Sulfiredoxin is Regulated by NRF2 During Oxidative Stress in Lungs

TL;DRAbstract

Mammalian sulfiredoxin (SRX) plays a role in the regulation of oxidative stress. However, the transcriptional regulation of SRX in response to oxidative stress is not clear. Here we demonstrated that NRF2 transcription factor regulates SRX expression following oxidative stress in lungs. In response to cigarette smoke exposure, lungs from wild‐type mice showed significant increase in the mRNA and protein expression of SRX, while no induction was observed in lungs from NRF2‐/‐ mice. Similarly, diquat‐induced oxidative stress resulted in increased expression of SRX in wild‐type mouse embryonic fibroblasts (MEF), but not in the NRF2‐/‐ MEF cells. Silencing SRX by siRNA induced greater generation of ROS in Raw 264.7 macrophages. Promoter analysis revealed two antioxidant response elements (ARE) in the mouse SRX promoter. Transient transfection studies, using reporter constructs containing the SRX promoter, in NRF2‐/‐, wild‐type, and KEAP1‐/‐ MEF cells demonstrated low, modest and high repor

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