Abstract
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.
MeSH terms
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Animals
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Cell Hypoxia
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Cell Line
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Hydrogen Peroxide / pharmacology
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Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
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Macrophages / cytology*
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Macrophages / drug effects
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Macrophages / metabolism*
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Mice
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Nitric Oxide / pharmacology
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Nuclear Proteins
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Oxidation-Reduction / drug effects
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Peroxidases
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Peroxides / metabolism*
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Peroxides / pharmacology
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Peroxiredoxins / metabolism
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Proteins / genetics
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Proteins / metabolism*
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Signal Transduction* / drug effects
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Sulfinic Acids / metabolism
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Transcription, Genetic / drug effects
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Triazenes / pharmacology
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Up-Regulation / drug effects
Substances
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1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene
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Hif1a protein, mouse
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Hypoxia-Inducible Factor 1, alpha Subunit
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Nuclear Proteins
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Peroxides
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Proteins
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Sulfinic Acids
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Triazenes
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Nitric Oxide
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Hydrogen Peroxide
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Peroxidases
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Sesn2 protein, mouse
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Peroxiredoxins