Nitric oxide activates an Nrf2/sulfiredoxin antioxidant pathway in macrophages

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...

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Bibliographic Details
Published in:Free radical biology & medicine 2011-07, Vol.51 (1), p.107-114
Main Authors: Abbas, Kahina, Breton, Jacques, Planson, Anne-Gaelle, Bouton, Cécile, Bignon, Jérome, Seguin, Cendrine, Riquier, Sylvie, Toledano, Michel B., Drapier, Jean-Claude
Format: Article
Language:English
Subjects:
Animals
antioxidants
Antioxidants - metabolism
Cells, Cultured
Chemical Sciences
cysteine
eukaryotic cells
Free radicals
gene expression regulation
homeostasis
hydrogen peroxide
Hydrogen Peroxide - metabolism
hydroperoxides
Immunity, Innate
innate immunity
Macrophage
macrophages
Macrophages - metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
NF-E2-Related Factor 2 - metabolism
Nitric oxide
Nitric Oxide - metabolism
Organic chemistry
oxidation
Oxidation-Reduction
Oxidative Stress
Oxidoreductases Acting on Sulfur Group Donors - genetics
Oxidoreductases Acting on Sulfur Group Donors - metabolism
peroxidases
Peroxiredoxin
Polymerase Chain Reaction
Reactive Oxygen Species - metabolism
Redox signaling
Sulfiredoxin
thiols
transcription factors
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Summary: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.
ISSN:0891-5849
1873-4596
DOI:10.1016/j.freeradbiomed.2011.03.039