Cytoprotective role of Nrf2/Keap1 system in methylmercury toxicity

"primary mouse hepatocytes extracted from Nrf2-deficient mouse was susceptible, and hepatocyte-specific conditional Keap1-deficient mouse was resistant to MeHg-induced cytotoxicity"

Read more: CiteULike: Cytoprotective role of Nrf2/Keap1 system in methylmercury toxicity:

Nrf2, HSP90 and CFS - More Evidence of Increased Risk w Certain Ancestries~!

Backgound: In recent weeks we have discussed many health problems that may occur with impaired Nrf2 functioning. Past studies have also suggested that SNPs in Nrf2 which may be population specific and may increase oxidative stress in those individuals. One such SNP has been shown to be present in the Native American population and another study has suggested that while the data is limited there seems to be a significantly higher risk of chronic fatigue syndrome in Native Americans and African-Americans. It has also be suggested that HSP90 activity may be used as a marker for CFS in a past study.

Niture from the University of Maryland demonstrates that HSP90 is involved in the activity of the Nrf2. He writes that Keap1 is an adaptor for Nrf2 and that HSP90 is a stabilizer for Keap1 under stress. He reports that HSP90 interacts with this adaptor to activate Nrf2. This suggests that Nrf2 activity may be closely associated with the development of CFS and leads one to assume that mechanisms that improve the activity of Nrf2 may be beneficial for therapeutics for CFS which may have a higher incidence rate for individuals with specific ancestries.  

Read more: HSP90


Thambirajah, A. A., Sleigh, K., Stiver, H. G., and Chow, A. W. (2008). Differential heat shock protein responses to strenuous standardized exercise in chronic fatigue syndrome patients and matched healthy controls. Clinical and investigative medicine. Médecine clinique et experimentale, 31(6). http://www.citeulike.org/user/HEIRS/article/3725342
Niture, S. K. and Jaiswal, A. K. (2010). Hsp90 interaction with inrf2 (keap1) mediates stress-induced nrf2 activation. The Journal of biological chemistry. http://www.citeulike.org/user/HEIRS/article/7968348
Dinos, S., Khoshaba, B., Ashby, D., White, P. D. D., Nazroo, J., Wessely, S., and Bhui, K. S. S. (2009). A systematic review of chronic fatigue, its syndromes and ethnicity: prevalence, severity, co-morbidity and coping. International journal of epidemiology. http://www.citeulike.org/group/6033/article/4289419

CiteULike: Benzo[a]pyrene Increases the Nrf2 Content by Downregulating the Keap1 Message

CiteULike: Benzo[a]pyrene Increases the Nrf2 Content by Downregulating the Keap1 Message: "BaP, but not its metabolites, increases the amount of the nuclear Nrf2 protein by downregulating the Keap1 message in Jurkat cells"

Resveratrol Metabolites Induces HO-1 via Nrf2 through KEAP1 Residue Modification.

It is hence likely that piceatannol modifies specific cysteine residues of Keap1, which allows Nrf2 to translocate into the nucleus and bind to ARE, leading to enhancement of the expression of HO-1. The characteristic catechol moiety of piceatannol appears to be critical for induction of Nrf2 activation and subsequent upregulation of HO-1.

CiteULike: Piceatannol induces heme oxygenase-1 expression in human mammary epithelial cells through activation of ARE-driven Nrf2 signaling.: "Lee, H.-H. H., Park, S.-A. A., Almazari, I., Kim, E.-H. H., Na, H.-K. K., and Surh, Y.-J. J. (2010). Piceatannol induces heme oxygenase-1 expression in human mammary epithelial cells through activation of are-driven nrf2 signaling. Archives of biochemistry and biophysics."