title: Regulation of peroxiredoxins by nitric oxide in immunostimulated macrophages.
abstract: 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.
authors.affiliation: Institut de Chimie des Substances Naturelles CNRS, 91190 Gif-sur-Yvette, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Diet
authors.forename: Kahina
authors.initials: K
authors.lastname: Abbas
authors.forename: Cécile
authors.initials: C
authors.lastname: Bouton
authors.forename: Blanche
authors.initials: B
authors.lastname: Guillon
authors.forename: Flora
authors.initials: F
authors.lastname: Tomasello
authors.forename: Simon
authors.initials: S
authors.lastname: Fourquet
authors.forename: Michel B
authors.initials: MB
authors.lastname: Toledano
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Drapier
mesh_terms: 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
chemical_list: D016877:Oxidants; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D054465:Peroxiredoxin VI; D054464:Peroxiredoxins; C489899:Prdx1 protein, mouse; C515983:Prdx6 protein, mouse