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Enantiomers of Lipoic Acid Differentially Affect Nrf2
Activation
Kelly CrottyDr. Tory Hagen
Our bodies are under attack
from both external and
internal toxins.
•Transcription factor
• Binds to the Antioxidant Response Element (ARE)
•Influences over 200 genes with the ARE
•These genes produce detoxification enzymes and antioxidant proteins
Nrf2: A Transcription Factor
B zip
• Always being produced
• Almost immediately bound to the protein Keap1 and degraded
Nucleus
Cell
Nrf2 Production and Degradation
Nucleus
Cell
Nrf2 Activation
• Under stress, Nrf2 returns to the nucleus in greater
amounts to stimulate gene expression.
Lipoic Acid
• Lipoic Acid (LA) positively influences Nrf2-driven gene expression.
The Enantiamers of Lipoic Acid
How potent is S-LA compared to the commercially available racemic mixture or natural R-LA?
Question:
Methods:
Measure relative Nrf2 protein levels in the nucleus through western blot analysis
Isolate the nuclei of cells that have been treated with lipoic acid
Con
trol
5
0 uM
35
uM
20
uM
10
uM
5 uM
50 uM
20 uM
10 uM
5 uM
35 uM
100 kD
R-LA > R,S-LA > S-LA
in activating Nrf2
Implications:
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 AhernDr. Tory Hagen
Judy ButlerDr. Dove Keith
&Dr. Kate Shay, Eric Smith, Luis Gomez, Dr. Alex Michels,
Liam Finlay, Dr. Regis Moreau
and the rest of the Hagen lab