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Sulfiredoxin is Regulated by NRF2 During Oxidative Stress in Lungs
Author(s) -
Ling Guoyu,
Sussan Thomas E,
Thimmulappa Rajesh K,
Biswal Shyam
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1122.17
Subject(s) - oxidative stress , keap1 , microbiology and biotechnology , transcription factor , oxidative phosphorylation , chromatin immunoprecipitation , transfection , transcriptional regulation , gene silencing , chemistry , biology , reactive oxygen species , gene expression , promoter , biochemistry , gene
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 reporter activity, respectively, suggesting NRF2‐dependent transcriptional regulation. Chromatin immunoprecipitation assays revealed binding of NRF2 to the ARE element upon hydrogen peroxide treatment. Taken together, our data demonstrates that NRF2 regulates basal and inducible expression of SRX in response to oxidative stress, which may have an important role in cell signaling and protection.