Over-expression of Nrf2 diminishes ethanol-induced oxidative stress and apoptosis in neural crest cells by inducing an antioxidant response.

Nuclear factor erythroid 2-related factor (Nrf2) is a key transcription factor that regulates antioxidant defense in cells. In this study, we investigated whether over-expression of Nrf2 can prevent ethanol-induced oxidative stress and apoptosis in neural crest cells (NCCs). We found that transfection of NCCs with pcDNA3.1-Nrf2 resulted in statistically significant increases in the Nrf2 protein levels in control and ethanol-exposed NCCs as compared to the cells transfected with control vector. Luciferase reporter gene assay revealed that over-expression of Nrf2 significantly increased the antioxidant response element (ARE) promoter activity in NCCs. Nrf2 over-expression also increased the protein expression and activities of Nrf2 target antioxidants in NCCs. In addition, over-expression of Nrf2 significantly decreased ROS generation and diminished apoptosis in ethanol-exposed NCCs. These results demonstrate that over-expression of Nrf2 can confer protection against ethanol-induced oxidative stress and apoptosis in NCCs by the induction of an antioxidant response.