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