their uptake and
photodamage mechanisms on functional activities of cells and subcellular organelles. Particularly studied was the
correlation between the distribution properties of porphyrins and derivatives and their photosensitizing efficiency
in mitochondria, which are primary targets of the photodynamic effect in vivo. The distribution pattern of these
molecules in membranes is influenced by several factors including the degree of dye hydrophobicity, the nature
of the carrier and the incubation time with the membrane. As an example, hematoporphyrin (HP), a
photosensitizer characterized by a moderate degree of hydrophobicity, preferentially partitions to protein sites of
the inner mitochondrial membrane (IMM), which exhibits a higher protein content (21% of total protein) as
compared to the outer membrane (OMM , 5% of protein). It has been postulated that the HP-binding sites are
localized on the ADP/ATP translocase: actually, at mild irradiation conditions, the most sensible function to the
HP photodynamic action is the ADP transport whereas other enzymes involved in the ATP synthesis, such as the
ATP synthase or the Pi carrier as well as the enzymes of the respiratory chain and the Ca 2+ transport are less
affected. The enzymes of the outer membrane, matrix and intermembrane space require massive light doses for
the photodegradation. HP distribution pattern in mitochondria is not affected by the nature of the transport system
to the membrane. More hydrophobic dyes than HP, such as protoporphyrin (PP), localize in mitochondrial lipid
domains and their distribution properties are largely modulated by the chemical composition of the carrier and the
incubation time. At short incubation periods (<2 min ), liposome-bound PP accomodates in lipid domains of the
IMM provided that the liposomal carrier is enriched in cardiolipin; in lipid domains of the OMM if the dye is
transported by cholesterol-rich liposomes. Thus, PP-uptake by mitochondria is controlled by the affinity in lipid
composition between the carrier and the acceptor membrane. The dependence of the uptake properties on the
lipid composition of the carrier is lost after incubation periods longer than 2 min, due to a migration of PP to
IMM. In the latter case, the extent of ADP transport inhibition by irradiated PP approaches that shown by HP.
Highly hydrophobic dyes, such as Zn2+ -phthalocyanine (ZnPc), interact predominantly with lipid domains of the
OMM indipendently of the transport system and incubation time.
The transport system of photosensitizers in vivo is a crucial determinant. A pimary goal in the photodynamic
treatment of tumours, for ex., concerns the achievement of tumor selective targetting by the photosensitizer. To
this aim, most researches are oriented to obtain the specific release of the drug to the low density lipoproteins
(LDL). It has been credibly hypothesized that, in vivo, LDL play the role of preferential carriers of the sensitizer
to tumoral tissues. In fact, LDL interact with several types of tissues, in particular hyperproliferating tissues, via
an endocytosis-mediated process. In agreement, LDL-associated photosensitizers administered to tumor-bearing
rats accumulate preferentially in malignant tissues as compared to the drugs freely dissolved in aqueous solutions
or incorporated in other lipoproteins lacking of specific receptors on plasma membranes. The selective sensitizerserum lipoproteins interaction is obtained after incorporation of the drug in liposomes. In fact, while aqueous HP
or HP dimethyl esther or ZnPc for ex., distribute into at least three classes of serum proteins (albumins, globulins,
14
lipoproteins), a selective association to lipoproteins is obtained after incorporation of the drug in liposomes of
dipalmitoyl phosphatidylcholine (DPPC). The efficiency of the drug release process depends on the chemical
composition of the carrier. Liposomes carrying phospholipids characterized by shorter hydocarbon chains, such
as dimiristoyl phosphatidylcholine (DMPC) , lead to an aspecific distribution of the sensitizer in different serum
proteins.
Recently, this research has been focused on the effects of the photosensitization-mediated oxidative stress on
the permeability transition (PT) process of the mitochondrial inner membrane, that has been postulated to be
involved as early step in the cascade of events leading to apoptosis or programmed cell death. The transition from
the impermeable to the permeabilized state of the inner membrane after Ca 2+ accumulation by mitochondrial
matrix is characterized by the opening of a cyclosporin A-sensitive proteinaceous pore that leads to mitochondrial
uncoupling, matrix swelling, permeation to solutes with molecular masses up to 1500 D, Ca 2+ efflux and loss of
matrix components. This program can be subdivided into the following three lines :
a. Relationship between the photosensitizer microenvironment and its photosensitizing
properties..
One of the major parameters that influence the sensitizer photoactivity in biological membranes is the nature of
its microenvironment after incorporation in the membrane. Inserting the sensitizer deeper within the hydrophobic
membrane bilayer increases the dwell time of singlet oxygen in the membrane ( 1O2
in
apolar media have been reported) whereas a partition to the lipid/water interface or to the aqueous phase leads to
a very rapid decay of 1O2 which is quickly deactivated by solvent molecules (1O2 lifetime in H2O is about 3 s).
Therefore, in cellular systems the 1O2 -induced photodamage is higher when both sensitizers and targets are
localized in the membrane hydrophobic regions rather than in the cytoplasm or in the external medium. The
maximum effect will be obtained when sensitizer and target are situated in close proximity. The molecular nature
of the photosensitizer microenvironment determines the type of the final target of the photosensitization process
thus leading to different cell responses to the photodamage. On these basis, it is very important to search for those
conditions that could permit to address the sensitizer to a particular microenvironment thus discriminating the
photodamages on different cell functional activities. As an example of this approach, it has been shown that
irradiation of mitochondria in the presence of HP produces 1O2-mediated oxidative effects that lead to inhibition
of the mitochondrial PT. This effect is quite unexpected since it seems a general rule that oxidative stress,
independently of the reaction mechanism of the different oxidative species, cause induction of the PT. The effect
has been attributed to degradation of critical histidines, present in one of the regulatory sites of the PT process. In
contrast with what observed for HP, trimethylpsoralen (TMP), a structurally different molecule whose
photoactivating effect is also mediated almost exclusively by 1O2 , induces opening of the PT pore after
irradiation as a consequence of critical thiols oxidation and formation of cystine, a reaction that increases the
probability of the PT process. Although both HP and TMP are bound to proteins of the inner membrane. it has
been ascertained that their interaction sites are different. This research has demonstrated that the same reactive
species can activate or inhibit a cell function (as the mitochondrial PT) depending on the site where it is produced
in a biological membrane.
b) Generation of reactive oxygen species by photoactivated cell-probes and implications for
studies of cellular functions.
Because of the key role performed by mitochondria in cell metabolism as well as in the regulation of normal
cell functions of particular interest is mitochondrial photosensitization. On these bases, photosensitisers
specifically targeted to mitochondria may provide versatile applications in studies of mitochondrial contribution
to processes leading to cell death. On the other hand, photochemical effects are undesirable when fluorescent
probes are used for studies of cell viability and microscopic imaging. Microscopic observations using
epifluorescence or laser illumination in confocal microscopy may result in the perturbation of cellular structures
and induction of severe cell damage if dye concentrations and exposure times to the light are not properly tested.
Some of these probes have been demonstrated to be highly photoreactive and lead to cell apoptosis after exposure
to light sources used in microscopy studies. By our studies, calcein, a water-soluble, polyanionic fluorescein
derivative which is currently used for probing membrane integrity and permeability and in studies of
mitochondrial permeability transition in cells by microscopy fluorescence imaging, was recently found to induce
photosensitized alterations in isolated mitochondria thus suggesting potential artifacts in confocal microscopy
studies of cells. These results suggest that a thorough investigation should be performed on the possible
photosensitizing effects elicited by other fluorescent probes. In particular, various potentially phototoxic cationic
dyes, such as rhodamines, are used to measure the mitochondrial membrane potential (m) at the single cell
level, in conjunction with microscopy techniques . The prolonged exposure time required to obtain good
15
resolution can dramatically affect both cell viability and mitochondrial function. This problem is worsened in the
case of confocal microscopy, where cells are exposed to the high intensity of laser beams. Because of their
phototoxic effects, potentiometric fluorescent probes are in fact under investigation as potential therapeutic
agents against various types of tumors , which appear to accumulate these molecules more efficiently than
normal, non transformed cells. Thus, the fluorescent probes could contribute to cause or potentiate rather than
simply measure the changes of m. On these basis, work is in progress to define the experimental conditions
which allow a safe use of these probes in intact cells.
c) HP-fluorescence anisotropy studies in relation to the mitochondrial permeability transition.
Induction of the mitochondrial permeability transition (PT) gives also rise to modifications in the membrane
dynamic properties. In the lipid regions of the bilayer such changes arise only from the modulating effects of the
PT-induced osmotic swelling and/or membrane potential decay, as sensed by the fluorescence anisotropy changes
of 1,6-diphenyl-1,3,5-hexatriene (DPH) for highly hydrophobic domains and 1-anilino-8-naphthalene sulfonate,
(ANS) or 1-[4-(trimethylamino)phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH) for the phospholipid headgroup
areas. Studies of the PT-induced anisotropy changes of hematoporphyrin (HP) as reporter of membrane protein
regions indicate that the above-mentioned effectors cannot account alone for the total PT-effect and the protein
alterations can be mostly attributed to conformational variations of the HP-binding sites during the assembly of
the PT pore. The specificity of HP in sensing changes in membrane structure during pore opening was ascribed to
a strategic location of the dye in protein sites of the inner mitochondrial membrane which appear to participate in
pore formation or regulation. This interpretation is strenghtened by comparative studies of mitochondrial
interaction with HP and a structurally different fluorescent probe, namely 3,4´,5-trymethylpsoralen (TMP). Both
dyes bind to inner membrane protein sites; however, the TMP-anisotropy variations during opening of the PT
pore reflect only structural changes induced by the potential decay. The strict relationship between the dynamic
properties of HP-binding area and the conformation of the pore complex is further supported by the fact that
similar changes of HP-anisotropy are observed after triggering the pore on different key sites which are activated
by various inducers (FCCP, PhAsO, DIA etc.).
On these bases, HP fluorescence anisotropy can be considered a promising tool to monitor the PT pore
characteristics, because it directly follows the conformational properties of the pore constituents rather than the
effects of the pore produced on the whole mitochondrial structure (swelling, potential decay, loss of calcium,
release of matrix components).
16
3. SOVRAMOLECULAR ORGANIZATION, FUNCTIONAL
REGULATION AND BIOINORGANIC PROPERTIES OF
INVERTEBRATE OXYGEN CARRIERS
Why invertebrate oxygen carriers?
Invertebrate oxygen carriers are unique macromolecules. Their peculiarity mainly resides in the oligomeric
structures that exhibit high levels of complexity. Proteins from organisms that belong to different phyla have
quaternary structures that can be related to distinct topological models. Within the same phylum, however, the
different structures are related to the same topological model. Different kinds of subunits constitute the different
functional aggregates. This large structural differentiation manifests itself in a significant functional flexibility
whose description requires allosteric models of increasing complexity. The ultimate aim of this research program
is to study the correlation between the structural modification at the active site induced by oxygen binding and
the changes in shape of subunits and of the whole molecules; on these changes is based the cooperativity of these
proteins. To reach this aim we have integrated different experimental approaches that allow for the investigation
on different dimensional scales.
In invertebrates four classes of oxygen carriers can be singled out on the basis of their prosthetic groups:
Hemoglobins (Hb, heme-proteins), Chlocruorins (Chl, chlorocruoro-heme proteins), Hemerithrins (Hr, non-heme
iron) and Hemocyanins (Hcs, dinuclear copper). The molecular complexity is different within the four classes,
yet a precise description of the functional regulation mechanism is still missing even in the case of the simplest
cases.
We want to establish the relationships between their functional properties and the structural modifications in the
active site region induced by oxygen binding to the various aggregation states that are characterised by different
affinities for this ligand. Furthermore, we also address the role of the polypeptide chains heterogeneity on the
allosteric properties.
Our approach to study such structure-functions relationships involved different levels of complexity. One level
of complexity concerns the presence in such proteins of metal ion(s) that are of fundamental importance for
coordinating molecular oxygen. As outlined above, the evolutionary strategies have selected copper and iron in
different complexes (iron-protoporphiryn or dinuclear sites). In Hbs, the reactivity of the metal prosthetic group
is strongly dominated by the presence of the porphyrin ring that involves four out of six coordination positions of
the metal ions. A great deal of work is available in literature on the dependence of the affinity for dioxygen as a
function of: - distortions of the tetrapyrrol ring, - bonding distance between iron and proximal histidine, position of the iron with respect to the plane defined by the tetrapyrrol nitrogens, - position of the distal
histidine with respect to the iron. Hc and Hr have dinuclear metal active sites where the two metal ions, directly
bound by the protein matrix, are not equivalent in their reactivity and accessibility to exogenous molecules such
as dioxygen, although in both cases the reaction between the O 2 molecule and the bimetallic centre is a reversible
redox process.
The second level of complexity involves the whole molecule where the oligomeric composition and the
hierarchical interactions among different subunits play fundamental roles for the onset of cooperative phenomena
and for the functional modulation as a response of external stimuli.
Hcs have an active binuclear site with copper of type 3, directly bound to six histidine nitrogens of the protein
chain and located within hydrophobic pockets, shielded from the external media. Crystal structures are available
for a 50 kDa functional unit Odg from Octopus dophleinii for subunits a and b of Panulirus interruptus and for
subunit II of Limulus polyphemus. In arthropod Hcs the two copper(II) ions, labelled CuA and CuB, are bound
by three histidine residues each that are provided by a total of four different α-helical segments with antiparallel
orientation with respect to each other. An additional difference is observed in mollusc Hc where the Cu A is
coordinated to one histidine of a α-helix and to two histidines of a loop region, one of which is involved in an
unusual thioether bridge. The molluscan CuB, similarly to the CuA and CuB in the arthropod Hcs, is coordinated
by the histidines of a two α-helices motive. CuA and CuB are not equivalent and play different roles during the
biological function. The CuA copper(II) centre, that is more accessible in the binuclear site, controls the
reactivity of the site, while the second copper(II) centre (CuB) plays a complex role in controlling the local
conformation and providing electrostatic effects during the oxygenation cycle. Deoxy-Hc contains a di-Cu(I)
active site, whereas oxy-Hc is described as a -2:2 di-Cu(II)-peroxo complex. This peculiar bridging
coordination mode is responsible for the onset of an intense absorption band around 340 nm (~20,000 M-1cm-1
) attributed to peroxide-to-Cu(II) LMCT transitions. The unequivalence of the two metal ions is very evident in
the case of the di-iron site of Hr. In this case, the protein provides three and two histidine nitrogens for binding
Fe1 and Fe2 respectively. The two metal ions are bridged by two carboxylates and by a further ligand that, in the
17
deoxy-form, is an hydroxo-bridge for the two Fe(II). Dioxygen is bound as hydroperoxide to Fe2 and stabilized
by hydrogen bonding to an oxo-bridge between the two Fe(III) ions.
Such crystallographic evidences are in line with the solution studies on the non-equivalent reactivity of the
copper ions in Hcs that represented one of the main research interests at the CNR Centre.
Bioinorganic properties of the dinuclear copper site in hemocyanins
We have studied the rather complex chemistry of the Hc active site with respect to a number of reactions that
proved to be useful to probe the non-symmetric reactivity of the binuclear active site. Such reactions involve
coordination of exogenous ligands that are reversible as in the case of non ionic ligands like CO, thiourea,
thiocyanate, or promote specific reactions such as: copper removal, copper oxidation, electron transfer. In this
frame it has been demonstrated that the two copper ions are not kinetically equivalent with respect to reactions
that either change the oxidation state of the metal or remove the metal from the active site. Although the
dinuclear complex itself possess several elements of symmetry the cavity provided by the protein matrix imposes
a preferential path for the access of exogenous molecules. This non-symmetric exposure of the dinuclear metal
complex strongly affects the overall reactivity of the active site which is dominated by the metal ion occupying
the more exposed binding site (fast reacting site, FR-site), being the copper ion in the other site (slow reacting
site, SR-site) substantially shielded. Therefore, several studies describe a variety of reactions that yield
derivatives where the copper ion in the FR-site reacts specifically and only under more drastic conditions the
reactions involve both metal ions. The non-symmetric exposure of the dinuclear copper complex to the solvent
plays a role in the kinetics of copper removal by CN-, where the reaction has been described by a sequential
mechanism with marked differences in the reactivity of the two copper ions, to give first, a partially metal
depleted derivative, the ( --- , CuSR) semi-apo form and then the apo-form. The fluorescence properties of Hc are
an important spectroscopic probe that can be used to discriminate between the binding of the copper ion to the
SR-site and the FR-site. A significant quenching effect on the intrinsic fluorescence of Hc is observed only upon
copper binding to the FR-site, while no influence can be attributed to the metal ion in the SR-site. This
observation can be rationalised by the presence of one tryptophan residue close to only one of the copper in the
crystal structure of Panulirus interruptus Hc. On the basis of spectroscopic evidences it is now possible to infer a
correspondence between the crystallographic and the kinetic definition of the copper binding positions within the
active site interpreting the fast reacting site as Cu A and the slow reacting site as CuB. It is worth noting that the
non-equivalent exposure of the two metal ions in the active site derives from a structural characteristic of the
protein matrix itself and, hence, the difference in the reactivity is maintained also when the binding sites are
metal-depleted as in the apo-form. Consequentially, also the binding of metal ions to the apo-form may follow a
kinetic mechanism that implies consecutive reactions, in which the first metal ion binds at the FR-site and then
moves to the SR-site, living the FR-site again ready to bind the second metal ion. Thus, several procedures have
been developed in order to obtain metal binding to the apo-Hc form. Cu(I) ions can reconstitute native Hc under a
variety of experimental conditions. Also Co(II) ions, that have ionic radius similar to that of Cu(II), can be
coordinated by apo-Hc yielding either mononuclear or binuclear metal substituted derivatives where Co(II) is
specifically bound either to the FR-site or to both sites. Furthermore, the Cu(I) ion of the FR-site of deoxy-Hc can
be directly exchanged with Co(II) yielding the specific mixed metal [Co(II)FR-Cu(I)SR] derivative. A mononuclear
FR-site derivative has been prepared using Cd(II) ions which have a ionic radius quite similar with that of Cu(I).
As observed for copper-containing Hc forms, the fluorescence emission of the metal substituted derivatives is
affected by metal binding in the FR-site.
The non-symmetric exposure of copper ions to exogenous molecules is evident also when the reactivity of
copper ions is probed with respect to oxidation reactions under controlled conditions. A semi-met-Hc derivative
can be prepared by selective oxidation one Cu(I) ion of the dinuclear cuprous site of deoxy-Hc with NO2 whit
production of nitric oxide. A noteworthy aspect of this reaction scheme is its analogy to the single-electron
reduction of nitrite catalysed by nitrite reductase where the type 2 copper site is involved in substrate binding.
The catalytic competence of the dinuclear copper site of Hc in redox reactions has been demonstrated also in
the case of hydrogen peroxide dismutation -  reaction that can be conveniently used to prepare the dinuclear
cupric derivative or met-Hc - and in the case of o-diphenol oxidation to quinines. The latter reaction, that is
typical for other dinuclear copper containing proteins tyrosinases and polyphenoloxidases, has been recently
interpreted as depending on low efficiency interactions between the o-diphenol substrate with the active site. The
equilibrium position of the protein-substrate interaction can be modified, hence increasing the efficiency of the
reaction, by introducing suitable conformation perturbants such as salts of the Hofmeister’s series, or by
proteolytic cleavage of the native protein that result in an increased accessibility of the active site.
The met-hemocyanin form, characterised by an EPR-silent [Cu(II) Cu(II)] site, is an important derivative for
defining the structural characteristics of the active site in the native protein and to diversify the chemical
reactivity of the two Cu-sites. The reaction of conversion of oxy-Hc to the met-derivative occurs spontaneously,
but very slowly; however it can be stimulated by various anions including fluoride, azide and acetate. The
18
proposed active site structure for the met-Hc form assumes a Cu(II) binuclear derivative having an di--hydroxo
bridge. A partial protonation of these bridges takes place at low pH. The fundamental question of the origin of the
diamagnetism in the met-hemocyanin form is still unresolved. Azide is the best suitable exogenous ligand for
probing the characteristics and accessibility of the active site in various met-Hc derivatives since, in coordinating
with Cu(II), azide produces a complex with a moderate absorption in the 350-440 nm range (~1500-2000 M1cm-1) caused by the LMCT transition N - to-Cu(IIhe characteristics of this transition (position and
3
intensity) are strongly dependent on the mode of coordination of the ligand anion. The absorption and CD LMCT
features of the azide-Cu(II) adduct allow to discriminate between terminal and bridging binding modes of the
ligand.
Concerning azide coordination, the Hc from the mollusc Octopus vulgaris and the arthropod Carcinus aestuarii
met-Hcs differ from each other, pointing to specific differences that depend on the phylum. The affinity towards
azide, the stoichiometry of binding, as well as its coordination mode show pH dependence. At pH 7.0, the same
1:1 stoichiometry of the azide adducts is exhibited by the two met-Hcs. However, the LMCT features in
absorption and CD spectra suggest that azide binds in a bridging mode in the case of Octopus met-Hc active site
in contrast to Carcinus met-Hc where azide binding, probably, occurs on the more exposed Cu(II) A centre in
terminal mode. The suggested greater rigidity of the active site in the arthropodan case as compared with the
molluscan met-Hc, may prevent the accommodation of azide as a bridging ligand inside the cavity containing the
active site. The stoichiometry of binding of the azide ligand between the proteins of two phyla differs at pH 5.5.
At this pH a second azide binds to Octopus met-Hc. The LMCT features in absorption and CD spectra are
indicative of a bridging binding mode for the first azide (with greater affinity compared to pH 7.0) and a terminal
binding mode for the second azide to copper (CuA) that controls the active site reactivity. The hemocyanin from
arthropod at pH 5.5 behaves differently and binds only one azide molecule. Assuming for both met-Hcs the same
bis-hydroxo adduct of the binuclear site, different reaction models for the binding of azide to Octopus and
Carcinus met-Hcs have been proposed.
High resolution Cu K-edge spectra provide a suitable tool to investigate the modifications of the coordination
geometry of either Cu(I) or Cu(II) in the active site that are expected for the proteins exhibiting different
reactivity. Two different approaches can be used in the analysis of the edge data: in a first one, is based on an
established empirical correlation between the spectroscopic features of the XANES spectra and the coordination
geometry of a large number of Cu(I) and Cu(II) complexes. A second approach for the analysis of the edge data
implies their simulation using ab-initio calculation programs that uses, as input, structural models. The
determination of the Cu-N bond length and the metal-metal distance are carried out by EXAFS spectroscopy.
Comparison between data of the Hcs derivatives and of the related model compounds, provide results that
support a description of the met derivatives as five-coordinated O-bridged dicopper(II) centre for the two
proteins. The hypothesis of a bis(hydroxo) structure for both species, with a Cu-Cu distance about 3 Å is the
favourite. The results obtained for the met-azido Hcs are compatible with the spectroscopic characterizations.
The -1,3 mode appears more probable supporting the results based on optical spectroscopy. The situation of
Carcinus derivative is more complex and less clear, however, a terminal mode seems more favourable.
The X-ray absorption spectroscopy techniques has been applied also for the characterization of the dinuclear
Cu(II)-peroxide site of oxy-Hc as well as of the dinuclear Cu(I) site of deoxy-Hc in a wide study aimed to
correlate the coordination geometry at the active site level with the oxygen binding properties of the protein. This
approach is particularly suited to study the Cu(I) complex of deoxy-Hc since it is devoid of optical properties and
the reported luminescence assigned to the Cu(I)-imidazole complex is not as well characterized as to allow for
structural resolution. Current knowledge on the biochemistry and the molecular physiology on Hcs indicate as
plausible structural modifications deriving from oxygen binding to the dinuclear centre of the individual subunits
or functional units: a) changes in bond length and coordination geometry for one or both the metal ions due to the
decrease in ionic radius and to the increase of charge on going from Cu(I) (r=0.96 Å) to Cu(II) (r=0.72 Å); b)
changes in the metal-metal distance; c) local conformational rearrangements of the active site region that change
the accessibility of the metal for oxygen due to a) and/or b). On these bases, we believe that it is of great interest
to verify if the same molecular mechanism can be used to describe the allosteric phenomenon observed in various
Hcs, deriving from different species, which show only a limited sequence homology.
The measurements require a controlled medium in order to avoid photoreduction of copper as it has been
successfully accomplished by embedding the protein in a sucrose matrix. Such method has been proposed of
general use for XAS spectroscopy on copper or iron proteins. Several arthropodan and molluscan hemocyanins
have been studied in order to trace the inter- and intra-phyla differences. The XANES spectra of oxyhemocyanins of the different species are remarkably similar, consistent with a very strongly conserved coordination geometry of the copper active site. In contrast, small but significant differences are observed between
the deoxy-forms of arthropodan and molluscan proteins. In particular, the XANES spectra of deoxy-arthropodan
hemocyanins (with the exception of L. polyphemus Hc) show a more intense edge feature at approximately 8983
eV. This difference is tentatively assigned to a more planar geometry of the copper-ligands system in the
19
arthropodan rather than in the molluscan proteins. The first shell analysis of the EXAFS modulation is consistent
with the presence of n = 3 N2 imidazole nitrogens at an average distance of 1.92±0.03 Å from copper in all the
deoxy-hemocyanins investigated. Binding of dioxygen results for all hemocyanins in the increase of the number
of first shell back-scattering atoms to n = 5 with average distances of 1.93 Å. Alternatively, by separating the
contribution of N2 imidazole nitrogens and of peroxide O-atoms, n = 3 ligands at 1.98±0.03 Å and n = 2 ligands
at 1.87±0.03 Å are found. These studies allow to propose that the different affinities for dioxygen are, at least in
part, due to peculiar differences of the deoxy-forms. The peroxide ligand in oxy-Hc represents a structural
constraint that normalizes the metal-ligand complex in the various Hcs.
Molecular heterogeneity and sovramolecular organization of hemocyanins and hemoglobins
Hemocyanins (Hcs) and invertebrate hemoglobins (Hbs) (including chlorocruorins) are giant molecules. The
aggregates that are found in vivo exhibit molecular weights ranging between 450 kDa and 9.0 MDa according to
the species. Such proteins have a very peculiar quaternary structure that can be described on the basis of
relatively simple models. Thus, molluscan Hcs are referred to as hollow cylinders with a 5- or 10- fold symmetry
axis. In cephalopods, the decamers are the only hemocyanin quaternary structure observed, but in gastropods two
decamers are assembled face-to-face to form the so-called di-decamer. The diameter of these molecules is 35 nm
and the height is 36 nm in gastropods and 18 nm in cephalopods. Upon increasing the pH in absence of divalent
cations all molluscan Hcs dissociate in subunits with sedimentation coefficient 11S and molecular weight range
between 250 and 450 kDa according to the species. Such subunits are folded as to form several globular
functional units (FUs), with a molecular mass of 45-65 kDa and each containing one active site. The structure at
15 Å resolution of the di-decamer of keyhole limpet hemocyanin isoform KLH1, the 2.3-Å resolution of the
tertiary structure of the C-terminal FU of Octopus dofleini Hc, the wealth of data from immunoelectron
microscopy, the 12-Å reconstruction of the quaternary structure of Haliotis tuberculata Hc and recent hypothesis
for evolution of the quaternary structure of molluscan Hcs, have increased the information about the exact
topological position of the various FUs types and the path of the subunits to form the hollow cylinders.
In a number of studies carried out at the CNR Centre we focused on the quaternary organization of molluscan
Hcs using two different approaches. The first one consisted in the kinetic and equilibrium study of molluscan Hc
dissociation, in order to obtain information on the hierarchical organization of the native molecules. For these
goals, light scattering stopped-flow -for kinetic measurements-, electron microscopy with negative staining and
small angle X-ray absorption techniques (SAXS) -for equilibrium measurements- has been applied. The latter
techniques have been conveniently implemented with image reconstruction methods and structural analysis
software for defining a structural model of the macromolecule. In particular, a technique for reconstructing iceembedded macromolecules from electron micrographs taken at two specimen tilts (+/-23 degrees) has been used
to determine the structure of chlorocruorin isolated from the Polychaete annelid Sabella spallanzanii. The
structure of this protein, essentially the same as that for Lumbricus terrestris is a bilayer structure with overall
symmetry D6, containing six hollow groups per layer. A hollow group is formed by six globular masses and has
approximate threefold symmetry. Other structural elements connect the two layers and the hollow groups in a
layer. This non-globin material occupies about 15% of the total molecular volume. The elaboration of SAXS data
is still in progress for both Hbs and Hcs and ultimately will allow for: the specification of the position of each
structural subunit within the oligomer (Hbs and Hcs), the role of water-protein interaction for the conformational
transition between the two functional states of the protein: oxy- and deoxy-Hc. Such kind of analysis has been
made very reliable in the recent years by the development of robust simulation algorithms that can approach the
problem starting from the crystallographic coordinates of the subunit or FU.
The second approach consists in the deconstruction of the native molecule to reduce complexity. Then, the
products to be studied are the structural subunits or the FUs that can be produced by chemical cleavage of
covalent bonds linking them together in the structural subunit. When the structural changes at the active site
levels, depending on oxygen coordination, could be related to the structural changes at the dimensional scale of
the whole molecule we will be able to trace the conformational demands that define the allosteric properties of
the oligomer. Furthermore the elucidation of the sequence of subunits or of FUs will allow to trace the
evolutionary pathways within each protein type.
The native form of hemocyanin (Hc) from Octopus vulgaris can be completely dissociated, at alkaline pH and
in the presence of EDTA, from 49S decamers to 11S monomers. The kinetics of this process shows that the
dissociation of decamers to monomers takes place in three consecutive and irreversible steps, with a highly
cooperative step concerning dissociation of octamers to dimers, which appears to be the only intermediate
species. From such structural units, the FUs can be obtained, on the basis of literature methods, by limited
proteolysis using suitable proteolytic enzymes. The current literature model for molluscan Hcs involve the
presence, within the structural subunit, of globular FUs, constituted about 400 amino acid residues that are
connected by portions of the polypeptide chain, consisting of 10-15 amino acid residues, more sensible to
proteases than the globular regions. The FUs are identified a-h, starting from the amino terminus of the subunits.
20
Limited proteolysis with -chimotrypsin of native Rapana venosa hemocyanin allows the separation of three
functional proteolytic fragments with molecular mass of  150, 100 and 50 kDa. The functional fragments,
purified by combining gel filtration and ionic exchange FPLCromatography, were analysed by means of small
angle X-ray scattering (SAXS). Independent shape determination of the 50 kDa and 100 kDa proteolytic
fragments yields consistent low-resolution models. A simultaneous fitting of the SAXS data from these fragments
provides a higher resolution model of the 100 kDa species made of two functional units tilted with respect to each
other. The model of the 150 kDa proteolytic fragment consistent with the SAXS data displays a linear chain-like
aggregation of the 50 kDa functional units. These observation provide valuable information for the reconstruction
of the three-dimensional structure of the minimal functional subunit of gastropod hemocyanin in solution.
Furthermore, the spatial relationships among the different functional units within the subunit will help the
elucidation of the overall quaternary structure of the oligomeric native protein. We have recently observed that by
Zn2+ treatment of the 11S structural subunit it is possible to obtain with high yield 50 kDa fragments that are
currently under investigation to compare their N-terminal sequences with those of the FUs produced by
proteolytic cleavage with the ultimate goal to identify the cleavage site and the reaction mechanism.
As outlined above, arthropod Hcs are refeered to a completely different organization plan. Native arthropod
Hcs are multimeric proteins where each subunit has a molecular mass of about 75 kDa (5S) and contains one
binuclear copper site capable of oxygen binding. Different functional subunits are arranged as hexamers (16S
corresponding to 16-mer or building block) or multiples of hexamers (24S, 36S, 48S and 62S corresponding to
2x6-mers, 4x6-mers, 6x6-mers and 8x6-mers, respectively). The native aggregation level appears to be
characteristic for each species and may also be related to the taxonomic groups. In the hemolymph of most
crustacea, hexamers (16S) or dodecamers (24S) or both are found. However, the biological significance of the
different aggregation states is still controversial. Although most arthropod Hcs exhibit only one or two
aggregation states in vivo, it is usually possible to obtain dissociation to the lower structure by a proper choice of
non-physiological solution conditions. In particular, removal of divalent cations (Ca ++, Mg++) by dialysis against
EDTA and/or a change of the pH value from the neutral range will cause dissociation, which in many cases is
reversible.
An interesting feature of the arthropod Hcs is their marked heterogeneity at the subunit level. Such
heterogeneity derives from both differences in amino acid composition and molecular weights. These types of
differences have been observed in all arthropod Hcs with a possible exception for the polypeptide chain
composition of the 16S hexameric components of some isopods. Generally the assembly of the higher di- tetrahexa- and octa-hexameric hierarchies found in various crustacean, chelicerate and centipede Hcs, requires a large
number of different subunits. In fact, while a single type of subunit appears to be adequate for the correct
reassembly of the basic hexameric unit, certain key bridging or “linker” subunits are necessary for the formation
of higher assemblies, larger than hexamers. Different subunits occupy specific locations within the oligomeric
structure and are generally present in constant proportions. Furthermore, the total set of subunits is required to
reorganize the original aggregate from a mixture of dissociated products, indicating that each of them plays a
specific role in the architecture of the protein. This is indicated by the fact, that purified subunits often possess
the ability to assemble into homohexamers, but heterogeneity is necessary for the correct assembly of the native
quaternary structure. Subunit heterogeneity has functional role in the modulation of the oxygen binding
properties of Hcs; in particular, it seems to be required for the adaptation of organisms in response to changes of
the environmental conditions. There is evidence that in some Crustacea Hc, the subunit composition varies with
season, oxygen level, or salinity, which results in a modulation of the functional properties. Furthermore, it has
been shown that the polymorphism is not genetically fixed and, in relation to this, changes in structural and
functional phenotypes of Hc in response to specific environmental stimuli have been observed.
The oxygen binding properties of arthropod Hcs have a significant dependence on pH, concentrations of
specific ions and other allosteric effectors. The p50 values vary widely, reflecting the wide variety of
environmental conditions and behavioural patterns observed for different organisms. The degree of cooperativity
for oxygen binding also shows a wide range of variation and is generally greater in Hcs containing larger number
of subunits. On these grounds we have studied the molecular heterogeneity of a number of crustacean Hcs
isolated from species that inhabit peculiar areas or exhibit peculiar physiological responses to the environmental
stimuli. The strategy behind these studies is to characterize the subunit pattern of a given crustacean Hc and to
correlate it with the allosteric properties exhibited in oxygen binding. This approach provides the information
necessary to evaluate the changes at molecular level that are induced from a modification of environmental
parameters.
As described above for Hcs, also the annelid Hbs are organized in a very complex sovramolecular network of
interacting polypeptides, the structure of which is still not wholly resolved. We were able to separate by twodimensional electrophoresis the 4-MDa chlorocruorin of Sabella spallanzanii and identify its components by
amino-terminal sequencing. This approach revealed a high heterogeneity of constituent chains in a single animal
as well as in the Sabella population. Using a cDNA library prepared from the haematopoietic tissue of this worm,
21
we have isolated and fully sequenced most globin and linker cDNAs. The primary structure features of these
polypeptides have been characterized by comparison with model globin and linker sequences.
The evolution of extracellular hemoglobins of annelids, vestimentiferans, and pogonophorans was then
investigated by applying cladistic and distance-based approaches to reconstruct the phylogenetic relationships of
this group of respiratory pigments. We performed this study using the aligned sequences of globin and linker
chains that are the constituents of these complex molecules. Our results allowed us to test previous hypotheses on
the evolutionary pathways of these proteins and to formulate a new most parsimonious model of molecular
evolution. According to this novel model, the genes coding for the polypeptides forming these composite
molecules were already present in the common ancestor of annelids, vestimentiferans, and pogonophorans.
22
4. PHOTOSENSITIZING AND PHOTOTHERAPEUTIC
PROPERTIES OF PORPHYRINS AND THEIR ANALOGUES
The phototoactivation of porphyrins and their analogues, which posses a tetrapyrrolic macrocycle (chlorins,
porphycenes, purpurins, phthalocyanines and naphthalocyanines), is a research area of increasing interest. The
photobiological properties of such compounds are the basis for the development of a variety of applications
ranging from basic research to biotechnologies. Such applications include:
 the conversion of solar energy into chemical energy by artificial systems mimicking the natural photosynthetic
apparatus;

mapping the microenvironment of porphyrin-type prosthetic groups in proteins
 the controlled generation of reactive oxygen species with an aim to study their physico-chemical properties in
homogeneous and microheterogeneous biological systems;
 the promotion of photobiostimulation and photosignalling processes starting from predetermined studies where
the incident photons are piloted, e.g. the onset of apoptotic processes, the induction of focalized mutations and
the activation of specific enzymic functions;
 the development of phototherapeutic techniques, mainly in oncology (photodynamic therapy of tumours), as
well as in dermatology (phototherapy of psoriasis and actinic keratosis), atherosclerosis (prevention of artery
restenosis after balloon angioplasty), and the sterilization of viral and microbial infections.
This wide range of applications is related with the possibility to chemically synthesize porphyrin derivatives
with a fine-tuned chemical structure; this allows the modulation of their physico-chemical properties and their
distribution pattern at a cell/tissue level. The importance of such modulation arises from the short lifetime of the
photogenerated reactive species, so that the porphyrin-promoted photoprocesses take place in a restricted (a few
nm) spatial range around the porphyrin binding site. The variation of the chemical structure of porphyrins is
achieved through the control of:
 the extension of the tetrapyrrolic macrocycle;

the nature of the peripheral substituents;

the presence of metal ions coordinated with the pyrrolic nitrogens;

the nature of the axial ligands to the metal ions.
In general, our research line is developed according to the following steps:
a.
chemical synthesis of porphyrins with predetermined chemical structure
b.
spectroscopic characterization of the porphyrins in their ground and electronically excited states
c.
determination of the quantum yield of the photogeneration of reactive intermediates
d. photokinetic study of the photosensitized modification of model biomolecules (e.g. steroids, unsaturated
lipids, aromatic amino acids)
e.
affinity of individual porphyrins for non-transformed, tumour, microbial cells and determination of
dark cytotoxicity and subcellular distribution
their
f. kinetics and mechanism of porphyrin-sensitized cell photoinactivation and correlation with the subcellular
distribution.
g. pharmacokinetic and photosensitizing properties of porphyrins in vivo
h.
applications of porphyrin-photosensitised processes for the photodynamic therapy of tumours and other
diseases
23
Main Results
a) Synthesis of Porphyrinoids
As mentioned in the introductory paragraph several approaches are available in order to engineer porphyrin
molecules with different chemical structure, hence with predetermined physico-chemical properties. In our
investigations we were mostly interested in porphyrin derivatives having an extended aromatic conjugation in
order to shift the absorption spectrum toward the far-red/near-IR wavelength region which is of high interest for
medical applications. Thus, we prepared the following porphyrinoids with an extended macrocycle: porphycenes,
which represent electronic isomers of porphyrins with a 18 electron cloud; chlorines, which are characterized by
the reduction via hydrogenation of one pyrrole ring; phthalocyanines and naphthalocyanines, where a benzene
and, respectively, a naphthalene ring is condensed with each pyrrole moiety.
Moreover, for each class of compounds, we used both the free base and selected metallo-derivatives: several
metal ions can be coordinated at the centre of the macrocycle, however only diamagnetic ions are of interest for
photobiological applications; therefore, we prepared porphyrinoid derivatives with Mg(II), Zn(II), Al(III),
Ge(IV), Si(IV) and Sn(IV). In a few cases, axial ligands were placed in the fifth and sixth coordination positions
of the central metal ion as an additional tool to modulate the physico-chemical and (photo)biological features of
the porphyrinoid molecules.
Lastly, we focused our attention on porphyrinoids substituted in the peripheral positions of the macrocycle by
functional groups with well defined chemical structure, in order to generate compounds differing in size, electric
charge, hydrophilic or hydrophobic character, and bulkiness. Typical examples are represented by polycarboxylated or poly-sulphonated derivatives, alcoholic groups linked to the pyrroles via hydrocarbon chains of
different length, aliphatic amino groups or pyridine/piperidine rings with both tertiary or quaternary nitrogen
atoms, etc.
All the compounds were analysed for their chemical purity by thin layer chromatography or HPLC techniques,
as well as characterized by absorption and NMR spectroscopy. The various derivatives were also studied for their
chemical stability in the dark and under visible light-illumination both in the solid state and in solution. In
general, porphyrins and their analogues display an excellent chemical stability and a longer shelf life.
b) Spectroscopic characterization
As a rule the porphyrin derivatives synthesized by us displayed absorption bands peaking at longer wavelengths
and possessing larger molar extinction coefficients as compared with porphyrins. Such spectroscopic properties
were important since they guaranteed a higher probability and efficiency of light absorption, hence of generation
of electronically excited states. The absorption spectra of the various porphyrins were monitored as a function of
the porphyrin concentration in order to define the molarity range where the Beer-Lambert law was strictly
followed, thus allowing us to identify the conditions corresponding to a purely monomeric state of the porphyrin;
in actual fact, as outlined below, aggregated porphyrins are most frequently characterized by a poor
photosensitising activity.
The aggregation of porphyrins, which reflects the tendency of the flat tetrapyrrolic macrocycle to yield face-toface dimers or higher oligomers due to hydrophobic interactions, is more pronounced in aqueous media, while its
importance decreases upon moving to organic solvents or micellar/liposomal dispersions of surfactants and
phospholipids. Porphyrins undergo a ready partitioning into the non polar section of micelles and liposomes.
The absorption spectroscopic studies were integrated by fluorescence excitation and emission measurements,
which were performed under both steady-state and time-resolved conditions. Such measurements would yield
important information on two main aspects:
1) The quantum yield of fluorescence emission, which indicates the probability of radiative decay of the
porphyrins from the initially formed lowest excited singlet state; such emission is often used in biological
systems for a quantitative determination of the porphyrin concentration, as well as for probing the nature of
porphyrin microenvironment and binding site in a cell or tissue.
2) The presence of multiple porphyrin species, for example a mixture of monomeric and aggregated porphyrins:
the porphyrin aggregates generally exhibit a reduced fluorescence quantum yield, and a shorter emission lifetime;
if the fluorescence decay is monitored according to a time-resolved regime, one can obtain a quantitative
measurement of the relative weight of each porphyrin species. Determining the amount of aggregated species has
also a predictive role for the photosensitising efficiency of porphyrins. In general, the quantum yield of porphyrin
fluorescence emission does not exceed 0.2 and in many cases is below 0.1. This value points out that a
predominant fraction of the electronically excited porphyrin molecules undergo intersystem crossing to the
lowest excited triplet state: the latter plays a major role in porphyrin-photosensitized processes owing to its
particularly long lifetime (of the order of milliseconds) even in fluid media.
24
c) Photogeneration of reactive intermediates
As mentioned in the previous paragraph, the lowest excited triplet state represents the main reactive
intermediate in photosensitised processes promoted by porphyrins and their anlogues. The efficiency for the
generation of such electronically excited state can be quantitatively measured through a specific parameter, the
quantum yield, which is the ratio between the number of triplet species formed vs. the total number of
photoexcited photosensitiser molecules. This parameter can be obtained by means of laser flash photolysis
techniques with a resolution level of microseconds. In general, both free base and metallo-porphyrinoids
coordinated with diamagnetic metal ions exhibit quantum yields for triplet photogeneration higher than 0.5; such
a value underlines the appreciable overall photosensitising efficiency of these tetrapyrrolic derivatives. The
lifetime of porphyrin triplet states is in the millisecond range, which gives these species a high probability to
diffuse over relatively large distances in fluid media.
In actual fact, two reaction pathways are open to triplet porphyrins:
1) the direct interaction with a nearby substrate molecule with formation of radical derivatives, which in turn
react with oxygen to yield oxidized products;
2) energy transfer to oxygen with promotion of the latter to singlet oxygen, a hyper-reactive and highly cytotoxic
species.
While in principle both mechanisms occur in porphyrin-sensitised photoprocesses, the singlet oxygen pathway
usually predominates especially in hydrophobic media (e.g. organic solvents of low dielectric constant, internal
regions of globular protein molecules, lipid domains of cell membranes) where the oxygen concentration is
particularly large and the singlet oxygen lifetime is longer. This feature allows one to classify porphyrinoid
compounds as typical “photodynamic” sensitisers (i.e. oxygen-requiring photosensitisers).
Two factors may inhibit the photosensitising action of porphyrins, namely (1) the formation of aggregated
species (which most frequently occurs in aqueous media) owing to the related drop in the lifetime of the triplet
state; and (2) the insertion of paramagnetic metal ions (e.g., Fe (III), Co(III) ions) at the centre of the macrocycle:
such derivatives posses a quantum yield of triplet generation close to unity, however the triplet leifetime falls
below the nanosecond level thereby preventing any interaction between the triplet and other molecules.
Lastly, we ascertained that photoexcited porphyrins may also generate syperoxide anion via electron transfer to
oxygen. However, the efficiency of this process is about 1% that typical of singlet oxygen generation,hence
superoxide hardly plays any important role in porphyrin-photosensitised processes.
d) Photosensitised modification of model biomolecules
Preliminary studies demonstrated that the following biomolecules are most readily susceptible to
photooxidative attack sensitised by porphyrins and their analogues:
- Aromatic and sulfur-containing amino acids, such as tryptophan, histidine, tyrosine, cysteine and methionine.
- Unsaturated lipids and steroids, including cholesterol
- Guanosine nucleotides
On these bases we selected both tryptophan, in the form of N-acetyl-L-tryptophanamide
(NATA) and cholesterol as model substrates for testing the photosensitising efficiency of the
various porphyrinoids. In all cases, the two substrates were photomodified according to first order kinetics: the
efficiency of the photoprocesses can be determined via the frist order rate constant of the semilog plot: [substrate]
vs. irradiation time. Tryptophan photooxidation, leading to the formation of an oxidised derivative, namely Nformyl-kynurenine, occurred with k = 105 s-1, which is in line with highly efficient photodynamic sensitisers. This
conclusion was further supported by the data on cholesterol photooxidative conversion to its 5- and 7hydroperoxides, which occurred with k = 104 s-1. As expected, such photoprocesses were found to be most
efficient in lipophilic microenvironments: typical examples are represented by liposomal vesicles where the
porphyrinoid molecules are embedded in the phospholipid bilayer or non-covalent complexes between the
porhyrinoids and lipoproteins where the porphyrin is partitioned within the large lipid moiety.
e) Binding of porphyrins to eukaryotic and prokaryotic cells
The affinity of porphyrinoids for essentially all types of cells is strongly influenced by their chemical structure.
Thus, in the case of mammalian cells, including normal and transformed fibroblasts, amelanotic and melanotic
melanoma cells and keratinocytes, maximum accumulation was obtained by using lipophilic and amphiphilic
derivatives: for example, porphyrins bearing two to eight phenyl rings or ester functions as peripheral
substituents, or porphyrins bearing two carboxylate groups on adjacent pyrrole rings. In general, the kinetics of
porphyrin uptake by mammalian cells is rather slow, with significant endocellular concentrations reached after 23 h incubation.
The incubation time also affects the pattern of subcellular distribution of the porhyrins: thus, the cytoplasmic
membrane represents the most important binding site for short (no longer than 1-3 h) incubations; prolonging the
25
incubation time favours a redistribution of the porphyrins to endocellular membranous compartments, including
mitochondria, lysosomes, the Golgi apparatus and the rough endoplasmic reticulum. This pattern is also
dependent on the delivery system adopted for the administration of hydrophobic porphyrinoids to cell cultures:
thus, preincorporation of the porphyrins in liposomes or low-density lipoproteins (LDL) promotes endocytotic
processes with a release of the photosensitiser to endocellular sites. The porphyrin delivery via LDL is of
particular interest in the case of tumour or other kinds of rapidly proliferating cells, which are usually
characterized by an overexpression of LDL-specific receptors; as a consequence, the administration of the
porphyrin by this route leads to a selective or at least preferential accumulation of the photosensitiser in
neoplastic as compared with normal cells.
An essentially identical picture was obtained upon studying the accumulation and subcellular partitioning of
porphyrins in yeast cells, such as Candida albicans, as well as in prokaryotic cells, such as Gram-positive
bacteria. It was found that amphiphilic porphyrins readily cross the outer wall surrounding the plasma membrane
and localise in large amounts at the level of specific protein constituents of the membrane. the rate and extent of
porphyrin accumulation can be modulated to some degree by controlling the amount of cholesterol in the
membrane, Increasing such paarmeter causes an increased membrane rigidity and a less pronounced overall
uptake of the porphyrinoid molecules. Thus, the cytoplasmic membrane again appears to represent the main
binding site in such cells.
A somewhat different picture was observed in the case of Gram-negative bacteria: these cells are characterized
by the presence of a highly organized outer wall, which can efficiently intercept the externally added
photosensitiser molecules. Only upon enhancing the permeability of the wall was a signifcant amount of
porphyrinods accumulated at the level of the plasma membrane in typical Gram-negative bacterial strains, such as
Escherichia coli or Pseudomonas aeruginosa. The permeabilization was obtained by addition of EDTA, which
chelates some Ca2+ counterions neutralizing the negatively charged groups at the surface of the outer wall of
these bacteria, or peptide-type agents, such as polymixin or polylysine. Quite interestingly, no difference in the
rate and extent of porphyrinoid accumulation was detected between wild-type and antibiotic-resistant strains,
including methycillin- and vancomycin-resistant strains of Staphylocccus aureus or multidrug resistant
Pseudomonas aeruginosa. This observation opens the way to the use of photodynamic processes as a tool for the
inactivation of antibiotic-resistant microbial pathogens.
In no case, detectable amounts of porphyrinoid derivatives were found to bind with the DNA or other genetic
material in both prokaryotic and eukaryotic cells. As discussed more in detail in a later paragraph, this
circumstance decreases the probability that nuclear damage plays a major role in photosensitised inactivation of
cells, thereby minimizing the risk of inducing the onset of mutagenic or cancerogenic processes in partially
inactivated cells.
Porphyrin-loaded mammalian and bacterial cells underwent no detectable toxic effect when incubated in the
presence of porphyrin concentrations lower than 10 M; such concentrations are most efficient in inducing
photochemical damage to cells. Dark toxicity is only observed for porphyrinoid concentrations larger than 25-30
M. Therefore, a suitable choice of the experimental parameters, such as the porphyrinoid dose and the preirradiation incubation time, allows one to avoid any generalized toxic effects and focus the photosensitised
process within the illuminated area. This feature represents the basis for the application of porphyrinoidphotosensitised processes in medical fields, as discussed below.
f) Porphyrin-photosensitised inactivation of mammalian and microbial cells
Irradiation of porphyrinoid-loaded cells with light specifically absorbed by the photosensitising agent
invariably results in the damage of subcellular sites surrounding the porphyrinoid binding sites. The overall
photoprocess is characterized by a high degree of selecitivity owing to the very short lifetime and high reactivity
of the phototoxic intermediate species. As a consequence, in the case of mammalian cells, the most readily
damaged sites are represented by the cell membranes in agreement with the above detailed pattern of subcellular
distribution typical of porphyrins and their analogues. In particular, the photodamage is restricted within the
plasma membrane for irradiations performed after relatively short incubation times (1-3 h), while as the
incubation is prolonged inner membranous districts are more heavily involved in the photoprocess. In this
connection, some “fine tuning” of the photodamaged sites can be achieved by selecting the chemical structure of
the porphyrinoid photosensitiser: thus, cationic derivatives preferentially affect the mitochondrial membrane,
while hydrophobic (liposome-delivered) porphyrins largely affect the lysosomal bag.
The photosensitised and photodamaged cells exhibit some tendency to promote repair processes, largely
through the expression of stress proteins. However, in most cases, cell death represents the obvious consequence
of the photoprocess: the death can occur via either random necrosis or apoptosis; the relative weight of the two
modalities of cell death is controlled by a variety of factors, whose precise role has not yet been determined.
Present evidence suggests that apoptosis is favoured by mild irradiation conditions and by the use of
mitochondria-bound porphyrins which induce the inactivation of the antiapoptotic protein Bcl-2.
26
Depending on the distribution pattern of the porphyrinoid photosensitiser, the biological consequences of the
photoprocess include the impairment of transmembrane transport of metabolites, drop in specific enzymic
activites, alteration of membrane potential, cross-linking of membrane or cytoplasmic proteins etc. In any case,
nuclear damage takes place only after prolonged irradiation and is not correlated with cell death. The latter event
is rather a consequence of osmotic unbalance and inhibition of ATP synthesis.
As regards the microbial cells, an extensive (5-6 log) decrease in the population of living cells is generally
obtained by using markedly milder irradiation conditions as compared with mammalian cells: thus,
photosensitised killing of such cells is very effective already after 1 min incubation with porphyrinoid
concentrations as low as 0.1 M, which are ineffective toward mammalian cells. This feature is extremely
important for possible phototherapeutic applications of these photoprocesses to treat microbial infections, since it
guarantees a high degree of selectivity toward the microbial pathogens in comparison with host tissues. Once
again, the photoinduced damage is largely limited to the plasma membrane with no significant involvement of the
genetic material: no evidence for mutagenicity or repair of the photodamage has been obtained with all the
bacterial and yeast strains investigated by us.
g) Pharmacokinetic and photosensitisation studies in experimental animals
The possibility to use porphyrin-photosensitized processes for the so called photodynamic therapy (PDT) of
tumours was preliminarily investigated in tumour-bearing mice. Two main tumour models were used, namely
MS-2 fibrosarcoma intramuscularly transplanted in Balb/c mice and B16 melanotic melanoma subcutaneously
transplanted in C57 mice. The use of PDT is based on the assumption that the photosensitising agent is
selectively or preferentially accumulated in the neoplastic lesion so that the photodamage induced by irradiation
with light wavelengths specifically absorbed by the photosensitizer is confined in the diseased tissue. To achieve
this goal the porphyrins or their derivatives need to be transported by serum LDL , which express a preferential
interaction with tumours cells via receptor-mediated endocytosis. The porphyrins with higher affinity for tumours
are actually characterized by a large degree of hydrophobicity: the latter parameter is measured in terms of
partition coefficient of the photosensitizer between n-octanol and water; partition values higher than about 10 are
typical of tumour-selective porphyrins. The porphyrins are intravenously administered after incorporation into
liposomal vesicles, which are engineered in such way to promote their extremely rapid fusion with LDL, thereby
releasing the photosensitizer to the lipoprotein. A rigorous control of the transport modality of the systemically
injected porphyrin yields photosensitizer concentration ratios as high as 20 between the tumour and the
peritumoural districts.
In general, the maximum concentration of porphyrin-type photosensitizers in the tumour tissues is reached
within 24 h from injection; however, the clearance form the tumour is generally slow so that significant
concentrations of hydrophobic porphyrins in the neoplastic tissue are preserved for at least 72 h. The porphyrin
molecules localize inside the neoplastic cells with only minor concentrations in the neovascular network. As a
consequence, upon irradiation of the tumour area, a direct killing of neoplastic cells is obtained with only minor
vascular damage; this ensures a sufficiently large supply of oxygen to the irradiated tissue, minimizing the risk of
formation of hypoxic clusters, from which recurrencies most frequently originate. The irreversible damage of the
tumour takes place by both random necrotic and apoptotic pathways, analogously with what observed for
photosensitised cells. While the fibrosarcoma is efficiently phototreated by using both porphyrins and their farred absorbing analogues (chlorins, phthalocyanines), the pigmented melanoma can be successfully
photosensitised only by using compounds, such as naphthalocyanines, which exhibit intense absorption bands in
the wavelength region above 800 nm, where the residual absorbance by melanin is of minor importance.
The understanding of the modalities by which porphyrinoids are transported in the bloodstream, interact with
rapidly proliferating or normal cells, and photosensitize cell damage opened the way to the PDT of diseases
which are outside the oncological field. This area of research is steadily expanding. In our laboratory we started
two new phototherapeutic applications:
1. The treatment of occluded arteries after balloon angioplasty in order to prevent the occurrence of restenosis.
This technique involves the local delivery of the photosensitizer in the lesioned arterial segment followed by
irradiation with specific light wavelengths, which are piloted to the irradiation site via optical fibres connected
with a laser source. So far a preclinical PDT protocol has been developed through studies carried out on
rabbits whose arteries were opened by angioplasty and subsequently subjected to photosensitization. The best
results were obtained by using a Zn(II)-phthalocyanine delivered via a specifically built catheter: the
photoprocess brings about a selective destruction of smooth muscle cells, which are usually responsible for
the restenosis. The photodamage is confined to the intimal layers with no appreciable involvement of the
media and adventitia.
2. The treatment of microbial infections, especially those chronicized after antibiotic therapy. As a matter of
fact, porphyrinoid photosensitizers are just about as active against normal and antibiotic-resistant microbial
strains. Once again the most promising results have been obtained by using phthalocyanine-type
photosensitizers, which promote the photoinactivation of Gram(+) and Gram(-) bacteria, yeasts, fungi and
27
micoplasmas by using just one mild irradiation protocol. In vivo studies with artificially infected mice or
spontaneously infected dogs and cats clearly indicate that an extensive decrease in the microbial population
can be achieved with a minimal parallel damage to different types of host tissues.
h) Phototherapeutic applications at a clinical level
The experience accumulated through years of research activity in the field of PDT allowed us to establish active
and continuative collaborations with selected clinical centres for the treatment of specific diseases. Our group is
involved in monitoring the pharmacokinetic behaviour of the systemically injected or topically administered
photosensitizers, the definition of the clearance rate from blood and diseased tissues, the validation of any
variations in the standard clinical protocols.
In particular, our activity is focused in the PDT of the following pathologies:
- solid tumours of the breast, brain and skin (particularly successful is the treatment of AIDS-related Kaposi
sarcoma)
- recurrencies from surgically or radiotherapeutically treated melanotic melanoma
- infections of skin and burns caused by Staphylococcus aureus , including its methicillin-resistant strain
- stimulation of wound healing by sterilization of the intralesional bacterial flora
- treatment of periodontal and other oral cavity diseases caused by Candida albicans or bacterial agents.
28
PUBLICATIONS (1970 – 2001)
(1970)
ALBERGONI, V., CASSINI, A., SALVATO, B.
Ricerche sulle Emocianine. XIII. Isolamento e analisi di alcune frazioni glicopeptidiche dell`emocianina di
Octopus vulgaris.
Boll. Soc. Ital. Biol. Sper., 46, 939 (1970).
SALVATO, B., GHIRETTI-MAGALDI, A., ALBERGONI, V.
Ricerche le Emocianine. XIV. Terminali amminici delle emocianine di Octopus vulgaris e di Carcinus maenas.
Boll. Soc. Ital. Biol. Sper., 46, 943 (1970).
SALVATO, B., GHIRETTI-MAGALDI, A., TALLANDINI, L.
Ricerche sulle Emocianine. XV. Titolazione acido-base dell’emocianina di Octopus vulgaris.
Boll. Soc. Ital. Biol. Sper., 46, 961-964 (1970).
(1971)
SALVATO, B., SARTORE, S., ZACCARIA, C., GHIRETTI-MAGALDI, A.
Ricerche sulle emocianine. XIX. Peso molecolare delle subunità funzionali e delle catene polipeptidiche delle
emocianine di Octopus vulgaris.
Boll. Soc. Ital. Biol. Sper., 47, 777 (1971).
SALVATO, B., TALLANDINI, L., GHIRETTI-MAGALDI, A., GHIRETTI, F.
Ricerche sulle emocianine. XVII. Variazioni conformazionali dell’emocianina di Octopus vulgaris.
Boll. Soc. Ital. Biol. Sper., 47, 773-774 (1971).
SALVATO, B., TALLANDINI, L., GHIRETTI-MAGALDI, A., GHIRETTI, F.
Ricerche sulle emocianine. XVIII. Titolazione spettrofotometrica delle tirosine nell’emocianina di Octopus
vulgaris in presenza di tiourea e di tiocianato.
Boll. Soc. Ital. Biol. Sper., 47, 775-776 (1971).
(1972)
ALBERGONI, V., CASSINI, A., SALVATO, B.
The carbohydrate portions of hemocyanin from Octopus vulgaris.
Comp. Biochem. Physiol., 418, 445 (1972).
GHIRETTI, F., SALVATO, B., CARLUCCI, S., DE PIERI, R.
Manganese in Pinna nobilis.
Experientia, 28, 232(1972).
SALVATO, B.
Ricerche sulle Emocianine.XXII. Perfezionamento del metodo ditisone per la determinazione del rame.
Boll. Soc. Ital. Biol. Sper., 48, 1314 (1972).
SALVATO, B., SARTORE, S., RIZZOTTI, N., GHIRETTI-MAGALDI, A.
Molecular weight determination of polypeptide chains of molluscan and
arthropod hemocyanins.
FEBS Letters, 22, 5 (1972).
SALVATO B., GHIRETTI-MAGALDI A., ZATTA P., GHIRETTI F.
Ricerche sulle Emocianine. XXI. Titolazione acido-base della emocianina di Octopus vulgaris in soluzione di
3urea e guanidina.
Boll. Soc. Ital. Biol. Sper., 48, 1312 (1972).
SALVATO, B., ZATTA, P.
Ricerche sulle Emocianine. XX. Esclusione degli -NH2 terminali dal sito attivo dell`emocianina.
Boll. Soc. Ital. Biol. Sper., 48, 1311 (1972).
(1973)
GHIRETTI, F., GHIRETTI-MAGALDI, A., SALVATO, B.
The chemical basis for the evolution of hemocyanins.
In: Comparative Physiology (Bolis, L. et al., eds.) North Holland
Pbublishing, Amsterdam, p. 509 (1973).
SALVATO, B.
Ricerche sulle emocianine. XXII: Perfezionamento del metodo dei ditizone
per la determinazione dei rame.
Boll. Soc. Ital. Biol. Sper., 48, 1315 (1973).
GHIRETTI-MAGALDI, A., GHIRETTI, F., SALVATO, B.
The chemical basis of Hemocyanins.
29
In: Comparative Physiology. (L.Bolis et al. Eds.) 1973, p. 509.
GHIRETTI, F., GHIRETTI-MAGALDI, A.
Respiratory proteins in Molluscs.
In: Chemical Zoology(Florkin,M.,ed.) Acad. Press,Vol.VII,p.201 (1973).
GHIRETTI-MAGALDI, A., MILANESI, C., SALVATO, B.
Ricerche sulle emocianine. XXIII: I cianoblasti e i cianociti nei tessuti
emopoietici di Carcinus maenas.
Boll. Soc. It. Biol. Sper., 48, 1316 (1973).
GHIRETTI-MAGALDI, A., MILANESI, C., SALVATO, B.
Ricerche sulle emocianine. XXIV: Identificazione della proteina nei
cianoblasti e nei cianociti di Carcinus maenas.
Boll. Soc. It. Biol. Sper., 48, 1318 (1973).
GHIRETTI-MAGALDI, A., MILANESI, C., SALVATO, B.
Identification of hemocyanin in the cyanocytes of Carcinus
maenas.
Experientia, 29, 1265 (1973).
SALVATO, B.
Ricerche sulle emocianine. XXII: Perfezionamento del metodo dei ditizone
per la determinazione dei rame.
Boll. Soc. Ital. Biol. Sper., 48, 1315 (1973).
SALVATO, B., ZATTA, P., GHIRETTI-MAGALDI, A., GHIRETTI, F.
On the active site of Hemocyanin.
FEBS Lett., 32, 35 (1973).
SALVATO, B., TAMBURRO, G.A., GHIRETTI-MAGALDI, A.
On the active site of Hemocyanins.
IX Intern. Congress Biochemistry, Stockholm, p. 112, 2sll (1973).
SALVATO, B., ZATTA, P.
Ricerche sulle emocianine. XX:Esclusione dei gruppi NH2 dal sito attivo dell’emocianina di Octopus vulgaris.
Boll. Soc. Ital. Biol. Sper., 48, 1311 (1973).
SALVATO, B., ZATTA, P., GHIRETTI-MAGALDI, A., GHIRETTI, F.
Ricerche sulle emocianine. XX: Titolazione acido-base dell’emocianina di Octopus vulgaris in presenza di urea e
guanidina.
Boll. Soc. Ital. Biol. Sper., 48, 1312 (1973).
(1974)
ALBERGONI, V.
Ricerche sul metabolismo dei rame.
Arch. Fisiol.,71, 1 (1974).
ALBERGONI, V., CASSINI, A.
A cupro-zinc protein with superoxide dismutase activity from liver.
Comp. Biochem. Physiol., 47B, 767 (1974).
ALBERGONI, V., COBELLI, C., FRANCINI, G.L.
Biological Systems.
Pitagora Editrice, Bologna (1974).
FINAZZI-AGRO’, A., ALBERGONI, V., CASSINI, A.
Intrinsic fluorescence of a protein devoid of tyrosirie and tryptophan:
horse hepatocuprein.
FEBS Lett., 39, 164 (1974).
GHIRETTI, F.
L’evoluzione a livello molecolare. In: Le basi biologiche della Medicina moderna,
Edizioni Medico Scientifiche, Torino, Vol. 1, p. 215 (1974).
SALVATO, B., GHIRETTI-MAGALDI, A., GHIRETTI, F.
Acid-base titration of the hemocyanin from Octopus vulgaris.
Biochemistry, 13, 4778 (1974).
(1975)
ALBERGONI, V., CASSINI, A.
Superoxide-dismutase in Euglena gracilis.
Gior. Bot. Ital., 109, 160 (1975).
ALBERGONI, V., CASSINI, A.
The oxidation of cysteine by ceruloplasmin.
30
FEBS Lett., 55, 261 (1975).
ALBERGONI, V., CASSINI, A., FAVERO, N., ROCCO, G.P.
Effect of penicillamine on some metals and metallo—proteins in the rat.
Biochem. Pharmacol., 24, 1131 (1975).
GHIRETTI, F., GHIRETTI-MAGALDI, A.
Respiration. In: Pulmonates (Fretter, ed.) Vol. I, Acad. Press (1975).
GHIRETTI-MAGALDI, A.
Biosintesi in vivo dell’emocianina. Identificazione dei cianoblasti e dei cianociti in Carcinus maenas.
Atti V Congr. Soc. It. Biologia Marina, Tip. Ed. Salentina (1975).
JORI, C.
Photosensitized reactions of’amino acids and proteins.
Photochem. Photobiol., 21, 463—467 (1975).
TALLANDINI, L., SALVATO, B., JORI, G.
Photochemical effects associated with the copper absorption bands of the native hemocyanin from Octopus
vulgaris.
FEBS Lett.,54, 283-285 (1975)
ZATTA, P., VESSEY, D.A., ZAKIM, D.
The transfer of galactose from UDP-Calactose to endogenous lipid acceptor in liver microsomes.
Biochim. Biophys. Acta, 392, 361 (1975).
(1976)
COLAUTTI, P., MOSCHINI, C., STIEVANO, B.M., TRECNAGHI, C., JORI, C.
A study of gamma and neutron interaction with aqueous solutions of L-phenylalanine.
J. Radioanal. Chem., 34, 9-17 (1976).
GHIRETTI-MAGALDI, A., TAMINO, G., SALVATO, B.
The monophyletic origin of hemocyanins on the basis of the amino acid composition. Structural implications.
Boll. Zool., 42, 167 (1976).
SALVATO, B., JORI, C.
A fluorescence study of the copper-protein ceruloplasmin.
Bull. Mol. Biol. Med., 1, 97 (1976).
TAMBURRO, A.M., SALVATO, B., ZATTA, P.
A circular dichroism study of some hemocyanins.
Comp. Biochem. Physiol., 55, 347 (1976).
ZATTA, P.
Heavy metal hydrolisis of poly-isopranoid-phosphate mono and al igosaccarides.
Experientia, 32, 693 (1976).
ZATTA, P., VESSEY,. D.A.
Resolution of endogenous lipid intermediates of glycoproteins synthesis in liver microsomes.
Fed. Proc., 35, 948 (1976).
ZATTA, P., ZAKIM, D., VESSEY, D.A.
Incorporation of N-Acetylglucosamine into lipid linked oligosaccarides.
Biochim. Biophys. Res. Comm., 70, 1014 (1976).
ZATTA, P., ZAKIM, D., VESSEY, D.A.
The lipid intermediates arising during glycoprotein biosynthesis in liver microsomes.
Biochirn. Biophys. Acta, 441, 103 (1976).
(1977)
ALBERGONI, V., FAVERO, N., GHIRETTI, F.
The action of D-penicillamine on cytochrome oxidase in vitro.
Experientia, 33, 17 (1977).
DI STEFANO L., MEZZASALMA V., PIAZZESE S., C.RUSSO G., SALVATO B.
The subunit structure of chlorocruorin.
F.E.B.S. Letters, 79, 337 (1977).
GHIRETTI-MAGALDI, A., GHIRETTI, F., SALVATO, B.
The evolution of hemocyanin. In: Biology of Cephalopods.
(M.Nixon and J. B.Messenger Eds.) Symp. Zool. Soc. London, 38, 513, Academic Press New York, GHIRETTIMAGALDI, A., TAMINO, G.
Evolutionary studies on hemocyanins. In: Structure and Function of Hemocyanin
(Bannister, J.V., ed.) Springer Verlag, Berlin, p. 271 (1977).
GHIRETTI, F., GHIRETTI-MAGALDI, A.
The effect of vitamin C on the intracellular oxygen transport.
31
Intern. Z Vitamin und Ernahrungsf., 16, 41 (1977).
GHIRETTI-MAGALDI, A., MILANESI, C., TOGNON, G.
Hemopoiesis in Crustacea Decapoda: origin and evolution of hemocytes and cyanocytes of Carcinus maenas.
Cell Diff., 6, 167 (1977).
FERIGO E., CARDELLINI P., RODINÒ E., SALA M., SALVATO B.
Chemical changes in Xenopus laevis haemoglobin during metamorphosis.
Acta Embryologiae Experimentalis 2, 137 (1977)
JORI, G., SALVATO, B., TALLANDINI, L.
Photooxidative and spectral studies of Octopus vulgaris hemocyanin. In: Structure and Function of Hemocyanin
(Bannister, J.V., ed.) Springer
Verlag, Berlin, pp. 156-163 (1977).
SALVATO, B., RICCHELLI, F.
The minimal subunit of arthropod hemocyanin. In: Structure and Function of Hemocyanin (Bannister, J.V., ed.)
Springer
Verlag, Berlin, p. 113 (1977).
SALVATO, B., TALLANDINI, L.
Oxygen binding of associated and dissociated Octopus vulgaris hemocyanin. In: Structure and Function of
Hemocyanin
(Bannister, J.V., ed.) Springer Verlag, Berlin, p. 217-230 (1977).
SALVATO, B., ZATTA, P.
Kinetics of Reaction between hemocyanin and CN and of reconstruction of hemocyanin with K 3Cu(CN)4.
In: Structure and Function of Hemocyanin
(Bannister, J.V., ed.) Springer Verlag, Berlin, p. 245 (1977).
SALVATO, B., ZATTA, P.
The binding capacity of hemocyanins of sodium dodecylsulphate.
Comp. Biochem. Physiol., 608, 107 (1977).
(1978)
ALBERGONI, V., FAVERO, N.
Effects of Penicillamine on tissue and enzymatic metallo proteins.
Comun.Simp.Intern. sul morbo di Wilson, Buenos Aires (1978).
ALBERGONI, V., FAVERO, N., ROCCO, G.
Copper Metabolism in the Rat: Effects of Copper Loading and Copper Depletion.
Bioinorg. Chem., 0, 431 (1978).
CASSINI, A., ALBERGONI, V.
The oxidation of Sulphydryl compounds by ceruloplasmin.
Bull. Mol. Biol. Med., 3, 79 (1978).
GHIRETTI-MAGALDI, A., TAMINO, C.
L’origine della vita sulla terra.
Piccin Ed., Padova (1978).
SALVATO B., ZATTA P.
The binding capacity of hemocyanins of Sodium Dodecylsulphate.
Comp. Biochem. Physiol., 60B, 107 (1978).
(1979)
FILIPPI, B., GIUSTI, P. , CIMA, L. , BORIN,G. , RICCHELLI , F. , MARCHIORI , F.
Synthetic enkephalins. Addicting properties and conforinational studies in solution.
Int. J. Peptide Prot. Res., 14, 34-40 (1979).
GHIRETTI-MAGALDI, A., SALVATO, B., TALLANDINI, L., BELTRAMIMI, M.
The hemocyanin of Aplysia limacina : Chemical and functional characterization.
Comp. Biochem. Physio1., 62A, 579 (1979).
JORI G., PIZZI G., REDDI E., TOMIO L., SALVATO B., ZORAT P., CALZAVARA F.
Time dependence of hematoporphyrin distribution in selected tissues of normal rats and in ascites hepatoma.
Tumori, 1979, 65, 43.
RICCHELLI, F., SALVATO, B.
The binding of 1-8 ANS to the hemocyanin of Octopus vulgaris.
Eur. J. Biochem., 94, 199-205 (1979).
RUBALTELLI, F.F., JORI, C., ROSSI, E.
Modifications of serum albumin during phototherapy of jaundices newborn babies.
The Lancet, ii, 2731 (1979).
SALVATO, B., GHIRETTI-MAGALDI, A., GHIRETTI, F.
32
Hemocyanin of Octopus vulgaris. The molecular weight of the minimal functional subunit in 3M urea.
Biochemistry, 18, 2731 (1979).
VESSEY, D.A., ZATTA, P., ZACHIM, D.
Properties of dolichol-phosphate: GDP-Mannose Mannosyltransferase in liver microsomes.
Medical Biology, 57, 345 (1979).
(1980)
CARIELLO, L., SALVATO, B., JORI, G.
Partial characterization of suberitine, the neurotoxic protein purified from Suberites domuncula.
Comp. Biochem. Physiol., 67B, 337-344 (1980).
COZZANI, I., JORI, C.
Photooxidation of L-glutamate decarboxylase from Escherichia coli, sensitized by proflavine and by the
coenzyme pyridoxal phosphate.
Biochim. Biophys. Acta, 623, 84—88 (1980).
GHIRETTI, F., GHIRETTI-MAGALDI, A.
L’evoluzione a livello molecolare.
In: Basi Biol. Med. Mod., Vol. I., Ed. Medico Scientifiche, Torino (1980).
JORI, G., ROSSI, E., RUBALTELLI, F.F.
Phototherapy-induced covalent binding of bilirubin to serum albumin.
Pediat. Res., 14, 1363-1366 (1980).
RICCHELLI, F., JORI, G., SHOPOVA, N., BOTEVA, P., CENOV, N.
Fluorescence properties of native and chemically modified mesentericopeptidase.
J. Peptide Protein Res., 17, 330-337 (1980).
RICCHELLI, F., SALVATO, B., FILIPPI, B., JORI, C.
Conformational changes of Carcinus maenas hemocyanin induced by urea.
Arch. Biochem. Biophys., 202, 277-288 (1980).
SALVATO, B., BOCCU’, E., GRANDI, C., FONTANA, A., VERONESE, F.M.
Enolase from Bacillus stearothermophilus. Physicochemical characterization and Reconstitution of the active
enzyme from dissociated subunits.
J. Peptide Prot. Res., 15, 139 (1980).
SCONFIENZA, C., VAN DE VORST, A., JORI, G.
Type I and Type II mechanism in the photooxidation of L-tryptophan and tryptamine sensitized by
hematoporphyrin in the presence and in the absence of sodium dodecyl sulphate micelles.
Photochem. Photobiol., 31, 351-358 (1980).
ZATTA, P., SALVATO, B.
Reconstitution of Carcinus maenas hemocyanin in the presence of Triton Xl00.
Ciencia Biologica, 5, 111-112 (1980).
(1981)
CARIELLO, L., SALVATO, B., JORI, G.
The role of the cysteinyl and one of the tryptophyl residues in the neurotoxic action of suberitine.
Experientia, 37, 801-803 (1981).
COLAUTTI, P., MOSCHINI, C., JORI, G., CALZAVARA, F., TOMIO, L., SOTTI, G.
La terapia con radiazioni non convenzionali ionizzanti e non ionizzanti.
Quaderni Radiologia, 45, Suppl. 1, 1-56 (1981).
GHIRETTI-MAGALDI, A., SALVATO, B., TOGNON, C., MAMMI, M., ZANOTTI, C.
Structural studies on molluscan hemocyanin. In: Invertebrate oxygen-binding proteins
(Lamy J. and Lamy, J., eds.) Marcel Dekker, New York, p. 393 (1981).
GHIRETTI-MAGALDI, A.
Struttura delle emocianirie dei molluschi.
Quaderni di elicicoltura, 10, 11-22 (1981-82).
JORI, G., RICCHELLI, F., SALVATO, B., TALLANDINI, L., CANNISTRARO, S.
A study of active site topography of Octopus vulgaris hemocyanin by
photochemical techniques. In: Invertebrate Oxygen-binding proteins: Structure, Active site and
Function
(Lamy J. and Lamy, J., eds.) Marcel Dekker, New York, pp. 621—632 (1981).
REDDI, E., RICCHELLI, F., JORI, G.
Interagtion of human serum albumin with hematoporphyrin and its Zn + and Fe +_denivatives.
J. Peptide Protein Res., 18, 402-408 (1981).
RICCHELLI, F., JORI, G., SHOPOVA, M., BOTEVA, R. & GENOV, N.
Fluorescence properties of native and chemically modified mesentericopeptidase.
33
Int. J. Peptide Protein Res. 17 : 330-337 (1981).
RICCHELLI, F., FILIPPI, B., SALVATO, B.
Effects of sulphate ions on the denaturation of Carcinus maenas hemocyanin induced by urea. In: Invertebrate
Oxygen-Binding Proteins: Structure, Active Site and Function
(Lamy,J. and Lamy,J., eds.) Marcel Dekker, New York, pp. 31-39 (1981).
SALVATO, B., BELTRAMINI, N., RICCHELLI, F., TALLANDINI, L.
The reaction between Carcinus maenas hemocyanin and cyanide. In: Invertebrate Oxygen-binding proteins:
Structure, active site and function, (Lamy, J. and Lamy, J., eds.) Marcel Dekker, New York, pp. 633-643 (1981).
ZATTA, P.
Protein -lipid interactions in Carcinus maenas hernocyanin.
Comp. Biochem. Phys., 69b, 731-735 (1981).
ZATTA, P., SALVATO, B.
Reconstitution of Carcinus maenas hemocyanin in the presence of Non-ionic detergent.
J. Inorg. Biochem., 15, 269-273 (1981).
ZATTA, P., SALVATO, B.
Acetilazione degli amminoacidi-NH2 terminali nelle emocianine.
Boll. Soc. It. Biol. Sper., LVII-l9, 1927-1932 (1981).
ZATTA, P., SALVATO, B.
The polypeptide chains of Carcinus macnas hernocyanin.
In: Invertebrate Oxygen binding proteine
(Lamy,J. and Lamy,J., eds.) Marcel Dekker, New York, pp. 151-158 (1981).
(1982)
BERTOLONI, G., DALL’ACQUA, M., VAZZOLER, M., SALVATO, B., JORI, G.
Photosensitizing action of hematoporphyrin on some bacterial strains.
Med. Biol. Environ., 10, 237-242 (1982).
GENOV, N., SHOPOVA, M., BOTEVA, R., JORI, G., RICCHELLI, F.
Chemical, photochemical and spectroscopic characterization of an alkaline protease from Bacillus subtilis
variant DY. A comparison with other subtilisins.
Biochem.J., 207, 193-200 (1982).
JORI, C., REDDI, E., RUBALTELLI, F.F.
Bronze baby syndrome: evidence for increased serum porphyrin concentration.
The Lancet, i, 1072 (1982).
REDDI, E., ROSSI, E., JORI, C., SALVATO, B., TOMIO, L., PACINI, P.
Photodamage of biological systems upon irradiation with He/Ne laser in the presence of hematoporphyrin.
Med. Biol. Environ., 10, 251-258 (1982).
RICCHELLI, F.
Probing the conformation of hemocyaniris in spectroscopy.
Med. Biol. Environnement, 10, 329-331 (1982).
RICCHELLI, F., JORI, C., FILIPPI, B., BOTEVA, P., SHOPOVA, M., GENOV, N.
Effects of pH and urea on the conformational properties of subtilisin
Biochem. J., 207, 201-205 (1982).
TOMIO, L, ZORAT, P.L., CALZAVARA, F., COZZANI, I., REDDI, E., SALVATO, B., JORI, C.
Cancer phototherapy: biochemical bases and experimental results.
Med. Biol. Environ., 10, 301-307 (1982).
TOMIO, L., ZORAT, P.L., JOEl, C., REDDI, E., SALVATO, B., CALZAVARA, F.
Elimination pathway of hematoporphyrin from normal and tumor-bearing rats.
Tumori, 68, 283-286 (1982).
(1983)
BACCI, M., LINARI, R., RICCIIELLI, F., SALVATO, B.
About the origin of a novel fluorescence observed in metallo-proteins.
Inorg. Chimica Acta, 79, 276 (1983).
GENOV, N., SHOPOVA, M., BOTEVA, R., RICCHELLI, F., JORI, G.
Intramolecular distances between tryptophan residues and the active-site serine residues in alkaline bacterial
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Adaptation of a Saccaromyces cerevisiae strain to high copper concentrations.
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DELL’ANTONE P., BRAGADIN M., ZATTA P.
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Temperature-induced changes in fluorescence properties as a probe of porphyrin microenvironment in
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Porphyrins as fluorescent probes for monitoring phase transitions of lipid domains in biological
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Photodynamic therapy of experimental tumours with Zn(II)-phthalocyanine and pulsed laser
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Lasers Med. Sci. 10:43-46 (1995)
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Aluminum binds to hyperphosphorylated Tau in Alzheimer's disease: A hypothesis.
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Fisiopatologia dell'alluminio.
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La chimica dell’alluminio e i sistemi biologici. Dati certi e questioni aperte.
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BELTRAMINI, M., BORGHI, E., DI MURO, P., LA MONACA, A., SALVATO, B., SANTINI, C.
The use of SAXS in the study of quaternary organisation of giant proteins.
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Functional SAXS study of hemocyanin dioxygen-carrier protein.
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Evidences for adenine nucleotide binding in the subunits of Neurospora mitochondrial processing
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BOTEVA, R., ZLATEVA, T., DOROVSKATORAN, V., VISSER, A.J.W.G., TSANEV, R.,
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A new bioluminescent assay for studies of protein G and protein A binding to IgG
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ZATTA P., ZAMBENEDETTI P., DELL’ANTONE P.
Differential uptake of tacrine and physostigmine by murine neuroblastoma cells.
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ALZUET, G., BUBACCO, L., CASELLA, L., ROCCO, G.P., SALVATO, B., BELTRAMINI, M.
The binding of azide to copper-containing and cobalt-containing forms of hemocyanin from the
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Si(IV)-methoxyethylene-glycol-naphthalocyanine: synthesis and pharmacokinetic and photosensitizing
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the mitochondrial permeability transition pore
J. Biol. Chem., 272, n° 35 : 21938-21943 (1997).
VASSILIEV, V.B., KACHURIN, A.M., BELTRAMINI, M., ROCCO, G.P., SALVATO, B,
GAITSKHOKI, V.S. Copper depletion/repletion of human ceruloplasmin is followed by the changes in
its spectral features and functional properties.
J. Inorg. Biochem. 65, 167-174 (1997).
ZATTA P., ZAMBENEDETTI P., TOFFOLETTI A., CORVAJA C., CORAIN B.
Aluminum(III) induces alterations on the physical state of the erythrocytic membrane: an ESR
evaluation.
J. Inorg. Biochem. 65: 109-114. (1997)
ZATTA P., ZAMBENEDETTI P., GIORDANO R., FAVARATO M.
Rabbit spinal cord infactuated upon Al(III)-liposomes intravenous treatment.
J. Trace Elem. Med. Biol. 11: 170-172. (1997)
ZATTA P.
Biological models for the study of aluminum neurotoxicity.
Acta Med. Romana 35: 592-600. (1997)
(1998)
ANGELINI, E., SALVATO, B., DI MURO, P., BELTRAMINI, M.
47
Respiratory pigments of Yoldia eightsi, an antarctic bivalve.
Mar. Biol. 131, 15-23 (1998).
DAINESE, E., DI MURO, P., BELTRAMINI, M., SALVATO, B., DECKER, H.
Subunits composition and allosteric control in Carcinus aestuarii hemocyanin.
Eur. J. Biochem. 256, 350-358 (1998).
DI NOTO, V., ANGELINI, E., BELTRAMINI, M., DALLA VIA, L., SALVATO, B.
Fourier transform infrared attenuated total reflectance spectrometry of hemolymph and hemocyanin in
water solutions.
Vibrat. Spectr. 18, 1-15 (1998)
FAVILLA, R., DEL SIGNORE, F., DAINESE, E., BELTRAMINI, M., SALVATO, B.
Dissociation kinetics of hemocyanin from Octopus vulgaris.
Biochim. Biophys. Acta 1385, 115-125 (1998).
GANDOLFI L., STELLA M.P., ZAMBENEDETTI P., ZATTA P.
Aluminum alters intracellular calcium homeostasis.
Biochim. Biophys.Acta 1406: 315-320. (1998)
NORDIO M., ANDRIANI M., GEROTTO M., MARCHINI P., ZAMBENEDETTI P., ZATTA P.
Serum concentration of trace elements during different stages of chronic renal failure.Ital.
J. Min. Electrol. Metabol. 12: 81-86. (1998)
RICCHELLI, F., GOBBO, S., MORENO, G., SALET, C., BRANCALEON, L. and MAZZINI, A.
Photophysical properties of porphyrin planar aggregates in liposomes
Eur. J. Biochem. 253 : 760-765 (1998)
SALET, C., MORENO, G. RICCHELLI, F.
Effects of photodynamic action on respiration in non-phosphorylating mitochondria
Arch. Biochem. Biophys. 358 : 257-263 (1998)
SALVATO, B., SANTAMARIA, M., BELTRAMINI, M., ALZUET, G., CASELLA, L.
The enzymatic properties of Octopus vulgaris hemocyanin: the o-diphenol oxidase activity.
Biochemistry 37, 14065-14077 (1998).
ZAMBENEDETTI P., GIORDANO R., ZATTA P.
Histochemical localization of glycoconjugates on microglial cells in Alzheimer's disease brain samples
using Abrus precatorius, Maackia amurensis, Momordica charantia and Sambucus nigra lectins.
Exp. Neurol. 153: 167-171. (1998)
ZAMBENEDETTI P., GIORDANO R., ZATTA P.
Metallothioneins are highly expressed in astrocytes and microcapillaries in Alzheimer's disease brain.
J. Chem. Neuroanat. 15: 21-26. (1998)
ZATTA P., NICOSIA V., ZAMBENEDETTI P.
Evaluation of MAO activities on murine neuroblastoma cells upon acute or chronic treatment with
aluminum(III) or tacrine.
Neurochem. Intern. 32: 273-279. (1998)
ZATTA P., CERVELLIN D., ZAMBENEDETTI P.
Effects of aluminum speciation on the morphology of rabbit erythrocytes: a toxicological model.
Toxicol. in vitro 12: 287-293. (1998)
ZATTA P., ZAMBENEDETTI P., MILACIC R.
Aluminum toxicity: the relevant role of the metal speciation.
Analusis 26: M54-M58. (1998)
ZATTA P.
Interdisciplinary contacts.
J. Trace MicroprobeTechniques 16: 395-400. (1998)
ZLATEVA, T., SANTAGOSTINI, L., BUBACCO, L., CASELLA, L., SALVATO, B.,
BELTRAMINI, M.
Isolation of the met-derivative intermediate in the hydrogen peroxide dismutase activity of
deoxygenated Octopus vulgaris hemocyanin.
J. Inorg. Biochem. 72, 211-215 (1998).
(1999)
BELTRAMINI, M., DI MURO, P., FAVILLA, R., LA MONACA, A., MARIANI, P., SALVATO, B.,
SOLARI, P.L.
SAXS investigations on the temperature dependence of the conformation of 5S hemocyanin subunit of
Carcinus aestuarii.
J. Molec. Struct. 475, 73-82 (1999).
48
DAINESE, E., ANGELUCCI, C. B., VASSILIEV V., BELTRAMINI M., SALVATO B., COZZANI
I., SALVATO B., Molecular modification in ceruloplasmin from Wilson disease patients.The Italian
Journal of Biochemistry 48: 243-334 (1999).
DI NOTO V., DALLA VIA L., ZATTA P.
Conformational studies of the Trypsin-Aluminum(III) complex in solution by Raman and Fourier
transform infrared attenuated total reflectance spectroscopy.
J. Raman Spectr. 30: 209-216. (1999)
DOLASKA, P.-A., STOEVA, S., HRISTOVA, R., SCHUETZ, J., BELTRAMINI, M., SALVATO, B.,
SCHVARTZ, H., VOELTER, W.
Structural organisation of hemocyanin from lobster Homarus americanus and spectroscopic studies of
the native protein and structural subunits.
Curr. Topics Pept. Prot. Res.3 19-36 (1999)
GEBAUER, W., STOEVA, S., VOELTER, W., DAINESE, E., SALVATO, B., BELTRAMINI, M.,
MARKL, J. Hemocyanin subunit organization of the gastropod Rapana thomasiana.
Arch. Biochem. Biophys. 372, 128-134 (1999).
LANZAVECCHIA S., WADE R. H., GHIRETTI-MAGALDI A., TOGNON G., AND BELLON P.L.
A two-exposure technique for ice-embedded samples successfully reconstructs the Chlorocruorin
pigment of Sabella Spallanzanii at 2.1nm resolution.
Journal of Structural Biology 127, p. 53-63, ( 1999)
MESSORI L., ORIOLI P., BANHOLZER V., PAIS I., ZATTA P.
Formation of titanium(IV) transferrin by reaction of human serum apotransferrin with titanium
complexes.
FEBS Lett. 442: 157-161. (1999)
RICCHELLI, F., BARBATO, P., MILANI, M., GOBBO, S., SALET, C. MORENO, G.
Bis(methyloxyethyleneoxy)silicon Phthalocyanine in Tumour-Bearing Mice
J.Photochem. Photobiol. B:Biol. 50 124-128. (1999)
RICCHELLI, F., GOBBO, S., MORENO, G. and SALET, C.
Changes of the fluidity of mitochondrial membranes induced by the permeability transition
Biochemistry 38: 9295-9300 (1999)
SALVATO, B., DAINESE, E., COZZANI, I.,
The Metals: from chemistry to biology.
The Italian Journal of Biochemistry 48: 243-334 (1999).
SUWALSKY M., UNGERER B., VILLENA F., NORRIS B., CARDENAS H., ZATTA P.
Interactions of Al(acac)3 with cell membranes and model phospholipid bilayers.
J. Inorg. Biochem. 75: 263-268. (1999)
TONELLO F., DUNDON W., SATIN B., MOLINARI M., TOGNON G., GRANDI G., DEL
GIUDICE G., RAPPUOLI R. AND MONTECUCCO C.
The Helicobacter pYlori neutrophil-activating protein with dodecameric structure.
Molecular microbiology 34(2), p. 238-246 , (1999)
WÖHRLE, D., MULLER, S., SHOPOVA, M., MANTAREVA, M., SPASSOVA, G.,VIETRI, F.,
RICCHELLI, F., JORI, G.
Effect of delivery system on the pharmacokinetic and phototherapeutic properties of
bis(methyloxyethyleneoxy)silicon-phthalocyanine in tumor-bearing mice
J. Photochem. Photobiol., B:Biol. 50:124-128 (1999)
ZATTA P., TAYLOR A., ZAMBENEDETTI P., MILACIC R., DELL’ANTONE P.
Aluminum inhibits the lysosomal proton pump from rat liver.
Life Sciences 66: 2261-2266. (1999)
ZATTA P., ZAMBENEDETTI P., MILANESE M.
Activation of monoamine oxidase type-B by aluminum in rat brain homogenate.
NeuroReport 10: 1-4. (1999)
ZLATEVA T., BOTEVA R., SALVATO B., TSANEV R.,
Factors affecting the dissociation and aggregation of human interferon gamma.
International-Journal-of-Biological-Macromolecules , 26: 357-362 (1999).
(2000)
ASCONE, I., SABATUCCI, A., BUBACCO, L., DI MURO, P., SALVATO B.
Saccharose solid matrix embedded proteins:a new method for sample preparation for X-ray absorption
spectroscopy
Eur. Biophys. J. 29: 391-397 (2000).
DAINESE, E., SVERGUN, D., BELTRAMINI, M., DI MURO, P., SALVATO, B.
49
Low resolution structure of the proteolytic fragments of the Rapana venosa hemocyanin in solution.
Arch. Biochem. Biophys. 373, 154-162 (2000).
C. BEGHETTO, C. RENKEN, O. ERIKSSON, G. JORI, P. BERNARDI, F. RICCHELLI
Implications of the generation of reactive oxygen species by photoactivated calcein for mitochondrial
studies.
Eur. J. Biochem. 267:5585-5592 (2000)
HOLM, J.K., HEMMINGSEN, L., BUBACCO, L., SALVATO B., BAUER, R.,
Interaction and coordination geometries for Ag(I) in the two metal sites of hemocyanin.
Eur. J. Biochem. 267:1754-1760, (2000).
MANZANO, M., COCOLIN, L., CITTERIO, B., CONTE, B., DE BERTOLDI, M., COMI, G.,
SANTOVITO, G., BELTRAMINI, M., SALVATO, B.
Biochemical responses in a Candida famata strain adapted to high copper concentrations.
Biometals 13, 251-259 (2000).
MOLON, A., DI MURO, P., BUBACCO, L., VASILYEV, V., SALVATO, B., BELTRAMINI, M.,
CONZE, W., HELLMANN, N., DECKER, H.
Molecular heterogeneity of the hemocyanin isolated from the king crab Paralithodes camtschaticae.
Eur. J. Biochem. 267, 7046-7057 (2000).
PECERE, T., GAZZOLA, M.V., MUCIGNAT, C., PAROLIN, C., VECCHIA F.D., CAVAGGIONI
A., BASSO G., DIASPRO A., SALVATO B., CARLI M., PALU G.
Aloe-emodin is a new type of anticancer agent with selective activity against neuroectodermal tumors.
Canc. Reser. , 60: 2800-2804, (2000).
TONINELLO, A., CLARI, G., MARCON ,M., TOGNON, G. AND ZATTA ,P.
Aluminum as an inducer of the mitochondrial permeability transition.
J. of Biol. Inorg. Chem. 5,5, p. 612-623 (2000)
VALANDRO L., SALVATO B., CAIMMI R., GALZIGNA L.
Isomorphism of quasispecies and percolation models.
J. Theor. Biol. 202(3): 187-194 (2000) .
ZAKHAROVA, E.T., SHAVLOVSKI, M.M., BASS, M.G., GRIDASOVA, A.A., PULINA, M.O., DE
FILIPPIS, V., BELTRAMINI, M., DI MURO, P., SALVATO, B, FONTANA, A., VASILYEV, V.B.,
GAITSKHOKI, V.S. Interaction of lactoferrin with ceruloplasmin.
Arch. Biochem. Biophys. 374, 222-228 (2000).
ZATTA P., LAIN E., CAGNOLINI C.
Effects of Aluminum on Activity of Krebs Cycle Enzymes and Glutamate Dehydrogenase in Rat Brain
Homogenate.
Eur. J. Biochem. 267: 3049-3055. (2000)
(2001)
DOLASHKA-ANGELOVA, P., BELTRAMINI, M., DOLASKI-A., SALVATO, B., HRISTOVA, R.,
VOELTER, W.
Carbohydrate composition of Carcinus aestuarii hemocyanins.
Arch. Biochem. Biophys. 389, 153-158. (2001)
HIDALGO J., ASCHNER M., ZATTA P., VASAK M.
Roles of the metallothionein family of proteins in the central nervous system.
Brain Res. Bull. 55: 133-146. (2001)
GARBISIA S., SARTOR L., BIGGIN S., SALVATO B., BENELLI R., ALBINI A.,
Tumor Gelatinases and Invasion Inhibited by the Green Tea Flavanol Epigallocatechin-3-Gallate.
Cancer, 91: 822-832 (2001).
MOCCHEGIANI E., GIACCONI R., CIPRIANOC., MUZZIOLI M., FATTORETTI P., BERTONIFREDDARI C., ISANI G., ZAMBENEDETTI P., ZATTA P.
Zinc-bound metallothioneins as potential biological markers of ageing.
Brain Res. Bull. (2001) 55: 147-156. (2001)
MOLON, A., DI MURO, P., BUBACCO, L., VASILYEV, V., SALVATO, B., BELTRAMINI, M.,
CONZE, W., HELLMANN, N., DECKER, H.
Molecular heterogeneity of the hemocyanin isolated from the king crab Paralithodes camtschaticae.
Eur. J. Biochem. 267, 7046-7057 (2000).
MORENO, G., POUSSIN, K., RICCHELLI, F., SALET, C.
The effects of singlet oxygen produced by photodynamic action on the mitochondrial permeability
transition differ in accordance with the localisation of the sensitizer.
Arch. Biochem. Biophys. 386: 243-250 (2001)
50
NEGRISOLO E., PALLAVICINI A., BARBATO R., DEWILDE S., GHIRETTI-MAGALDI A.,
MOENS L., LANFRANCHI G.
The evolution of extracellular hemoglobins of annelids, vestimentiferans, and pogonophorans.
Journal of Biological Chemistry 276 (28) : 26391-26397 (2001)
RICCHELLI, F., CAMERIN, M., BEGHETTO, C. CRISMA, M., MORETTO, V., GOBBO, S.
SALVATO, B., SALET, C., MORENO, G.
Disaccharide modulation of the mitochondrial membrane fluidity changes induced by the membrane
potential
IUBMB Life 51: 111-116 (2001)
SALVATO, B., CUOMO, V., DI MURO, P., BELTRAMINI, M. The Effects of Environmental
Parameters on the Oxygen Consumption of Four Marine Invertebrates: a Comparative Factorial Study.
Mar Biol. 138, 659-668 (2001).
SABATUCCI, A., ASCONE, I., BUBACCO, L., BELTRAMINI, M., DI MURO P., SALVATO, B
Comparison of the X-ray absorption properties of the binuclear active site of molluscan and
arthropodan hemocyanins.
J. Biol. Inorg. Chem.(2001)
SUWALSKY M., UNGERER B., VILLENA F., NORRIS B., CARDENAS H., ZATTA P.
Effects of AlCl3 on toad skin, human erythrocytes, and model
Brain Res. Bull. 55: 205-210. (2001)
COMMUNICATIONS
(1973)
TALLANDINI L., SALVATO B., JORI C.
Foto ossidazione non sensibilizzata del sito attivo dell’emocianina. X Convegno Soc. It. Biofis. Biol.
Mol., Padova (1973).
TAMBURRO A.M., SALVATO B., ZATTA P.
Dicroismo circolare di alcune emocianine. X Convegno Naz. Soc. It. Biofis. Biol. Mcl., Padova (1973).
(1974)
JORI C., SALVATO B., TALLANDINI L.
Photochemical effects associated with the copper absorption band of native hemocyanin from Octopus
vulgaris. IV Intern. Workshop on Hemocyanin, Padova (1974).
TAMBURRO A.M., SALVATO B., JORI C.
The substitution of Cu(I) in hemocyanin with other metals. IV Workshop on Hemocyanin, Padova
(1974).
GHIRETTI F., SALVATO B., CHIRETTI-MAGALDI A.
Subunits from arthropod hemocyanins. IVmt. Workshop on Hemocyanin, Padova (1974).
CHIRETTI-MAGALDI A., MILANESI C., SALVATO B.
The synthesis of hemocyanin in Carcinus maenas. IV Int. Workshop on Hemocyanin, Padova (1974).
CHIRETTI-MAGALDI A., MILANESI C., SALVATO B.
The synthesis of hemocyanin in Carcinus maenas. IV Int. Workshop on Hemocyanin, Padova (1974).
GHIRETTI-MAGALDI A., SALVATO B, ZATTA P. The action of urea on the hemocyanin from
Octopus vulgaris. IV Int. Workshop on Hemocyanin, Padova, (1974).
GHIRETTI-MAGALDI A., MAMMI M.
Diffrazione ottica sui cristalli endocellularj di emocianina. XI Convegno Naz. Soc. It. Biofis. Biol.
Mol., Camerino (1974).
SALVATO B.
The reaction of cyanide with the hemocyanin of Octopus vulgaris. IV Intern. Workshop on
Hemocyanin, Padova (1974).
TAMBURRO A.M., SALVATO B., JORI C.
The substitution of Cu(I) in hemocyanin with other metals. IV Workshop on Hemocyanin, Padova
(1974).
(1975)
JORI G.
Convegno C.N.R. su Fotochimica, Radiochimica e Chimica delle Radiazioni, Chimica dei
Radioelementi, Chimica Nucleare (Roma, Italy). Atti del Convegno, pp. 43-58, 1975
51
(1976)
JORI G., SALVATO B., TALLANDINI L.
“Photooxidative and spectral studies of Octopus vulgaris hemocyanin”
5th International Workshop on Hemocyanin (Malta) , 1976
ZATTA P., VESSEY D.A.
Resolution of endogenous lipid intermediates of glycoproteins synthesis in liver microsomes. Fed.
Proc. 35: 948. (1976)
(1978)
ALBERGONI, V., FAVERO, N.
Uso della penicillamina nello studio (1Cl metabolismo del rame.
Cornun.Congr.Soc. It.Fisiol., Ferrara (1978).
CASSINI, A., BONAZZI, L., ALBERGONI, V.
Rilevamento del tasso ceruloplasminico nelle popolazioni di due provincie del Veneto.
Comun. Congr. Soc. It. Fisiol., Ferrara (1978).
GHIRETTI-MAGALDI, A., SALVATO, B., TOGNON, G.
Osservazioni sulla struttura quaternaria delle emocianine dei Molluschi.
Congr. Soc. It. Biochimica, Urbino (1978).
(1979)
CASSINI, A., FAZZIN, G., ALBERGONI, V.
Livelli di superossididismutasi e di rame eritrocitario e loro correlazioni nel sangue di un campione di
individui sani e di epatopatici.
Congr. Soc. It. Fisiol., L’Aquila (1979).
CASSINI, A., FAZZIN, C., ALBERGONI, V.
Tassi di ceruloplasmina e rame plasmatico e loro relazione con i livelli di rame eritrocitario e di SOD
nel sangue di un campione di individui sani ed epatopatici.
Congr. Soc. It. Fisiol., L’Aquila (1979).
REDDI E., JORI G., SALVATO B.
“Solvent effect on the hematoporphyrin-sensitized photooxidation of tryptophan”
7th Annual Meeting of the American Society for Photobiology (Monterey, USA). Book of Abstracts, p.
89, 1979
REDDI E., CANNISTRARO G., DENTI G., JORI G., SALVATO B.
“Photobleaching of carotenes by direct visible irradiation in chloroform solution”
7th Annual Meeting of the American Society for Photobiology (Monterey, USA). Book of Abstracts, p.
166, 1979
JORI G., CANNISTRARO S., RICCHELLI F., SALVATO B., TALLANDINI L.
“A study of the active site topography of hemocyanins by photochemical techniques”
EMBO Workshop on Comparative study and recent knowledge on quaternary structure and active sites
of oxygen carriers and related proteins (Tours, France).
(1980)
ROSSI E., VAN DE VORST A., JOEL G.
Hematoporphyrin-sensitized photooxidation of indoles in aqueous micellar systems. VIII International
Congress of Photobiology, Strasbourg, France (1980).
SALVATO B., BELTRAMINI M., RICCHELLI F., ZATTA P.
Aspetti cinetici della reazione tra Hc e CN-. II Convegno Nazionale di Chimica Bioinorganica, Atti dei
Congresso, Padova, pp. 59-64 (1980).
SALVATO B., ZATTA P.
The reaction between hemocyanin and CN.
Atti FEBS, Jerusalem (1980).
SALVATO B., JORI G., CANNISTRARO S.
Specific photooxidation of hemocyanin active site promoted by photoexcitation of the peotein legandcopper charge transfer systems. International Conference on oxygen and oxy—radicals in Chemistry
and Biology, Austin (Texas), Book of abstracts, pp. 57-58 (1980).
JORI C., SALVATO B., CANNISTRARO S.
Fotoossidazìone dei sito attivo dell’Hc per fotoeccitazione della banda a trasferimento di carica legando
proteina-rame. II Convegno di Chimica Bioinorganica, Padova (1980).
52
REDDI E., RICCHELI F., JORI G.
“Interaction of human serum albumin with hematoporphyrin and its Zn 2+- and Fe3+-derivates”
8th International Congress on Photobiology (Strasbourg, France). Book of Abstracts, abstract P-220,
1980
JORI C., SPIKES J.D., STRAIGHT R.C.
Photosensitized oxidations within complex biological structures.
International Conference on Oxygen and Oxy-radicals in Chemistry and
Biology, Austin, Texas (1980).
TALLANDINI L., ROSSI F.
Emocianina di Carcinus maenas. Caratteristiche fisiologiche e modulazioni allosteriche da parte di
effettori naturali.
XVII Congr. Naz. Soc. It. Biofis. Biol. Noi., Atti dei Convegno, p. 12 (1980).
CASSINI A., TALLANDINI L., ALBERGONI V.
La superossidodismutasi negli Invertebrati: Molluschi.
Congr. Soc. It. Fisiol., Caserta (1980).
TALLANDINI L., CASSINI A., ALBERGONI V.
Le superossidodismutasi negli Invertebrati. Anellidi. XXXII Congr. Naz. Soc. It. Fis., Atti dei
Congresso, Caserta,p.232 (1980).
ZATTA P., SALVATO B.
Ricostituzione dell’emocianina di Carcinus maenas. II Convegno Naz. di Chimica Bioinorganica,. Atti
dei Convegno, Padova, pp. 65—67 (1980).
(1981)
ZATTA P.
Zn-protein interactions in Carcinus maenas hemocyanin.
Acta A.A.A.S., Washington, Abstract (1981).
RICCHELLI F., JOEl C., GENOV N., SHOPOVA N.
Comparative studies on the conformation of some pro teases. In: Proc. 1 st mt. Conf. Chem. Biotechn. of
products, Varna (Bulgaria), September 21-26, (1981).
JORI G., REDDI E., SALVATO B.
“Evidence for increased photosensitizing efficiency of protein-bound dyes”
9th Annual Meeting of the American Society for Photobiology (Williamsburg, USA). Book of
Abstracts, p. 187, 1981
JORI G., REDDI E., ROSSI B., SALVATO B.
“Effetto della struttura chimica e dell’ambiente di reazione sul meccanismo e sull’efficienza
dell’attività fotosensibilizzatrice di porfirine”
V Riunione Società Italiana di Biofisica Pura e Applicata (Perugia, Italy). Book of Abstracts, pp. 4345, 1981
RICCHELLI F., SALVATO B., JORI G.
“Studi conformazionali sull’emocianina di Octopus vulgaris negli stati di aggregazione”
V Riunione Società Italiana di Biofisica Pura e Applicata (Perugia, Italy). Book of Abstracts, pp. 8485, 1981
(1982)
SALVATO B., JORI G.
“Mono-and di-phenol oxidase activity of Octopus vulgaris hemocyanin”
EMBO Workshop on Structure and Function of Invertebrate Respiratory Proteins (Leeds, United
Kingdom). Book of Abstracts, p. 12, 1982
RICCHELLI F., ROSSI E., SALVATO B., JORI G., BANNISTER J.V.
“Fluorescence studies on copper/zinc superoxide dismutase from bovine erythrocytes”
3rd International Conference on Superoxide and Superoxide Dismutase (New York, USA). Book of
Abstracts, pp. 320-323, 1982
TALLANDINI L., CASSINI A., RICCHELLI F. FILIPPI B.
Chemical and spectroscopic characterization of a copper/zinc superoxide dismutase from a marine
bivalve mollusc ( Mytilus galloprovincialis ). ibidem , Abs. PI 11.
(1983)
BERTOLONI G., DALL’ACQUA M., VAZZOLER M., SALVATO B., JORI G.
“Bacterial and yeast cells as models for studying the photosensitization by hematoporphyrin”
International Symposium on Porphyrins in Tumor Phototherapy (Milano, Italy). Book of Abstracts, pp.
53
37-39, 1983
RICCHELLI F., JORI G., SHOPOVA M., BOTEVA R., GENOV N.
“Lanthanide spectral properties as a probe of calcium-binding sites in mesentericopeptidase”
1st International Conference on Bioinorganic Chemistry (Firenze, Italy) , 1983
BACCI M., LINARI R., RICCHELLI F., SALVATO B.
About the origin of a novel fluorescence observed in metalloproteins. ibidem , p. 276.
ZATTA P., RICCHELLI, F.
Metal-protein interaction in Carcinus maenas hemocyanin. ibidem , pp. 155-156.
ZATTA P., ZAKIM D.
UDP-Glucuronyl-transferase activity in Cancer magister.
Abstract FEBS Meeting, Bruxelles (1983).
ZATTA P.
Contributo deli ‘emocianirta all ‘equilibrio osmotico di Carcinus maenas. Atti Convegno SIBS-SIF—
SINU, St. Vincent (1983).
(1984)
ZATTA P.
Interazione Ca2+_Taurina nel cuore di Carcinus maenas. Atti Convegno SIBS-SIF-SINU, 65 (1984).
ZATTA P.
Sulla partecipazione dell'emocianina all'osmoregolazione del Carcinus maenas. Conv. Unione
Zoologica Italiana. Padova, Italy, June 26-30. Boll. Zool. 51: suppl. 117. (1984)
ZATTA P., BISMONDO A.
Interaction between Taurine and metal ions. FEBS-Meet., Moscow, Russia, XXII-148. (1984)
BERTOLONI G., SALVATO B., JORI G.
“Photosensitization of microbes by hematoporphyrin” Congresso Annuale della Società Italiana di
Fotobiologia (Pavia, Italy). Book of Abstracts, p. 435, 1984
BERTOLONI G.
“Studies on the mechanism of cell photosensitization by hematoporphyrin”
9th International Congress on Photobiology (Philadelphia, USA). Photochem. Photobiol. 39:45S, 1984
JORI G., REDDI E., SALVATO B., TOMIO L., COZZANI I.
“Liposomes and lipoproteins as efficient carriers of porphyrins to tumor cells in vitro and in vivo”
Workshop on Porphyrin Photosensitization (Philadelphia, USA). Book of Abstracts, abstract 27, 1984
RICCHELLI F., GOYAL G.C., GROSSWEINER L.I.
Structure and photophysics of HpD-A.
Ninth International Congress on Photobiology and 12th Annual Meeting of the American Society for
Photobiology Philadelphia , Pennsylvania , U.S.A. , 1-6 July 1984 , Abs TAM-F 2.
(1985)
RICCHELLI F., JORI G.
“Spectroscopic studies on the intraliposomal distribution of porphyrins”
International Meeting on Porphyrins as Phototherapeutic Agents for Tumor and Other Diseases
(Alghero, Italy). Book of Abstracts, p. 35, 1985
RICCHELLI F., FILIPPI B., GOBBO S., SIMONI E., TALLANDINI L., ZATTA P.
Functional and Structural Properties of the 50,000 D Subunit of Octopus vulgaris hemocyanin. Int.
Symp. on: Invertebrate Oxygen Carriers. Tutzing-Bavaria, Fed. Rep. Germany, July 29 - August 1, p.
41. (1985)
BELTRAMINI M., RICCHELLI F., JORI G., ZIRON L., PAGNAN A.
“Interaction of hematoporphyrin with isolated lipoproteins: a spectroscopic study”
International Meeting on Porphyrins as Phototherapeutic Agents for Tumor and Other Diseases
(Alghero, Italy). Book of Abstracts, p. 37, 1985
BOMBI G.G., CORAIN B., SESTI A.G., ZATTA P.
Chemical and Biological Investigations on Aluminum Neurotoxicity. New Trends in Aging Research,
Bologna, Italy, November 6-9(CNR-NIH-EURAGE), p. 114. (1985)
REDDI E., BELTRAMINI M., RICCHELLI F., JORI G.
“Spectroscopic studies on the interaction of hematoporphyrin with liposomes and lipoproteins”
13th Annual Meeting of the American Society for Photobiology (New Orleans, USA). Book of
Abstracts, p. 45, 1985
REDDI E., RICCHELLI F., BELTRAMINI M., JORI G.
“Interaction of porphyrins with liposomes and lipoproteins”
Reunion sur la Photosensibilisation, Socièté Francaise de Photobiologie (Orsay, France). Book of
54
Abstracts, abstract D-7. (1985)
TALLANDINI L., SIMONI E., ZATTA P.
Interazione lipidi-proteina nell’emocianina di Carciuns maenas.
31 Congr. Naz. SIB, Cleub Ed., Bologna, H 13 (1985).
(1986)
GENOVA L., GENOV N., BOTEVA R., PRODANOV M., RICCHELLI F., SALVATO B.
Superoxide dismutase from Prunus cerasifera.
International Symposium and Colloquium School on Activated Oxygen Species in Biological Systems
, Varna , Bulgaria , 29 September - 5 October , 1986 , Abs. A 25.
GENOVA L., RATKOV A., PEIKOVA S., ANGELOVA M., GENOV N., BOTEVA R.,
RICCHELLI F. SALVATO B.
Purification and characterization of superoxide dismutase from bacterial cell mass of amino acid
producers. ibidem, Abs. A 26.
SALVATO B., BELTRAMINI M., ALVIGGI M., GIACOMETTI G.M.
On the non equivalence of copper ions in the active site of hemocyanin. In: Atti del Congresso
Nazionale di Cibernetica e , Lipari 1985 (Chilleni, S. e Frediani, C., eds.) Istituto di Biofisica del CNR,
Pisa, pp. 1-6 (1986).
BOMBI G., CORAIN B., GIORDANO R., PAGANI D., SESTI A.G., ZATTA P.
Chemical and biological investigations on Aluminum neurotoxicity.
In: Neuroendocrine system and aging (Vezzadini, Facchini, Labo eds.), Eurage, pp. 253-258 (1986).
RICCHELLI F., JORI G.
“Fluorescence studies on liposome-bound hematoporphyrin”
1st Congress of the European Society for Photobiology (Grenoble, France). Book of Abstracts, abstract
P51, 1986
ZATTA P., DI STEFANO A.
Analisi ultrastrutturale delle branchie di quattro specie di crostacei decapodi: Carcinus maenas, Cancer
pagurus, Homarus americanus, Austropotamobius pallipes italicus. Conv. Naz. Soc. Ital. Biol. Marina.
Cesenatico, Italy , September 9-12. (1986)
MILANESI C., ZATTA P.
Aspetti ultrastrutturali delle branchie di due specie di crostacei. Conv. Naz. Unione
Zoologica Italiana. Roma, Italy, October 6-11, Boll. Zool. 53: suppl., 23. (1986)
ZATTA P., CORAIN B., BOMBI G.G., GIORDANO R., STELLA M.P.
Toxicity of lipophilic form of aluminum(III). Ann. Meet. Soc. Ecotoxicol. and Environm. Safety, ISISRoma, Italy, November 12-14, p.15. (1986)
ZATTA P., FAVARATO M., DI STEFANO A.
L'attivita' L- -amminotransferasica nell'ipostress osmotico di Carcinus maenas. Conv. Naz.Soc. Ital.
Biochim. Messina, Italy, September 28 - October 1, BT-5 (1986)
ZATTA P., FAVARATO M., DI STEFANO A.
L'attivita' transaminasica nei crostacei in funzione della salinita'. XVIII Conv. Naz. Soc. Ital. Biol.
Marina, Cesenatico, Italy, September 9-12, BM-17. (1986)
(1987)
PELLERITO L., STOCCO G.C., GIANGUZZA A., DIA G., GIRASOLO M.A, CEFALU R.,
MANSUETO C., SALVATO B., BELTRAMINI M., TALLANDINI L., RICCHELLI F.
Bioinorganic investigations on metallic and organometallic moieties .
Incontro su : Chimica dei Sistemi e dei Processi Biologici , Modena , 19-20 Gennaio 1987
Abs. p.1.
RICCHELLI F., JORI G.
“Porphyrin aggregation in liposomes”
4th International Conference in Chemistry and Biotechnology of Biologically Active Natural Products
(Budapest, Hungary), 1987
RICCHELLI F., TOGNON G., JORI G.
“Influence of the liposome organization on the fluorescence properties of hematoporphyrin”
2nd Congress of the European Society for Photobiology (Padova, Italy). Book of Abstracts, abstract
C181, 1987
RICCHELLI F., TOGNON G., JORI G.
“Aggregation processes of hematoporphyrin and hematoporphyrin dimethylester in liposomes”
Conference on New Directions in Photodynamic Therapy (Cambridge, Massachusetts, USA), 1987
RICCHELLI F., BELTRAMINI M., SALVATO B.
55
A preliminary conformational study of the copper sites of laccase .
Third International Conference on Bioinorganic Chemistry , Noordwijkerhout ,The Netherlands, 6-10
July,1987, Abs. R-20-K.
ZATTA P.
Catecholamine and serotonin in the hyposmotic stress of Carcinus maenas. Int. Symposium on
Transport in Cell and Epithelia. Copenhagen, Denmark, August 16-21. P. C15. (1987)
ZATTA P., CORAIN B., GIORDANO R., FAVARATO M., BOMBI G.G.
Coordination State and Toxicity of Aluminum. III Int. Conf. on Bioinorg. Chem. Noordwijkerhout,The
Netherlands, July 6-10, R-39-0, p.26. (1987)
SPEZIALI M., RIZZIO E., ORVINI E., PERAZZOLO M., ZATTA P.
Gallium Determination in Different Human Brain Sites. Int. Symp. on Environmental Aspects of Trace
Elements. UNESCO Headquarter. Paris , France, December 1-4, p.77. (1987)
TALLANDINI L., SALVATO B., BELTRAMINI M., PIAZZESI A., RICCHELLI F.
Co(II)-substitution studies on bovine erythrocyte superoxide dismutase. Ibidem , Abs. R-23-K.
TALLANDINI L., SALVATO B., BELTRAMINI M., PIAZZESI A. & RICCHELLI F.
Active site properties of bovine erythrocyte superoxide dismutase. ibidem , Abs. B-3. (1988)
MILANESI C., ZHOU C., RICCHELLI F. JORI G.
Ultrastructural studies on the mechanism of photodynamic therapy.
10th International Congress of Photobiology , Jerusalem , Israel , 30 October - 5 November 1988 ,
Abs. p. 11.
CORAIN B., BOMBI G.G., ZATTA P.
Aluminum Coordination Compounds in Biological Investigations: Novel Physiopathological
Perspectives?. III Hans Wolfgang Nurnberg Memorial Workshop on Toxic Metal Compounds
(Interrelation between Chemistry and Biology). Follonica, Italy, April 10-14. (1988)
CORAIN B., BOMBI G.G., ZATTA P., PERAZZOLO M.
Aluminum Speciation and Biological Effects. I Int. Meet. on Molecular Mechanisms of Metal Toxicity
and Cancerogenicity.Urbino,Italy, September 19-22, p.85. (1988)
ZATTA P., CORAIN B., BOMBI G.G., PERAZZOLO M.
The Role of the Speciation in the Effects of Aluminum(III) on Membranes Stability and on Selected
Enzymatic Activities. I Int. Conf. on Alzheimer's Disease and Related Disorders. Las Vegas, NV, USA,
September 6-9, p.319. (1988)
BOTEVA R., SEVEROV S., GENOV N., BELTRAMINI M., FILIPPI B., RICCHELLI F.,
TALLANDINI L., TOGNON G., SALVATO B.
General characterization of a mollusc gastropod ( Rapana thomasiana ) hemocyanin.
Symposium on Invertebrate Dioxygen Carriers , Leuven , Belgium , 23-27 July 1989 , Abs.p.6.
(1989)
RICCHELLI F., JORI G., MORENO G., VINZENS F., SALET C.
Photosensitization of mitochondria by liposome-incorporated protoporphyrin .
Third Congress of the European Society of Photobiology , Budapest, Hungary, 27 August - 2
September 1989 Abs. P-93.
RICCHELLI F.
Photosensitization of subcellular organelles by porphyrins and phthalocyanines .
International Conference of Photodynamic Therapy , Sofia, Bulgaria , 3-5 October 1989 , Abs. L. 22 p.
16.
ZATTA P., PERAZZOLO M., FAVARATO M., BOMBI G.G., NICOLINI M.
Role of the Metal Speciation in the Action of Aluminum(III) Complexes on Plasmatic Membranes.
FEBS-Meet. Rome, Italy, July 2-7. (1989)
ZATTA P., PERAZZOLO M., FAVARATO M., BOMBI G.G., NICOLINI M.
The Effect of Aluminum Speciation on the Rabbit Erythrocytes. IV Int. Conf. on Bioinorganic
Chemistry. Cambridge, MA, USA, July 23- 28. J. Inorg. Biochem. 36(3-4), N014. (1989)
CORAIN B., BOMBI G.G., NICOLINI M., ZATTA P.
Novel Chemical and Biological Models of Aluminum Toxicity Based on Hydrolytically Stable and
Diversely Hydrophilic Aluminum Compounds. First Int. Conf. on Aluminum and Health. Orlando,
Florida, December 10-13. (1989)
BOMBI G.G., CORAIN B., NICOLINI M., ZATTA P.
Sviluppo di nuovi modelli chimici e biologici per lo studio della tossicita' dell'alluminio. Congr. Istituto
Superiore Sanita', Roma, Italy, September 21, p. 71. (1989)
(1990)
56
RICCHELLI F., JORI G., MORENO G., VINZENS F., SALET C.
Effect of the carrier on the photosensitizing properties of porphyrins in mitochondria.
IX Congresso della Società Italiana di Biofisica Pura e Applicata , Marciana Marina, 12-18 Maggio
1990, Abs. p. 153.
CORAIN B., PERAZZOLO M., FONTANA L., BOMBI G.G., TAPPARO A., CORVAJA C.,
FAVARATO M., ZATTA P.,
The Effects of Aluminum(III) on the Integrity of Plasmatic Membranes: Relevance to Alzheimer's
Disease. II Int. onf. on Alzheimer's Disease and Related Disorders. Toronto, Canada, July 15-20.
Neurobiol. of Aging 11(3), 256. (1990)
FAVARATO M., PERAZZOLO M., GOBBO S., NICOLINI M., ZATTA P.
Effect of Aluminum(III) Speciation on the Permeability of the Blood-BrainBarrier: Possible
Implications in Aluminum Intoxication, Dialisys and Dementia. II Int. Conf. on Alzheimer's Disease
and Related Disorders. Toronto, Canada, July 15-20. Neurobiol.of Aging, 11(3), 259. (1990)
FAVARATO M., MIZZEN C., KRUCK T.P.A., KRISHNAN B., ZATTA P., McLACHLAN D.T.
Chromatographic Resolution of Aluminum Binding Components in Human Serum. II Int. Conf. on
Alzheimer's Disease and Related Disorder. Toronto, Canada, July 15-20. Neurobiol. of Aging.11(3),
260. (1990)
STULTS N.L., ZATTA P., STOCKS N., CORMIER., M.J. CUMMINGS R.D.
The Use of the Recombinant Bioluminescent Protein Aequorin for Solid Phase Assays in Microtiter
Plates. ASB, Mol. Biol.and The Am. Assoc. Immunol., Joint Meet, New Orleans, June 4-7, 2675.
(1990)
ZATTA P., FAVARATO M., PERAZZOLO M., FONTANA L., NICOLINI M.
Lipophilic Aluminum (III) Complexes Modify the Permeability of the Blood-Brain Barrier. 35o Congr.
Soc. Ital. Biochimica, Bari, Italy, September 29 - October 3. Italian Biochemical Soc. Trans. 2(3),
382. (1990)
PERAZZOLO M., FONTANA L., FAVARATO M., CORAIN B., BOMBI G.G. TAPPARO A.,
NICOLINI M., CORVAJA C., ZATTA P.
Effects of Aluminum (III) Speciation on Plasmatic membranes. I Int. Symposium on Metal Ions in
Biology and Medicine. Reims, France, May 16-19.Trace Elem. in Medicine.7, 62. (1990)
ZATTA P., CUMMINGS R.D., SMITH D.F., CORMIER M.J.
Applications of recombinant bioluminescent proteins in assays of potential tumor markers. VI Int.
Symp. on Bioluminescence and Chemioluminescence. Cambridge ,U.K., September 10-13. (1990)
(1991)
TRONCHIN M., GOBBO S., RICCHELLI F., JORI G., MORENO G., VINZENS F., SALET C.
“Fotoinattivazione di mitocondri sensibilizzata da porfirine”
IX Congresso Annuale della Società Italiana di Fotobiologia (Capri, Italy). Book of Abstracts, 1991
RICCHELLI F., JORI G., GOBBO S., MORENO G., VINZENS F., SALET, C.
“Comparison between the photosensitizing efficiency of liposome-bound hematoporphyrin and
protoporphyrin on isolated mitochondria”
4th Congress of the European Society for Photobiology (Amsterdam, The Netherlands). Book of
Abstracts, abstract A-55, p. 77, 1991
RICCHELLI F., JORI G., MORENO G., SALET C.
“Mitochondria as models of complex functional systems to study photosensitization by liposomebound porphyrins”
International Conference on Photodynamic Therapy and Laser Medicine (Beijing, China). Book of
Abstracts, abstract L78, p. 80, 1991
RICCHELLI F., BOTEVA R., SARTOR G.,DECKER H.
Proprietà di fluorescenza dell 'emocianina di tarantola ( Eurypelma californicum ).
Convegno Annuale della Società Italiana di Fotobiologia , Capri , 10-11 Giugno 1991 .
ZATTA P., FACCI L., LEON A., CORAIN B., PERAZZOLO M., FAVARATO M.
Role of Metal Speciation in the Effect of Aluminum(III) on Murine Neuroblastoma Cells. IV Hans
Wolfgang Nurnberg Memorial Workshop on Toxic Metal Compounds (Interrelation between Chemistry
and Biology). Les Diablerets, Switzerland, March 4-8, 67. (1991)
FAVARATO M., ZATTA P., NICOLINI M.
Serine Proteases: Inhibitory Effect of Aluminum(III): Potential Implications on Alzheimer's Disease. II
Int. Springfield Symposium on Advances in Alzheimer Therapy. Springfield, Illinois, May 3-5, P16.
(1991)
RICCHELLI F., BOTEVA F., SARTOR G., DECKER H.
57
Sonde fluorescenti per lo studio delle variazioni conformazionali del sito attivo
tarantola (Eurypelma californicum ). ibidem.
dell'emocianina di
(1992)
BOTEVA R., RICCHELLI F., SARTOR G., DECKER H.
Fluorescence probes to study conformational changes of hemocyanin from tarantula (Eurypelma
californicum) during oxygenation.
International Congress on Invertebrate Dioxygen Carriers, Lunteren, The Netherlands, 12-17 April
1992, Abs. V-P07.
RICCHELLI F., JORI G., MORENO G., SALET C.
“Porphyrin – photosensitization of mitocondria”
International Conference on Photodynamic Therapy and Medical Laser Applications (Milano, Italy).
Lasers Med. Sci., 7:252, 1992
RICCHELLI F., DABBENI-SALA F., JORI G., MORENO G., SALET C.
“Photosensitization of mitochondria by liposome-bound porphyrins”
11th International Congress on Photobiology (Kyoto, Japan). Book of Abstracts, abstract 147, p. 305,
1992
ZATTA P., TOLLARDO A.M., FAVARATO M., BAZZATO G., MORACCHIELLO P., NICOLINI
M.
Rheological measurements of whole blood from Alzheimer's disease, dialysis and multinfarctual
dementia patients. The Third International Conference on Alzheimer's disease and Related Disorders.
Abano, Italy, July 12-17 . Neurobiol. Aging 13 (suppl. 1), 110. (1992)
FAVARATO M., ZANONI S., ZATTA P.
Unambigous aluminum(III) localization in senile plaque core from Alzheimer's disease. The Third
International Conference on Alzheimer's disease and Related Disorders. Abano, Italy, July 12-17.
Neurobiol. Aging 13 (suppl. 1), 160. (1992)
CORAIN B., NICOLINI M., ZATTA P.
Relevance of metal speciation in directing the biological effects of aluminum(III). The Third
International Conference on Alzheimer's disease and Related Disorders. Abano, Italy, July 12-17.
Neurobiol. Aging 13 (suppl. 1), 372. (1992)
ZATTA P.
Controversial aspects on aluminum(III) accumulation and compartmentation in Alzheimer's disease.
The Third International Conference on Alzheimer's disease and Related Disorders. Abano, Italy, July
12-17. Neurobiol. Aging 13 (suppl. 1), 373. (1992)
MATTIELLO G., GEROTTO M., FAVARATO M., LAZZARI F., ZANOBONI V., PILONI M.G.
ZATTA P.
Microelemental analysis of plasma from Alzheimer's disease and multinfarctual dementia patients. The
Third International Conference on Alzheimer's disease and Related Disorders. Abano, Italy, July 12-17.
Neurobiol. Aging 13 (suppl. 1), 385. (1992)
TISATO F., ZAMBENEDETTI P., CORAIN B., ZATTA P.
Modelling the interaction of membrane phospholipid components with Al(III) in water and aprotic
solvents: A NMR approach.The Third International onference on Alzheimer's disease and Related
Disorders. Abano, Italy, July 12-17. Neurobiol. Aging 13 (suppl. 1), 388. (1992)
FAVARATO M., ZANONI S., ZANOTTI A., ZATTA P.
Aluminum(III) induces neuronal degeneration in rat brain. The Third International Conference on
Alzheimer's disease and Related Disorders. Abano, Italy, July 12-17. Neurobiol. Aging 13 (suppl. 1),
402. (1992)
MASIERO S., ZATTA P.
Neuritogenic effects of aluminum(III) on murine neuroblastoma cell cultures.The Third International
Conference on Alzheimer's disease and Related Disorders. Abano, Italy, July 12-17. Neurobiol. Aging
13 (suppl. 1), 438. (1992)
ZANONI S., BORDIN C., FAVARATO M., GIORDANO R., ZATTA P.
Glycosylation study of cerebral cortex from Alzheimer's disease patients with lectins. The Third
International Conference on Alzheimer's disease and Related Disorders.Abano, Italy, July 12-17.
Neurobiol. Aging 13 (suppl. 1), 547. (1992)
MIRZABEKOV T., BALLARIN C., SORGATO M.C. NICOLINI M., ZATTA P.
Effect of different aluminum compounds on the outer mitochondrial membrane channel, VDAC. The
Third International Conference on Alzheimer's disease and Related Disorders. Abano, Italy, July 12-17.
Neurobiol. Aging 13 (suppl. 1), 550. (1992)
58
ARSLAN P., BELTRAME M., NICOLINI M., MASIERO S., ZATTA P. Hyaluronic acid reacts with
neurofilament proteins in clonal lines of neuroblastoma. Societa' Italiana di Biochimica. Perugia, Italy,
September 21-24, F15. (1992)
ZATTA P., CANTINI M., MASIERO S., ARSLAN P.
Murine neuroblastoma cells: neuritogenic effects produced by Al(III) are related to the metal
speciation.5th Congr. Soc. Ital. Neuroscienze.Modena,Italy, December, 1-4. Neurosc. Lett. Suppl. 43.
(1992)
ZATTA P., ZANONI S., FAVARATO M.
The identification of aluminum in the core of mature plaques from Alzheimer's disease.5 th Congr. Soc.
Ital. Neuroscienze. Modena, Italy, December 1-4. Neurosc. Lett. Suppl. 43. (1992)
(1993)
RICCHELLI F., GOBBO S., JORI G., MORENO G., SALET C.
“Fotoinattivazione di mitocondri sensibilizzata da ftalocianine” XI Congresso Annuale della Società
Italiana di Fotobiologia (Salice Terme, Italy). Book of Abstracts, abstract 13M, 1993
RICCHELLI F., GOBBO S., JORI G., MORENO G., SALET C.
“Phthalocyanine-sensitized photoinactivation of mitochondria”
5th Congress of the European Society for Photobiology (Marburg, Germany). Book of Abstracts,
abstract P 4, p. 180, 1993
ZATTA P., MORACCHIELLO P., BAZZATO G.
Dismorfismo eritrocitario e alluminemia in soggetti uremici. 34 o Congresso Naz. Soc. Naz. Nefrologia,
Pisa, Italy, May 18-21.Giornale Italiano di Nefrologia 10, p.81, 282. (1993)
ZATTA P., BAZZATO G., MORACCHIELLO P., NICOLINI M., TOLLARDO A.M.
Misure reologiche in soggetti uremici sottoposti ad emodialisi extracorporea e CAPD. 34 o Congresso
Naz. Soc. Ital. Nefrologia, Pisa, Italy, May 18-21.Giornale Italiano di Nefrologia 10, p. 82, 283. (1993)
FAVARATO M., ZANONI S., NICOLINI M., ZATTA P.
Positive reaction for A4 protein in the rat brain treated with aluminum maltolate.Fondation Ipsen pour
la reserche therapeutique. Colloques medecine et recherche: Amyloid protein precursors in
development, aging and Alzheimer's disease. Fondation Ipsen Colloques medecine et recherche. Lyon,
France, June 21, p.42.. (1993)
(1994)
RICCHELLI F. , GOBBO S., JORI G. NIKOLOV P.
“Studi spettroscopici sull’interazione di ftalocianine con membrane mitocondriali”
Convegno Nazionale Congiunto di Fotobiologia e Fotochimica (Volterra, Italy). Book of Abstracts,
abstract 7S, 1994
RICCHELLI F. GOBBO S, TOGNON G. , JORI G.
Spectroscopic studies on the interaction of phthalocyanines and porphyrins with lipid membranes:
determination of the nature of dye - binding sites in mitochondrial membranes.
XII Congresso SIBPA , Palermo 23 - 28 Settembre 1994 . Abs. D-P10.
DELL’ANTONE P., BRAGADIN M., ZATTA P.
The accumulation of tacrine in acidic compartments of the cell. Intern. Conf: Dementia in Parkinson's
Disease. Jerusalem, Israel, March 20-24. Behavioural Neurology 7:11. (1994)
ZATTA P., ZAMBENEDETTI P., CORAIN B.
Rilevanza della speciazione del metallo sull'interazione tra alluminio(III) e sistemi biologici. V Nation.
Conf.:Interazione di metalli e composti con biomolecole. S. Agnello di Sorrento, Italy, April 7-9, p. 45.
(1994)
BRAGADIN M., DELL’ANTONE P., PALUMBO M., ZATTA P.
Tacrine accumulates in the acidic cell compartments: potential therapeutics implication. IV Int. Conf.
on Alzheimer's Disease and Related Disorders. Minneapolis, MN, USA, July 29- August 3.
Neurobiology and aging 15 S1: P421. (1994)
BRAGADIN M., DELL’ANTONE P., PALUMBO M., ZATTA P.
Effects of anticholinergic drugs on neuroblastoma cells and isolated lysosomes. XVI Int. Congr. of
Biochemistry and Molecular Biology. New Delhi, India, September 19-22, P10-38. (1994)
DELL’ANTONE P., BRAGADIN M., ZATTA P.
The accumulation of Tacrine, Amantadine and Trihexyphenidyl in acidic compartments of the cell. XII
International Congress of Pharmacology, Montreal, Canada, July 23-29, 13.9. (1994)
ZATTA P., BRAGADIN M., ZAMBENEDETTI P., DELL’ANTONE P.
Activation of acetylcholinesterase by aluminum. Int.Conf.: Molecular mechanisms of enzyme action.
Bangalore, India, September 23-25 , P20. (1994)
59
ZATTA P., ZAMBENEDETTI P.
The relevance of the metal speciation on the interaction between aluminum and biological systems.III
Congr. Naz. A.I.S.E.T.O.V. Modena, Italy, October 28-29 , p. 47 (1994)
(1995)
RICCHELLI F., GOBBO S, TOGNON G., JORI G., MORENO G., SALET C.
“Temperature-induced changes in fluorescence properties as a probe of porphyrin microenvironment in
mitochondrial membranes” Congresso Annuale della Società Italiana di Fotobiologia (Bressanone,
Italy). Book of Abstracts, p. 19, 1995
RICCHELLI F., GOBBO S., JORI G., SALET C. MORENO G.
“The partition of hematoporphyrin in mitochondrial membranes: formation of noncovalent linear
dimers” 6th Congress of the European Society for Photobiology (Cambridge, United Kingdom). Book
of Abstracts, p. 85, 1995
SHOPOVA M., PEEVA M., MANTAREVA V., MICHAILOV N., STOICHNKOVA N., JORI G.,
RICCELLI F., WHORLE D., MULLER S.
“The significance of sensitizer photophysical properties for the phototherapeutic effect at pigmented
melanoma” 6th Congress of the European Society for Photobiology (Cambridge, United Kingdom).
Book of Abstracts, p. 91, 1995
ZATTA P., ZAMBENEDETTI P.
Attivazione dell'acetilcolinesterasi da parte dell'alluminio. Riun. Soc. Ital. Neuroscienze. Modelli
sperimetali in neurologia e psichiatria. Bosisio Parini, Italy, October 15, C7. (1995)
(1996)
MANTAREVA V., SHOPOVA M., SPASSOVA G., WOHRLE D., MULLER S., JORI G.,
RICCHELLI F.
Pharmacokinetic and photosensitizing properties dependence on the tumor model of cremophor
delivered Si(IV) -methoxyethyleneglycol-naphthalocyanine .
12th International Congress on Photobiology , Vienna , Austria , 1-6 -1996, Abs.
RICCHELLI F., MILANI M., GOBBO S., TOGNON G., JORI G., MORENO G., SALET C.
“Effetti della fotosensibilizzazione con porfirine sul trasporto del Ca 2+ in organelli subcellulari”
II Convegno Nazionale Congiunto di Fotobiologia e Fotochimica (Maratea, Italy). Book of Abstracts,
abstract S8, p. 42, 1996
AIMO E., DELL’ANDREA E., GAMBILLARA G., MARTINI G., ZAMBENEDETTI P., ZATTA P.
I Int. Congr. on mineral waters and soft drinks. Florence, Italy, May 15-17, p. 63. (1996)
ZATTA P., ZAMBENEDETTI P.
Aluminum speciation and biological effects: implications in human and experimental toxicology.
NATO-ASI. Cytotoxic, Mutagenic and Carcinogenic Potential of Heavy Metals Related to Human
Environment. Przesieka, Poland, June 15-26, p. 107-108. (1996)
ZATTA P., ZAMBENEDETTI P.
Al(III) speciation and cell pathology. NATO-AASI. Cytotoxic, Mutagenic and Carcinogenic Potential
of Heavy Metals related to Human Environment. Przesieka, Poland,June 15-26, p. 228-229. (1996)
ZATTA P.
Aspetti storici ed attuali sull'impiego del magnesio in terapia. Conv. Naz.: Il Magnesio: Aspetti
biochimici e clinici. Padova, Italy, October 26, p. 3-5. (1996)
ZATTA P.
Aspetti fisiopatologici dell'ipomagnesemia dell'anziano.IX Congr. Naz. Ordine dei Biologi: Alimenti,
Nutrizione e Cosmetici. Grado, Italy, October 10-13, p. 33-34. (1996)
(1997)
ZATTA P., ZAMBENEDETTI P.
The relevance of aluminum(III) speciation in the modulation of the activity of acetylcholinesterase,
Na+/K+-ATPase, carbonyc anhydrase and hexokinase. Conf.on Aluminium and Silicon in biology.
Keele University, U.K.,February 24-26. (1997)
ZATTA P., ZAMBENEDETTI P.
Aluminum and Biological systems: Effects on lysosomes. Intern. Symp. on Trace Elements in Humans:
New Perspectives. Athens, Greece, October 9-11, P.L.2. (1997)
TONINELLO A., ZATTA P.
60
Effect of aluminum on permeability transition of liver mitochondria. 42 o Congr. Naz. Soc. It. Bioch.
(SIB). Joint Symposia. Israel Society for Biochemistry and Molecular Biology and Società Italiana di
Biologia Sperimentale. Ancona, Italy, p. 247. (1997)
MORENO G., SALET C., RICCHELLI F.
Effects of Photodynamic Action on Cell Bioenergetics and Calcium Movements
7th Congress of the European Society for Photobiology , Stresa Italy, 8-13 September 1997,
Abs. S4
p.13 .
BARANYAI P., KATONA Z., RICCHELLI F., JORI G., BITTER I. GROFCSIK A., KUBINYI M.,
VIDOCZY T.
Meso-Tetraarylporphyrins as Molecular Probes of the Microenvironment
ibidem, Abs. P107, p. 121.
RICCHELLI F., GOBBO S., MORENO G., SALET C., BRANCALEON L., MAZZINI A.
Photophysical Properties of Porphyrin Planar Dimers
ibidem, Abs. P136, p.128.
VISONA’ A., YACOUB A., PAGNAN A., ANGELINI F., CALABRESE G., THIENE., GOBBO S.,
JORI G.
“Prevention of intimal hyperplasia by local delivery of a phthalocyanine photosensitizer”
7th Congress of the European Society of Photobiology (Stresa, Italy). Book of Abstracts, abstract O107,
1997
(1998)
BARBATO P., GOBBO S., SALET C., MORENO G., RICCHELLI F.
Porphyrin photodynamic action on Ca2+ transport in endoplasmic reticulum. A comparison with
mitochondria.
Convegno Annuale della Società Italiana di Fotobiologia, Desenzano (BS), 4-5 Aprile 1998.Abs. p.90.
RENKEN C., ERIKSSON O., RICCHELLI F., JORI G., BERNARDI P.
Photoactivated calcein generates reactive oxygen species (ROS) that are capable of changing Ca2+
accumulation dynamics in isolated rat liver mitochondria.
Biophysical Journal 74(2): A382-A382, Part 2 Feb 1998
ZATTA P., GIORDANO R., ZAMBENEDETTI P.
Metallothioneins are highly expressed in the astrocytes from Alzheimer's disease brain. VI Int. Conf.
on Alzheimer's Disease and Related Disorders. Amsterdam, The Netherlands, 18-23 July. Neurobiol.
Aging S50, p209. (1998)
ZATTA P., ZAMBENEDETTI P.
Effets of aluminum or tacrine on enzymatic activities of MAO A and B in neuroblastoma cells. VI Int.
Conf. on Alzheimer's Disease and Related Disorders. Amsterdam, The Netherlands, 18-23 July.
Neurobiol. Aging S118, p500 (1998)
ZAMBENEDETTI P., ZATTA P.
Metallothionein overexpression in astrocytes of Alzheimer's disease subjects. V AISETOV Natl. Conf.,
Bologna, Italy 25-26 September. (1998)
ZATTA P.
Aluminum(III) speciation and some biological effects on specific subcellular targets. COST D8 and
ESF WORKSHOP on Biological and Medicinal Aspects of Metal Ion speciation. K24. University.
JATE, Szeged Hungary, 23-25 August. (1998)
ZATTA P., DELL’ANTONE P., ZAMBENEDETTI P.
Anticholinesterasic drugs: tacrine, not physostigmine accumulates in intracellular acidic vesicles. VII
Congress of the Mediterranean Society of Clinical Pharmacology. Marrakech, October 28-30, C6.
(1998)
(1999)
RICCHELLI F., GOBBO S., MORENO G., SALET C.
Changes of membrane fluidity during the mitochondrial permeability transition as probed by
hematoporphyrin anisotropy
8th Congress of the European Society for Photobiology, Granada, Spain, 3-8 september 1999 Abs.
O77, p.112.
BEGHETTO C., GOBBO S., MORENO G., SALET C. RICCHELLI F.
Changes of fluidity of mitochondrial membrane induced by the permeability transition.
Congresso Annuale della Società Italiana di Fotobiologia, Pavia, 27-29 Maggio 1999. Abs. p. 29.
ZATTA P., ZAMBENEDETTI P.
61
Aluminum speciation and biological effects: Potential implications in human pathology. 5th Intern.
Symp. on Applied Bioinorganic Chemistry. Corfù, Greece, April 13-17 p. 205. (1999)
ANDRIANI M., NORDIO M., ZATTA P.
ACE Inhibitors (ACE-I) and angiotensin-II receptors antagonists (Ang II) in kidney protection. I Intern.
Congr. on Hypertension: From physiopathology to treatment. Fes, Moroccco, 28-30 October (1999)
ZATTA P., ZAMBENEDETTI P.
Aluminum neurotoxicity: implications in neurodegenerative diseases. 2nd Intern. Symp. on Trace
Elements in Human: New Perspectives. Athens, Greece 7-9 October, P.P.47. (1999)
(2000)
BEGHETTO C., RENKEN C., ERIKSSON O., JORI G., BERNARDI P., RICCHELLI F.
Generation of reactive oxygen species by photoactivated calcein. Implications for mitochondrial
studies. Photobiologie 2000, Aix-les-Bains, France, 26-27 May 2000 Abs
CAMERIN M., GOBBO S., SALET C., MORENO G., RICCHELLI F.
Changes of the fluidity of mitochondrial membranes during opening and resealing of the permeability
transition pore. Effects of the medium composition.
Photobiologie 2000, Aix-les-Bains, France, 26-27 May 2000 Abs
ZAMBENEDETTI P., ZATTA P.
Espressione delle metallotioneine nel cervello di mammiferi. VI Nat. Conf. A.I. S.E.T.O.V. Siena, Italy
17-19 February, pp. 19. (2000)
ZATTA P.
Aluminum neurotoxicity: implications in neurodegenerative diseases. 6th Intern. Symp. on Metal ions
in Biology and Medicine. Puerto Rico, 7-10 May. (2000)
ZATTA P.
Aluminum Neurotoxicity: Implications in Some Neurodegenerative Diseases. VI Intern. Symp. on
Metal Ions in Biology and Medicine. San Juan, Puerto Rico, 7-10 May, PL110 (2000)
ZATTA P., ANDRIANI M., ZAMBENEDETTI P.
Histopathological findings in the brain of uremic patients in dialysis. First International Conference on
Metals and the Brain: From Neurochemistryto Neurodegeneration. Padova 20-23 September 2000
J. Alzheimer's Disease vol.2, n.3-4: S1/17. (2000)
MOCCHEGGIANI E., GIACCONI R., CIPRIANO C., MUZZIOLI M., BERTONO-FREDDARI C.,
FATTORETTI P., CARPENE’ E., ZATTA P.
Metallothioneins as possible markers pf ageing. First International Conference on Metals and the
Brain: From Neurochemistry to Neurodegeneration Padova 20-23 September 2000. J. Alzheimer's
Disease vol.2, n.3-4: S2/2. (2000)
IBN LKHAYAT-IDRISSI M., MAZZEI P., ZATTA P.
In vivo and in vitro effects of Aluminum on acetylcholinesterase. First International Conference on
Metals and the Brain: From Neurochemistry to Neurodegeneration Padova 20-23 September 2000. J.
Alzheimer's Disease vol.2, n.3-4: S6/9. (2000)
ZAMBENEDETTI P., ROSSIPAL E., KARPF E., KLEINERT R., ZATTA P.
Expression of metallothionein I+II during human brain development. First International Conference on
Metals and the Brain: From Neurochemistry to Neurodegeneration. Padova 20-23 September 2000. J.
Alzheimer's Disease vol.2, n.3-4: P7. (2000)
CARPENE’ E., ZAMBENEDETTI P., ISANI G., WITTKOWSKI W., ZATTA P.
Presence of metallothioneins in bovine hypophysis. First International Conference on Metals and the
Brain: From Neurochemistry to Neurodegeneration. Padova 20-23 September 2000. J. Alzheimer's
Disease vol.2, n.3-4: P22. (2000)
(2001)
BEGHETTO C., CAMERIN M., GOBBO S., TOGNON G., SALET C., MORENO G., RICCHELLI
F.
Perturbation of the mitochondrial membrane structure by disaccharides.
Congresso Annuale Società Italiana di Fotobiologia, Pisa, 24-26 Maggio 2001. Abs. p. 45
CAMERIN M., POUSSIN K., GOBBO S., MORENO G., RICCHELLI F., SALET C.
The microenvironment of the sensitizer in mitochondrial membranes modulates the photodamage
induced by singlet oxygen: a study on the permeability transition.
Congresso Annuale Società Italiana di Fotobiologia, Pisa, 24-26 Maggio 2001. Abs. p. 45
BEGHETTO C., CAMERIN M., GOBBO S., TOGNON G., SALET C., MORENO G. RICCHELLI
F.
62
Reversibility Properties of the Ca2+-induced Permeability Transition in Mitochondria Suspende in
Saline and Sugar-containing Media.
IV International Symposium on “Photodynamic Diagnosis and Therapy in Clinical Practice”
Bressanone (Italy) 10-13 October 2001, Abs. P18.
ZATTA P., ZAMBENEDETTI P.
Metallothionein I-II in the developing human brain. SONA: 5 th Soc. Neurosc. Africa Intern. Conf.
Nairobi, Kenya 23-27 April. #65. (2001)
POLEC K., SZPUNAR J., LOBINSKI R.P., ZAMBENEDETTI P., ZATTA P.
Investigation of aluminum binding by neuroblastoma cells by hyphenated techniques. I Intern. Conf.
FESTEM, Venice, Italy P.3.14. (2001)
ZATTA P., ROSSIPAL E., KARPF E., KLEINERT R., ZAMBENEDETTI P.
Expression of metallothioneion I-II in the human brain. I Intern. Conf. FESTEM, Venice, Italy P.3.14.
(2001)
ZATTA P., ZAMBENEDETTI P.
Metallothioneins-I-II expression in some human neurodegenerative disorders, XIV Int. Congr. Polish
Pharmacol. Soc. Krakow 10-13 September, pp. 82-83. (2001)
ZAMBENEDETTI P., ROSSIPAL E., KLEINERT R., KARPF E., ZATTA P.
Metallothionein I-II in the human brain. 3rd Intern. Sympos. On Trace Elements in Humans: New
Perspectives. Athens 4-6 October, pp- 75. (2001)
Reviews and Books Chapter
Salvato B., Beltramini M.
Hemocyanins: molecular structure and reactivity of the binuclear copper site. Life Chem. Rep. 5, 249275 (1987).
Salvato B., Beltramini M.
Hemocyanins: molecular architecture, structure and reactivity of the binuclear copper active site. Life
Chem. Rep. 8, 1-47 (1990).
Salvato B., Beltramini M.
The functional asymmetry of the hemocyanin binuclear copper site. In "Lectures in Bioinorganic
Chemistry" (Nicolini, M. and Sindellari, L., eds.) Cortina International Raven Press, New York, pp.
139-157 (1991).
Banks W. , A. Kastin A. and Zatta P.
The Blood-Brain Barrier in Aluminium Toxicity and Alzheimer's Disease. In: Non-neuronal cells in
Alzheimer's disease. Zatta P. and Nicolini M. [Eds]. World Scientific, Singapore, London, pp 1-12.
(1995)
Pizziuti A., Zambenedetti P. and Zatta P.F.
La tossicità dell'alluminio nell'ambiente acquatico. In: Argomenti di Idrobiologia e Acquacoltura.
Carpenè E., Isani G. and Serra R. [Eds]. CLUEB, Bologna, pp 249-262. (1995)
Ricchelli F.
Photophysical properties of porphyrins in biological membranes . J. Photochem. Photobiol. B : Biol.
29 : 109 - 118 (1995).
Corain B., Bombi G.G., Tapparo A., Perazzolo M. and Zatta P.
Aluminum toxicity and metal speciation: Clear data and open questions. In: Aluminium Chemistry.
Corain B., Zatta P., Bombi G.G. and Nicolini M. [Guest eds]. Coord. Chem. Rev. (Special issue) 149:
11-22. (1996)
Kiss T., Zatta P. and Corain B.
Interaction of aluminum(III) with phosphate-binding sites: biological aspects and implications. In:
Aluminium Chemistry. Corain B., Zatta P., Bombi G.G. and Nicolini M. [Guest eds]. Coord. Chem.
Rev. (Special issue) 149: 329-346. (1996)
Harris W., Berthon G., Day P., Exley C., Flaten T.D., Forbes W., Kiss T, , Orvig C. and Zatta P.F.
Speciation of aluminum in biological system. J.Toxicol. Environm. Health 48: 543-568.
Lovell M., Ehmann W.D., Markesbery W.R., Melethil S., Swyt C.R. and Zatta P.F.
Aluminum biological standards: What are the needs? J.Toxicol. Environm. Health 48: 637-648. (1996)
Zatta P. and Zambenedetti P.
Aluminum(III) speciation and biological effects: Implications in human and experimental toxicity. In:
Cytotoxic, Mutagenic and Carcinogenic Potential Heavy metal Related to Human Environment. (N.D.
Hadjiliadis, ed.) NATO-ASI Series, 2. Environment-vol.26, pp. 231-240. (1997)
Zatta P. and Zambenedetti P.
63
Aluminum toxicity depends on the metal speciation. In: Aluminium Toxicity in Infants' Health and
Disease. Zatta P. and Alfrey A.C., eds. World Sc. Publ. Singapore, p. 40-53. (1997)
Zatta P. and Suwalsky M.
Aluminium, Membranes and Alzheimer’s disease. In: Aluminium and Alzheimer’s disease. The
science that Descibes the Link. C. Exley Ed.. Elsevier Science, Amsterdam, Holland, pp. 279-291.
(2001)
Hidalgo J, Aschner M., Vasak M., Zatta P.
Role of metallothionein family of proteins in the central nervous system. Brain Res. Bull. 55: 133-146.
(2001)
Mocchegiani E., Giacconi R., Cipriano C., Muzzioli M., Fattoretti P., Bretoni-Freddari C., Isani G.,
Zambenedetti P., Zatta P.
Zinc-bound metallolthionein as potential markers og ageing. Brain Res. Bull. 55: 147-154. (2001)
Zatta P., Suwalsky M.
Aluminum, Membranes and Alzheimer’s Disease. In: Aluminium and Alzheimer’s disease: The
Science that Describes the Link. C. Exley, Ed. Elsevier, Holland, pp. 279-291. (2001)
Books and Special Issues
GHIRETTI, F. Fisiologia Generale e Animale. Vol. I, UTET, Torino (197).8
GHIRETTI, F., ALBERGONI, V.Fisiologia Generale e Animale.Vol. II, UTET, Torino (1982).
GHIRETTI, F., CARIELLO, L. Le biotossine degli organismi marini. Piccin Ed., Padova.
GHIRETTI, F., DONATELLI, L., RUSSO, A. (a cura di) Filippo Bottazzi: Leonardo Scienziato.
Gianni Editore, Napoli (1986).
ZATTA, P. I fitofarmaci in Agricoltura: pensare a scelte strategiche per una agricoltura ambientale.
Francisci Editore, Abano, pag. 144 (1986).
NICOLINI M., ZATTA P., CORAIN B. (Eds) Aluminum in Chemistry Biology and Medicine.
Cortina International, Verona, and Raven Press, New York. pp. 117 . (1991)
ZATTA P., SNIDER A. (Eds) Research on age-related phenomena, neurodegeneration and
neuropathology. (Book of Abstracts). III International Conference on Alzheimer's Disease and Related
Disorders. Neurobiol. aging. vol. 13, Suppl. l (1992)
CORAIN B., IQBAL K., NICOLINI M., WINBLAD B., WISNIEWSKI H.M., ZATTA P. (Eds)
Alzheimer's disease: Clinical advances and basic research. J. Wiley and sons. Chichester, U.K. (1993)
NICOLINI M., CORAIN B., ZATTA P. (Eds.) Alzheimer's Disease and Related Disorders. Oxford,
Pergamon Press. pp. 474 (1993)
NICOLINI M., ZATTA P. (Eds.) Glycobiology and the Brain. Oxford, UK, Pergamon Press, pp. 293.
(1993)
NICOLINI M., ZATTA P., CORAIN B. (Eds) Aluminium in Chemistry Biology and Medicine. vol. 2.
Life Chemistry Reports (Special issue), Harwood Publ., London, pp. 270. (1994)
JORI G., POTTIER R.H., RODGERS M.A.J., TRUSCOTT T.G. (Eds) Photobiology in Medicine
NATO ASI Series A272, Plenum Press, New York, pp. 190 (1994)
JORI G., MOAN J., STAR W.M. (Eds) Photodynamic Therapy of Cancer , Proc. SPIE 2078,
Bellingham, Washington, pp. 564 (1994)
JORI G., PERRIA C. (Eds) Photodiagnostic and Phototherapeutic Techniques in Medicine Documento
Editoriale, Milano, pp. 165 (1995)
NICOLINI M. (Eds) Non-neuronal cells in Alzheimer's disease. World Scientific. Singapore, London
pp. 232. (1995)
CORAIN B., BOMBI G.G., NICOLINI M., ZATTA P. Aluminum chemistry. Coordination
Chemistry Reviews (Special issue) 149, pp. 404. (1996)
HONIGSMANN H., JORI G., YOUNG A.R. (Eds) The Fundamental Bases of Phototherapy , OEMF,
Milano, pp. 289 (1996)
EHRENBERG B., JORI G., MOAN J. (Eds) Photochemotherapy: Photodynamic Therapy and Other
Modalities, Proc. SPIE 2625, Bellingham, Washington, pp. 564 (1996)
JORI G., KARU T.I. (Eds) Effects of Low-Power Light on Biological Systems II , Proc. SPIE 2929,
Bellingham, Washington, (1996)
KOSTRON H., JORI G. (Eds) Special issue: Perspectives in Photodynamic Therapy , J. Photochem.
Photobiol., B:Biol. 36(2) (1996), Elsevier, Lausanne
ZATTA P., ALFREY A.C. (Eds) Aluminum in Infants' Health and Nutrition. World Scientific,
Singapore, London, pp. 270. (1997)
HONIGSMANN H., KNOBLER R. M., TRAUTINGER F., JORI G. (Eds) Landmarks in Photobiology
, OEMF, Milano, pp. 529 (1998)
64
ZATTA P., ZAMBENEDETTI P. Lectins, microglia and Alzheimer' disease. In: Lectins and Pathology
(M. Caron and A-P. Sève, eds) Hardwood Acad. Publ., Amsterdam, The Netherlands, pp. 35-49.
(1999)
ZATTA P., (Ed.) J. Alzheimer's Disease 2 pp. 1-81 (2000) Abstracts of the First Int.Conf. on: "Metals
and the Brain: from Neurochemistry to Neurodegeneration"
International Projects
Bilateral Projects ( Italy / USA ) :
a) Biophysical characterisation of copper sites type 3
b) Study of binding sites of metalloproteins through isomorphic substitution
Bilateral Projects ( Italy / Germany ) :
a) Interaction between metal active site and proteic matrix in copper proteins
b) Interaction between metalloproteins and exogenous ligands
1986 –1988 Bilateral Projects ( Italy / France ):
Utilization of liposomes as carriers of porphyrins in the tumor phototherapy. Collaboration with
Laboratoire de Photophysique Moléculaire, Universitè de Paris Sud, Orsay - France.
1988 -1991 Bilateral Projects ( Italy / France ):
Correlation between the subcellular distribution of porphyrins and phthalocyanines and their
photophysical and photosensitizing properties. Laboratoire de Biophysique, CNRS et INSERM,
Muséum National díHistoire Naturelle, Paris, France.
1988 -1990 Common Research Programs CNR / Bulgaric Academy of Sciences
Biochemical, Biophysical and Biotechnological Aspects of Metalloenzymes.
Bilateral Projects ( Italy / Germany )
Osmotic properties of hemocyanin. Hanstalt Helgoland, Hamburg, Germany
1990-1994 Bilateral Projects ( Italy / USA )
Lectin chemistry and applications. Department of Biochemistry of University of Athens, Georgia, USA
1991-1993 Common Research Programs CNR / Accademia Bulgara delle Scienze:
Functional and Structural Studies on Hemocyanins.
1992-1999 Common Research Programs CNR / Accademia Russa di Medicina
Copper Metabolism and Copper Proteins.
1992 -1993 Bilateral Projects ( Italy / France ):
Studies of photodynamic effects on the function and structure of cell membranes. Collaboration with
Dr. Christian Salet , Laboratoire de Biophysique, CNRS et INSERM, Muséum National d’Histoire
Naturelle, Paris, France.
1992-1996 ENEA, Antartica:
Molecular Physiology of oxygen in aquatic invertebrates
1994 -1995 Bilateral Projects ( Italy / France ):
Photodynamic effects on cell physiology: bioenergetics, calcium transport and cell growth. Laboratoire
de Biophysique, Muséum National d’Histoire Naturelle, Paris, France.
1995 –1997 Common Research Programs CNR / Bulgaric Academy of Sciences:
Photobiological mechanisms of photodynamic therapy. Institute of Organic Chemistry, BAN, Sofia.
1995-1997 Bilateral Projects ( Italy / UK )
Aluminum neurotoxicity Robens Institute, University of Surrey, Guilford, Surrey, UK (ZattaA.Taylor)
1996 -1999 Bilateral Projects ( Italy / France ):
Intracellular photosensitization: photodynamic effects on mitochondria and endoplasmic reticulum.
Laboratoire de Biophysique, CNRS et INSERM, Muséum National d’Histoire Naturelle, Paris, France.
1998-2000 Common Research Programs CNR / Bulgaric Academy of Sciences:
Mapping the Tryptophan Distribution in Multityrptophan Proteins.
1997-1999 Antartica:
Respiratory function in animals adapted to low temperature: Physiological aspects and Biotecnological
applications
1999 -2001 Antartica:
Development of biosensors utilizing metalloproteins
1999 - 2002 Scientific Cooperation Projects
Development of monoclonal antibodies against aluminum. Faculty of Chemistry, University of
Concepcion, Chile. Department of Biotechnology, University of Tel Aviv, Israel
2001 Short-term visits
Physiological aspects of titanium. Department of Biochemistry, University of Budapest, Hungary
65
2002-2004 Antartica
National Projects
CNR Strategic Projects:
Chemistry of Biological Processes. Chemical Methodologies supplied to the Study of Relevant
Biological Phenomena
National Project – M.P.I. 40%:
Mechanisms of cellular regulation
National Project – M.P.I. 40%:
Bioinorganic studies on metallic derivatives and organometallic compaunds
Co Fin - MURST
Supramolecular organisation and functional regulation of oligomeric proteins
International Collaborations
Biochemistry, University of Budapest, Hungary
CYTOPHARM, Palo Alto, California, USA
Department of Biochemistry, University of Georgia, Athens, GA, USA
Department of Biology, University of Utah at Salt Lake City, USA
Departamento de Biologia, Universidad Autonoma de Madrid, Spain
Department of Biophysics and Physiology, Yeshiva University, New York (USA)
Department of Chemistry, Bulgarian Academy of Sciences, Sofia, Bulgaria
Department of Chemistry, Hungarian Academy of Sciences, Budapest, Hungary
Department of Chemistry, University of Ohio at Bowling Green, USA
Department of Environmental Sciences, …Stefan, Ljubljana, Slovenia
Department of Inorganic Chemistry, University of Crete, Greece
Department of Inorganic Chemistry, University of Szeged, Szeged, Hungary
Department of Inorganic, Metallorganic and Analytical Chemistry and Department of
Department of Molecular Biophysics, University of Mainz (GE)
Departamento de Quimica, Universidad de Buenos Aires, Argentina
Departamento de Quimica, Pontificia Universidad Catolica, Santiago de Chile, Chile
Illinois Institute of Technology, Chicago, USA.
Institut for Experimental Medicine, RAMS, St. Petersburg
Institute of Organic Chemisty and Bulgarian Academy of Sciences.
Institut for Physiological Chemistry, University of Tubingen
Institute of Zoology, University of Munich, Germany.
Laboratoire pour l’Utilisation du Rayonment Electromagnetique, Paris (FR)
Laboratoire de Biophysique, CNRS et INSERM, Musèum National d'Histoire Naturelle, Paris, France.
Laboratoire de Photophysique Molèculaire , Universitè de Paris-Sud , Orsay, France.
Max-Planck Institut für Strahlenchemie, Mülheim/Ruhr, Germany
Robens Institute, University of Surrey, Guilford, UK
National Collaborations
Clinical Medicine Vascular Pathology Unit, Padova.
CNR Center of Pharmacological Chemistry, Department of Pharmacological Sciences University of
Padova.
CNR Center of Quantum Electronic, Institute of Physics, University of Firenze.
CNR Center of Quantum Electronic, Polytechnic of Milano.
Department of Anatomopathology, General Hospital, Dolo, Venezia.
Department of Experimental Biomedical Sciences, University of Padova.
Department of General Chemistry, University of Pavia.
Department of General Chemistry, University - La Sapienza – Roma.
Department of Geriatrics, General Hospital, Dolo, Venezia.
Department of Immunology, University of Bologna.
Department of Inorganic Chemistry, University of Firenze.
Department of Nefrology and hypertension, General Hospital, Dolo, Venezia.
Department of Neurosciences, University “Tor Vergata”, Roma.
Department of Organic Chemistry, University of Padova.
66
Department of Pharmacology, University of Padova.
Department of Biological Chemistry, University of Parma.
Department of Physics, University of Ancona.
Department of Physics, University of Parma.
Department of Physics, University of Palermo.
Division of Radiotherapy, Padova general Hospital.
Department of Veterinary Pathology University of Padova
INFNM – Biophysic section and Department of Physics, University of Parma
INFN National Laboratories, Frascati
INRCA, Ancona
MOLTENI Farmaceutici, Firenze
Neurosurgery Clinic, University of Sassari.
Organization of International and National Conferences
1992 Colloquia Patavina on Aluminum in Chemistry, Biology and Medicine. Padova.
1992. III International Conference on Alzheimer’s Disease and Related Disorders.Padova.
1994 Colloquia Patavina on Aluminum in Chemistry, Biology and Medicine. Padova.
1997 Magnesium: Biochemistry and Clinical Aspects. Padova
1996 XI International conference on supramolecular organization and functional regulation of
invertebrate dioxygen binding proteins. Padova.
2000 Metals and the Brain: From Neurochemistry to Neurodegeneration. Padova
Theses
1976/77
Denaturazione con urea dell’emocianina di Carcinus moenas
C. Sconfienza.
La composizione in aminoacidi delle emocianine: studi comparativi.
Mariano Beltramini.
1978/79
Dissociazione dell’Emocianina di Helix pomatia in presenza di urea a bassa concentrazione e
ricostituzione dell’Emocianiona di Carcinus maenas con complessi del Cu e del Co
Maria Beatrice Sfrappini.
1979/80
Osservazioni comparative sull’ Emocianina di alcuni crostacei
Maria Letizia Piccoli.
1980/81
Caratterizzazione dell’Emocianina di Squilla mantis.
Tiziana Pianca.
Studi comparativi su serin proteasi batteriche tipo subtilisine
G. Cappozzo.
Influenza di alcuni sali neutri sulla deramazione e ricostituzione dell’emocianina
A.Viale.
Osservazioni su clorocruorina di Spirographis spallanzani.
S. Bonavoglia.
1982/83
Proprietà di fluorescenza di alcuni derivati di emocianina di Octopus vulgaris
L. Bellinato.
Studi sull’intorno del triptofano in sistemi modello e subtilisine mediante spettroscopia di fluorescenza
G. Oradini.
Relazioni struttura-funzione in subtilisine
M. Manzano.
Preparazione di derivati di emocianina di Octopus vulgaris.
Marcello Alviggi.
1984/85
Cinetica d iricostituzione dell’emocianina di Carcinus maenas con Cu (I) in presenza di SCN-.
Giulio Moriondo.
Studi spettroscopici sul derivato a cobalto dell’emocianina di Carcinus maenas.
Anna Maria Racioppa.
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1985/86
Studi spettroscopici sulla interazione dell’ematoporfirina con sistemi microeterogenei
D. Stevanin.
Derivati ossidati di emocianina.
Gianfranco Zilio.
Effetto di alcoli, di Ca2+ e di Mg2+ sulla reazione tra emocianina di Carcinus maenas e CN-.
Meri Santamaria.
1986/87
Interazione tra emocianina di Octopus vulgaris e CO.
Monica Squitieri.
Preparazione e caratterizzazione del derivato binucleare a cobalto dell’emocianina di Carcinus maenas.
Anna Mazzucato.
Facoltà di Scienze, Laurea in Scienze Biologiche
Sperimentazione tossicologica con composti idrofili e lipofili di Alluminio (III)
Mosé Favarato.
1987/88
Studi spettroscopici e fotocinetici su un derivato dell’ematoporfirina
G. Gambaro.
Studi spettroscopici su sistemi liposomi-porfirine
T. Cavalieri.
Modelli chimici e biologici di tossicità da metalli: Tris-(2,4-pentandionato) alluminio (III):
Proprietà delle soluzioni acquose, n-ottanoliche e liposomiche e tossicologia sul coniglio (Oryctolagus
cuniculus)
Maurizio Perazzolo.
Modelli chimici e biologici di tossicità da metalli: Ruolo della speciazione dell’alluminio (III) nella sua
azione biologica in vivo e in vitro
Laura Fontana.
Effetti idrolitici di estratti di epatopancreas sull’emocianina di Octopus vulgaris.
Renzo Carletti.
Cobalto-derivati dell’emocianina di Carcinus maenas
1988/89
Attività pseudo-enzimatiche dell’emocianina di Octopus vulgaris.
Graziella Turato.
Interazioni di agenti fotosensibilizzanti con modelli di membrana
M. Tronchin.
1989/90
Reazione dell’emocianina di Octopus vulgaris con floruro.
Reazione tra emocianina di Octopus vulgaris ed azide.
Alessandra Giassi.
1991/1992
Il rame e l’ossigeno nel sito attivo delle emocianine.
Andrea Maso.
Effetti allosterici nella reazione di scambio O2-SCN- dell’emolinfa di molluschi.
Enrico Danese.
Proprietà di luminescenza dell’emocianina.
Anna Favero.
Fotosensibilizzazione di mitocondri mediante porfirine legate a liposomi
G. Bianco
1992/93
La reazione tra emocianina di Carcinus maenas e nitrito.
Carla Bertolli.
Coinvolgimento di superossido dismutasi e catalasi nel metabolismo del metanolo nei lieviti.
Monica Facco.
Studio della luminescenza nella reazione tra CuZnSOD e perossido d’idrogeno.
Simona Zanni.
Studi strutturali e funzionali sull’eterogeneità molecolare dell’emocianina di Carcinus maenas.
Silvia Franzin
Modelli chimici e biologici di tossicità da metalli: Studio NMR dell’interazione dell’alluminio(III) con
fosfolipidi e membrane eritrocitarie
Pamela Zambenedetti
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Modelli chimici e biologici di tossicità da metalli: Effetto della speciazione dell’alluminio(III) in
colture di neuroblastoma murino
Sara Masiero
Fotosensibilizzazione di mitocondri ad opera di ftalocianine
V. Palumbo.
1993/94
Rilevamento in continuo della funzione di saturazione delle’emocianina con ossigeno.
Barbagallo Marco.
Preparazione e caratterizzazione di un derivato a Cu(II) dell’emocianina di Carcinus maenas.
Francesca Gennari.
Distribuzione di porfirine e ftalocianine in membrane mitocondriali
E. Cumerlato Stiffan.
1994/95
Effetti della fotosensibilizzazione con porfirine sul trasporto del Ca2+ in organelli subcellulari
M. Milani.
Effetti della Tacrina su cellule di neuroblastoma murino
Beatrice Marturano.
Caratterizzazione chimico-fisica dell’emolinfa di Carcinus maenas e di Trunculariopsis trunculus
Carmelo Calia.
1994/95
Caratterizzazione delle subunità strutturali dell’emocianina di Carcinus maenas
Caterina Migale.
Reazione dell’azide con derivati ossidati dell’emocianina di Carcinus aestuarii.
Annarita Gambalonga
Modelli chimici e biologici per lo studio della tossicità dell’alluminio (III): importanza della
speciazione del metallo
Valeria Bruno
1995/96
Effetti della fotosensibilizzazione con porfirine sul trasporto del Ca2+ in mitocondri
P. Barbato
Effetti dell’alluminio e tacrina su alcuni sistemi enzimatici
Cristiano Cagnolini
Reazioni di emocianina di Rapana thomasiana con ossidanti bielettronici.
Roberta Rosin
1996/97
Preparazione e caratterizzazione di derivati dell’emocianina di Octopus vulgaris contenenti Co(II).
Maria Antonia Lonuzzo.
Eterogeneità strutturale e funzionale dell’emocianina di Paralithodes camtschaticae
Annamaria Molon
Reazione di ossidazione di emocianine con nitriti e ossidi di azoto.
Paolo Fioraso
Emocianina di Paralithodes camtschaticae: caratteristiche strutturali e funzionali Neurotossicità dello
stagno
Cristina Cavalieri
L’uso del magnesio nella citofilassi e nella pratica clinica
Annalisa Coppola
Proprietà fotofisiche di aggregati planari di porfirina
S. Resoli
Aspetti fisiopatologici del magnesio in urologia e nefrologia
Stefano Tulio
Effetti dell’alluminio sul metabolismo del calcio intracellulare
Luisella Gandolfi
Effetti dell’alluminio su alcuni enzimi lisosomiali
Luca Bordon
Effetti dell’alluminio su cellule ematiche
Annarita Chimenton
Effetti Biologici dell’alluminio e della tacrina su cellule di neuroblastoma murino
Valentina Nicosia
Aspetti tossici dell’alluminio in pediatria
Mason Paola
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Effetto pro-ossidante dell’alluminio in linfociti umani ed in cellule di neuroblastoma murino
Greta Zannini
Aspetti fisiopatologici e farmacologici del magnesio nelle emicranie.
Laura Sartori
1997/98
Depolimerizzazione di emocianine di molluschi indotta da metalli della prima serie di transizione.
Michela Paccagnella
Studi preliminari sull’impiego dell’emocianina di Carcinus aestuarii come biosensore per l’ossigeno.
Marta Marangotto
Caratterizzazione spettroscopica e funzionale della tirosinasi di Streptomyces antibioticus.
Maria Chiara Ferrarese
Effetti della fotosensibilizzazione con porfirine sul trasporto del Ca 2+ in reticolo endoplasmatico e
mitocondri
U. Fronzoni
Il sovraccumulo di ferro ed alluminio nel morbo di Parkinson: alcuni modelli di studio
Margherita Milanese.
1998-99
Variazioni della fluidità delle membrane mitocondriali indotte dalla transizione di permeabilità
C. Beghetto
Modelli biologici per lo studio di effetti farmacologici della melatonina: possibili implicazioni in
alcune patologie neurodegenerative.
Stefania Rosan
Ruolo della struttura terziaria nel definire la funzionalità dei siti binucleari a rame.
Silvia Campello
Caratterizzazione strutturale e funzionale dell’emocianina di Penaeus monodon.
Carlo Bidona
Effetti biochimici dell’alluminio (III) sullle piastrine umane: possibili implicazioni nella malattia di
Alzheimer ed in altre patologie neurodegenerative
Aurelio Garofano
Modelli biochimici e biofisici per lo studio della neurotossicità dell’ Al (III): possibili implicazioni in
alcune patologie neurodegenerative
Enzo Lain
1999/2000
Effetto dell’ossigeno di singoletto sulla transizione di permeabilità mitocondriale:influenza del
microintorno del fotosensibilizzatore
M. Camerin
Variazioni indotte dal potenziale di membrana sulla fluidità delle membrane mitocondriali e loro
modulazione da parte della composizione del mezzo
M. Cescon
Studio funzionale e strutturale del meccanismo di inibizione dei mercaptani sulla tirosinasi.
Andrea Mardegan
Studio delle proprietà di proteine respiratorie in matrici solide.
Alessandro Cestaro
2001/2002
Proprietà biochimiche della melatonina in vivo e in vitro
Paolo Carampin
Studi in vivo sulle proprietà biochimiche delle metallotioneine
Cristina Di Pisa
PhD Theses
PhD Theses carried out using space, services and instruments of the CNR Center undre supervision of
University Professors members
Fisiologia molecolare della superossido dismutasi a rame e zinco in colture cellulari di lieviti (Dott.
Paolo Romandini. (Dottorato di Ricerca in Biologia Evoluzionistica III ciclo)
Aspetti biofisici e biochimici del sito binucleare a rame di tipo 3 (Dott Meri Santamaria. Dottorato di
Ricerca in Biologia Evoluzionistica X ciclo)
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Struttura di macromolecole biologiche complesse (Dott. Caterina Santini. Dottorato di Ricerca in
Biologia Evoluzionistica VII ciclo)
Superossido dismutasi a rame e zinco in lieviti e batteri (Dott. Gianfranco Santovito. Dottorato di
Ricerca in Biologia Evoluzionistica IX ciclo)
Sistemi coinvolti nel trasporto dell’ossigeno: adattamento alle basse temperature nell’ambiente marino
(Dott. Elisa Angelini.- Dottorato di Ricerca in Biologia Evoluzionistica X ciclo)
Ruolo della struttura terziaria e quaternaria nella funzione di proteina a rame (Dott. Enrico Dainese.
Dottorato di Ricerca in Biologia Evoluzionistica X ciclo)
Study of evolutionary srategies of hemocyanins, invertebrate oxygene transport proteins (Dott.
Annalaura Sabatucci. Dottorato di Ricerca in Biologia Evoluzionistica XII ciclo)
Struttura quaternaria delle emoglobine extracellulari degli anellidi: la clorocruorina di Sabella
Spallanzani (Gmelin, 1971) (Dott. Alberta Casagrande. Dottorato di Ricerca in Biologia
Evoluzionistica XIII ciclo)
Fisiologia molecolare di proteine con siti di nucleari (Dott. Stefano Vanin. Dottorato di Ricerca in
Biologia Evoluzionistica XIV ciclo)
AKNOWLEDGEMENTS
I would like to thank Professor M. Beltramini, G. Jori and F. Ricchelli for their contribution for the
presentation of this report.
I would like to thank also D. Cervellin for the technical support for the preparation of the present
booklet and G. Tognon for the e. m. pictures.
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