Sulfiredoxin protects mice from lipopolysaccharide-induced endotoxic shock. - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Antioxidants and Redox Signaling Année : 2011

Sulfiredoxin protects mice from lipopolysaccharide-induced endotoxic shock.

Anne-Gaëlle Planson
Gaël Palais
  • Fonction : Auteur
Matthieu Gerard
  • Fonction : Auteur
Linhdavanh Couvelard
  • Fonction : Auteur
Agnès Delaunay
  • Fonction : Auteur
Sylvain Baulande
Michel B Toledano
  • Fonction : Auteur
  • PersonId : 845436

Résumé

Peroxiredoxins constitute a major family of cysteine-based peroxide-scavenging enzymes. They carry an intriguing redox switch by undergoing substrate-mediated inactivation via overoxidation of their catalytic cysteine to the sulfinic acid form that is reverted by reduction catalyzed by the sulfinic acid reductase sulfiredoxin (Srx). The biological significance of such inactivation is not understood, nor is the function of Srx1. To address this question, we generated a mouse line with a null deletion of the Srx1-encoding Srxn1 gene. We show here that Srxn1(-/-) mice are perfectly viable and do not suffer from any apparent defects under laboratory conditions, but have an abnormal response to lipopolysaccharide that manifests by increased mortality during endotoxic shock. Microarray-based mRNA profiles show that although the response of Srxn1(-/-) mice to lipopolysaccharide is typical, spanning all spectrum and all pathways of innate immunity, it is delayed by several hours and remains intense when the response of Srxn1(+/+) mice has already dissipated. These data indicate that Srx1 activity protects mice from the lethality of endotoxic shock, adding this enzyme to other host factors, as NRF2 and peroxiredoxin 2, which by regulating cellular reactive oxygen species levels act as important modifiers in the pathogenesis of sepsis.

Domaines

Chimie organique
Fichier non déposé

Dates et versions

hal-00606130 , version 1 (05-07-2011)

Identifiants

Citer

Anne-Gaëlle Planson, Gaël Palais, Kahina Abbas, Matthieu Gerard, Linhdavanh Couvelard, et al.. Sulfiredoxin protects mice from lipopolysaccharide-induced endotoxic shock.. Antioxidants and Redox Signaling, 2011, 14 (11), pp.2071-80. ⟨10.1089/ars.2010.3552⟩. ⟨hal-00606130⟩
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