查看文章

Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) is the primary transcription factor protecting cells from oxidative stress by regulating cytoprotective genes, including the antioxidant glutathione (GSH) pathway. GSH maintains cellular redox status and affects redox signaling, cell proliferation, and death. GSH homeostasis is regulated by de novo synthesis as well as GSH redox state; previous studies have demonstrated that Nrf2 regulates GSH homeostasis by affecting de novo synthesis. We report that Nrf2 modulates the GSH redox state by regulating glutathione reductase (GSR). In response to oxidants, lungs and embryonic fibroblasts (MEFs) from Nrf2-deficient (Nrf2^−/−) mice showed lower levels of GSR mRNA, protein, and enzyme activity relative to wild type (Nrf2^+/+). Nrf2^−/− MEFs exhibited greater accumulation of glutathione disulfide and cytotoxicity compared to Nrf2^+/+ MEFs in response to t …