RRC ID |
11865
|
著者 |
Abbas K, Breton J, Planson AG, Bouton C, Bignon J, Seguin C, Riquier S, Toledano MB, Drapier JC.
|
タイトル |
Nitric oxide activates an Nrf2/sulfiredoxin antioxidant pathway in macrophages.
|
ジャーナル |
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.
|
巻・号 |
51(1)
|
ページ |
107-14
|
公開日 |
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
|
引用数 |
51
|
WOS 分野
|
ENDOCRINOLOGY & METABOLISM
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
リソース情報 |
実験動物マウス |
RBRC01390 |