APOPTOSIS:
By Dan Matthew Espinoza Burias
Definition/Trivia
Characteristics
Significance
Factors
Apoptosis VS Necrosis
Molecular Machinery
Molecular Mechanisms
Disease
Definition/Trivia
Derived from the Greek word for a natural process of leaves
falling from trees or petals from flowers
A distinct form of Programmed Cell Death (Type I)
An active, metabolic, genetically encoded and evolutionary
selected death pathway
As many as 1011 cells die in adult human per day
Billions of cells die every hour in the bone marrow and
intestines
Characteristics/Manifestations
 Membrane Blebbing
 Loss of Cell Symmetry and Attachment
 Cell Shrinkage
 Nuclear Fragmentation (karyorrhexis)
 Chromatin condensation (pyknosis)
 Chromosomal DNA fragmentation (evident in gel
electrophoresis)
 Overall change in Cytomorphology
Apoptosis in ACTION!
Apoptosis VS Necrosis
Apoptosis VS Necrosis
Apoptosis VS Necrosis
Apoptosis VS Necrosis
Apoptosis VS Necrosis
Factors
Intrinsic
Extrinsic
Cellular Oxidative Stress
Glucocorticoids
Heat
Radiation
Nutrient Deprivation
Viral Infection
Hypoxia
Extremely high Cytosolic
Calcium ion levels
Genetic Damage
Toxins
Hormones
Growth Factors
Nitric Oxide
Cytokines (Positive or
Negative Induction)
Significance: Physiologic
Programmed destruction of cells during Embryogenesis
Involution of hormone-dependent tissues upon hormone
deprivation
Cell loss in proliferating cell populations
Elimination of cells that have served their useful purpose
Elimination of potentially harmful self-reactive lymphocytes
Cell death induced by Cytotoxic T lymphocytes
Significance: Pathologic
 DNA Damage
 Cell injury in certain infections
 Pathologic atrophy in parenchymal organs after duct
obstruction
Molecular Machinery: Caspases
Caspases – cysteine-aspartic protease or Cysteinedependent Aspartate-directed proteases
- essential cysteine proteases in mediating
apoptosis
2 Types:
Initiator caspases – CASP2, CASP 8, CASP 9 and CASP10;
activates other caspases (executioner caspases)
Executioner Caspases – CASP3, CASP6 and CASP7; digests
other proteins in the cell (Cytoskeleton and Nuclear
Lamins)
Molecular Machinery: Bcl-2 Family
Bcl – 2 Family – main proteins that regulate the activation
of caspases
Types:
Pro-apoptotic proteins – Bax and Bak
Anti-apoptotic proteins – Bcl –xL,
Bcl – 2 and Bcl- w
BH3-only proteins (sensor proteins) – Bid, Bad, Bim and
Puma
Bcl-2 Family in ACTION!
Molecular Machinery: Inducers
Tumor Necrosis Factor alpha (TNFɑ)
Fas Ligand (FasL)
Transforming Growth Factor Beta (TGFß)
Bax (and other proapoptotic Blc-2 family members)
Glucocorticoids
Also, aberrant expressions of:
Oncogenes (e.g. c-myc)
Normal tumor suppressor gene function (such as p53)
Molecular Mechanisms:
Intrinsic/Mitochondrial Pathway
Molecular Mechanisms:
Intrinsic/Mitochondrial Pathway
Molecular Mechanisms:
Intrinsic/Mitochondrial Pathway
Molecular Mechanisms:
Extrinsic/Death Receptor Pathway
Molecular Mechanisms:
Extrinsic/Death Receptor Pathway
Molecular Mechanisms:
Extrinsic/Intrinsic Pathway
Elimination of Apoptotic Cell
Apoptotic cells are removed through efferocytosis by
phagocytic cells
Apoptotic cells are recognised by phagocytic cells by the
presence of phosphatidylserine in the extracellular surface
side of the plasma membrane
Phosphatidylserine is normally found in the cytosolic face of
the plasma membrane. During the final phase of apoptosis, PS
is translocated to the other side by the enzyme scramblase.
Apoptosis and Diseases
Excessive Cell Death can cause/is associated with:
Acquired Immune Deficiency Syndrome
Alzheimer's Disease
Parkinson’s Disease
Ischemic Injury (Myocardial Infarction)
Too little cell death can cause:
Cancer
Persistent Viral Infection
Autoimmune Disease
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