RRC ID 11865
Author Abbas K, Breton J, Planson AG, Bouton C, Bignon J, Seguin C, Riquier S, Toledano MB, Drapier JC.
Title Nitric oxide activates an Nrf2/sulfiredoxin antioxidant pathway in macrophages.
Journal Free Radic Biol Med
Abstract Peroxiredoxins (Prx's) are a family of peroxidases that maintain thiol homeostasis by catalyzing the reduction of organic hydroperoxides, H₂O₂, and peroxynitrite. Under conditions of oxidative stress, eukaryotic Prx's can be inactivated by the substrate-dependent oxidation of the catalytic cysteine to sulfinic acid, which may regulate the intracellular messenger function of H₂O₂. A small redox protein, sulfiredoxin (Srx), conserved only in eukaryotes, has been shown to reduce sulfinylated 2-Cys Prx's, adding to the complexity of the H₂O₂ signaling network. In this study, we addressed the regulation of Srx expression in immunostimulated primary macrophages that produce both reactive oxygen species (ROS) and nitric oxide (NO(•)). We present genetic evidence that NO-mediated Srx up-regulation is mediated by the transcription factor nuclear factor erythroid 2-related factor (Nrf2). We also show that the NO(•)/Srx pathway inhibits generation of ROS. These results reveal a link between innate immunity and H₂O₂ signaling. We propose that an NO(•)/Nrf2/Srx pathway participates in the maintenance of redox homeostasis in cytokine-activated macrophages and other inflammatory settings.
Volume 51(1)
Pages 107-14
Published 2011-7-1
DOI 10.1016/j.freeradbiomed.2011.03.039
PII S0891-5849(11)00212-7
PMID 21466852
MeSH Animals Antioxidants / metabolism* Cells, Cultured Hydrogen Peroxide / metabolism Immunity, Innate Macrophages / metabolism Mice Mice, Inbred C57BL Mice, Knockout NF-E2-Related Factor 2 / metabolism* Nitric Oxide / metabolism* Oxidation-Reduction Oxidative Stress Oxidoreductases Acting on Sulfur Group Donors / genetics Oxidoreductases Acting on Sulfur Group Donors / metabolism* Polymerase Chain Reaction Reactive Oxygen Species / metabolism
IF 6.17
Times Cited 51
Mice RBRC01390