title: Stabilization of Nrf2 protein by D3T provides protection against ethanol-induced apoptosis in PC12 cells.
abstract: Previous studies have demonstrated that maternal ethanol exposure induces a moderate increase in Nrf2 protein expression in mouse embryos. Pretreatment with the Nrf2 inducer, 3H-1, 2-dithiole-3-thione (D3T), significantly increases the Nrf2 protein levels and prevents apoptosis in ethanol-exposed embryos. The present study, using PC12 cells, was designed to determine whether increased Nrf2 stability is a mechanism by which D3T enhances Nrf2 activation and subsequent antioxidant protection. Ethanol and D3T treatment resulted in a significant accumulation of Nrf2 protein in PC 12 cells. CHX chase analysis has shown that ethanol treatment delayed the degradation of Nrf2 protein in PC12 cells. A significantly greater decrease in Nrf2 protein degradation was observed in the cells treated with D3T alone or with both ethanol and D3T. In addition, D3T treatment significantly reduced ethanol-induced apoptosis. These results demonstrate that the stabilization of Nrf2 protein by D3T confers protection against ethanol-induced apoptosis.
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, North Carolina, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Dong
authors.forename: Dong
authors.initials: D
authors.lastname: Yan
authors.forename: Shao-Yu
authors.initials: SY
authors.lastname: Chen
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D019610:Cytoprotection / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical; D000431:Ethanol / Q000633:toxicity*; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D016716:PC12 Cells; D055550:Protein Stability / Q000187:drug effects; D051381:Rats; D013871:Thiones / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; D013871:Thiones; D013876:Thiophenes; D000431:Ethanol; C049325:1,2-dithiol-3-thione