1. Enantiomers of Lipoic Acid Differentially Affect Nrf2 Activation Kelly Crotty Dr. Tory Hagen

2. Our bodies are under attack from both external and internal toxins.

3. 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

4. Always being produced Almost immediately bound to the protein Keap1 and degraded Nucleus Cell Nrf2 Production and Degradation

5. Nucleus Cell Nrf2 Activation Under stress, Nrf2 returns to the nucleus in greater amounts to stimulate gene expression.

6. Lipoic Acid Lipoic Acid (LA) positively influences Nrf2-driven gene expression.

7. The Enantiamers of Lipoic Acid

8. How potent is S-LA compared to the commercially available racemic mixture or natural R-LA? Question:

9. 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

10. Control 50 uM 35 uM 20 uM 10 uM 5 uM 50 uM 20 uM 10 uM 5 uM 35 uM 100 kD

13. 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

14. 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

15. 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