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Stabilization of Nrf2 Protein by D3T Provides Protection against Ethanol-Induced Apoptosis in PC12 Cells 1 1 2 Jian Dong , Dong Yan , Shao-yu Chen * 1 Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, North Carolina, United States of America, 2 Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine, Peoria, Illinois, United States of America 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. Citation: Dong J, Yan D, Chen S-y (2011) Stabilization of Nrf2 Protein by D3T Provides Protection against Ethanol-Induced Apoptosis in PC12 Cells. PLoS ONE 6(2): e16845. doi:10.1371/journal.pone.0016845 Editor: Ted Dawson, Johns Hopkins, United States of America Received September 2, 2010; Accepted January 6, 2011; Published