Enantiomers of Lipoic Acid
Differentially Affect Nrf2
Activation
Kelly Crotty
Dr. Tory Hagen
Our bodies are
under attack
from both
external and
internal toxins.
Nrf2: A Transcription Factor
•Transcription factor
• Binds to the Antioxidant
Response Element (ARE)
•Influences over 200
genes with the ARE
•These genes produce
detoxification enzymes
and antioxidant proteins
B zip
Nrf2 Production and Degradation
• Always being
produced
• Almost immediately
bound to the protein
Keap1 and degraded
Nucleus
Cell
Nrf2 Activation
• Under stress, Nrf2 returns
to the nucleus in greater
amounts to stimulate
gene expression.
Nucleus
Cell
Lipoic Acid
• Lipoic Acid (LA) positively
influences Nrf2-driven gene
expression.
The Enantiamers of Lipoic Acid
Question:
How potent is S-LA compared to
the commercially available
racemic mixture or natural R-LA?
Methods:
Isolate the nuclei of cells that
have been treated with lipoic
acid
Measure relative Nrf2 protein
levels in the nucleus through
western blot analysis
100 kD
50 uM
20 uM
10 uM
5 uM
35 uM
Implications:
R-LA > R,S-LA > S-LA
in activating Nrf2
Lipoic
Acid
Though R-LA and S-LA have
•similar
structure, they activate
Nrf2 at completely different
concentrations
Future Projects:
Continue the concentration curve until R,S-LA
•and
S-LA have also reached saturation
• Add more time points for the time course
• Repeat the time course with R-LA
Thank you to:
The HHMI Summer Research Program
Dr. Kevin Ahern
Dr. Tory Hagen
Judy Butler
Dr. Dove Keith
&
Dr. Kate Shay, Eric Smith, Luis Gomez, Dr. Alex Michels,
Liam Finlay, Dr. Regis Moreau
and the rest of the Hagen lab