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Alpha-lipoic acid regulates heme oxygenase gene expression and nuclear Nrf2 activation as a mechanism of protection against arsenic exposure in HepG2 cells
- Source :
-
Environmental Toxicology & Pharmacology . Mar2010, Vol. 29 Issue 2, p144-149. 6p. - Publication Year :
- 2010
-
Abstract
- Abstract: Oxidative stress is a known mechanism induced, among other things, by arsenic toxicity. As a response, the cell triggers the synthesis of antioxidant and stress response elements like glutathione and heme oxygenase. Alpha-lipoic acid (ALA) is a well-known antioxidant that confers protection to oxidative stress conditions. We analyzed the effect of ALA pretreatment on Nrf2-responsive gene expression of HepG2 cells exposed to As3+. Cells were treated with 5mM ALA and 8h later exposed to 50μM As3+ for 24h, analyzing MTT-activity, glutathione content, Nrf2 induction and antioxidant gene expression. As3+ increased glutathione (154%), heme oxygenase, glutamate cystein ligase, modifier subunit and metallothionein (35-fold, 10-fold and 9-fold, respectively). ALA prevented the strong expression of heme oxygenase by As3+ exposure (from 35- to 5-times of control cells), which correlated with the reduction of Nrf2 observed in As3+ group. ALA pretreatment can down-modulate the response mediated by Nrf2 and provide protection to As3+ exposed HepG2 cells. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 13826689
- Volume :
- 29
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Environmental Toxicology & Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 48219657
- Full Text :
- https://doi.org/10.1016/j.etap.2009.12.004