Role of sestrin2 in peroxide signaling in macrophages.
Reactive oxygen species not only serve as signaling molecules, they also contribute to oxidative stress and cell damage. The thioredoxin and glutaredoxin systems form along with peroxiredoxins a precisely regulated defense system to maintain the cellular redox homeostasis. There is evidence that nitric oxide (NO) protects cells from oxidative stress by preventing inactivation of peroxiredoxins by sulfinylation. Here we demonstrate that NO and hypoxia upregulate Sestrin2 by HIF-1-dependent and additional mechanisms and that Sestrin2 contributes to preventing peroxiredoxins from sulfinylation. We conclude that Sestrin2 plays a role in peroxide defense as a reductase for peroxiredoxins.
Essler
Silke
S
Goethe-University Frankfurt, Faculty of Medicine, Biochemistry I, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
Dehne
Nathalie
N
Brüne
Bernhard
B
D000818:Animals; D015687:Cell Hypoxia; D002460:Cell Line; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009569:Nitric Oxide / Q000494:pharmacology; D009687:Nuclear Proteins; D010084:Oxidation-Reduction / Q000187:drug effects; D010544:Peroxidases; D010545:Peroxides / Q000378:metabolism* / Q000494:pharmacology; D054464:Peroxiredoxins / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013441:Sulfinic Acids / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014226:Triazenes / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects; D000084622:Sestrins
D006861:Hydrogen Peroxide; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009569:Nitric Oxide; D009687:Nuclear Proteins; D010544:Peroxidases; D010545:Peroxides; D054464:Peroxiredoxins; D011506:Proteins; D013441:Sulfinic Acids; D014226:Triazenes; C105351:1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene; C497443:Hif1a protein, mouse; C529380:Sesn2 protein, mouse; D000084622:Sestrins