Regulation of peroxiredoxins by nitric oxide in immunostimulated macrophages.
Reactive oxygen species and nitric oxide (NO) are capable of both mediating redox-sensitive signal transduction and eliciting cell injury. The interplay between these messengers is quite complex, and intersection of their signaling pathways as well as regulation of their fluxes requires tight control. In this regard, peroxiredoxins (Prxs), a recently identified family of six thiol peroxidases, are central because they reduce H2O2, organic peroxides, and peroxynitrite. Here we provide evidence that endogenously produced NO participates in protection of murine primary macrophages against oxidative and nitrosative stress by inducing Prx I and VI expression at mRNA and protein levels. We also show that NO prevented the sulfinylation-dependent inactivation of 2-Cys Prxs, a reversible overoxidation that controls H2O2 signaling. In addition, studies using macrophages from sulfiredoxin (Srx)-deficient mice indicated that regeneration of 2-Cys Prxs to the active form was dependent on Srx. Last, we show that NO increased Srx expression and hastened Srx-dependent recovery of 2-Cys Prxs. We therefore propose that modulation by NO of Prx expression and redox state, as well as up-regulation of Srx expression, constitutes a novel pathway that contributes to antioxidant response and control of H2O2-mediated signal transduction in mammals.
Diet
Alexandre
A
Institut de Chimie des Substances Naturelles CNRS, 91190 Gif-sur-Yvette, France.
Abbas
Kahina
K
Bouton
Cécile
C
Guillon
Blanche
B
Tomasello
Flora
F
Fourquet
Simon
S
Toledano
Michel B
MB
Drapier
Jean-Claude
JC
D000818:Animals; D002460:Cell Line; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000201:enzymology* / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000276:immunology / Q000378:metabolism*; D016877:Oxidants / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D054465:Peroxiredoxin VI / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D054464:Peroxiredoxins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D030421:Peroxynitrous Acid / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D016877:Oxidants; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D054465:Peroxiredoxin VI; D054464:Peroxiredoxins; C489899:Prdx1 protein, mouse; C515983:Prdx6 protein, mouse