Thioredoxin activates MKK4-NFκB pathway in a redox-dependent manner to control manganese superoxide dismutase gene expression in endothelial cells

Abstract

Background: The mechanism underlying thioredoxin-induced expression of manganese superoxide dismutase (MnSOD) is unknown. Results: Reduced thioredoxin activates the MKK4-NFκB pathway to repress MKK7-AP-1-mediated inhibition of MnSOD expression. Conclusion: Cellular redox status regulates gene expression via redox control of MKK4, an MAPK. Significance: This study reveals a novel mechanism underlying transcriptional regulation of MnSOD encoding a critical antioxidant enzyme.