Peroxiredoxins (Prxs) constitute a family of peroxidases in which cysteine serves as the primary site of oxidation during the reduction of peroxides. Members of the 2-Cys Prx subfamily of Prxs (Prx I to IV in mammals) are inactivated via hyperoxidation of the active-site cysteine to sulfinic acid (Cys-SO2H) during catalysis and are reactivated via an ATP-consuming reaction catalyzed by sulfiredoxin (Srx). This reversible hyperoxidation reaction has been proposed to protect H2O2 signaling molecules from premature removal by 2-Cys Prxs or to upregulate the chaperone function of these enzymes. In addition to its sulfinic acid reductase activity, Srx catalyzes the removal of glutathione (deglutathionylation) from modified proteins. The physiological relevance of both the reversible hyperoxidation of 2-Cys Prxs and the deglutathionylation catalyzed by Srx remains unclear. Recent findings have revealed that Srx expression is induced in mammalian cells under a variety of conditions, such as in metabolically stimulated pancreatic β cells, in immunostimulated macrophages, in neuronal cells engaged in synaptic communication, in lung cells exposed to hyperoxia or cigarette smoke, in hepatocytes of ethanol-fed animals, and in several types of cells exposed to chemopreventive agents. Such induction of Srx in mammalian cells is regulated at the transcriptional level, predominantly via activator protein-1 and/or nuclear factor erythroid 2-related factor 2. Srx expression is also regulated at the translational level in Saccharomyces cerevisiae.
|Number of pages||10|
|Journal||Free Radical Biology and Medicine|
|State||Published - 1 Aug 2012|
Bibliographical noteFunding Information:
The work in the authors' laboratory was supported by Bio R&D Program Grants M10642040001-07N4204-00110 (to S.G.R) and M10642040002-07N4204-00210 (to W.J.), Grant 2011-0018055 (to W.J.), and National Core Research Center Program Grant R15-2006-020 (to W.J.) from the National Research Foundation of Korea. M.B.T. is the recipient of grants from the Equipe labellisée Ligue contre le Cancer and Fondation pour la Recherche Médicale programs.
- Cysteine hyperoxidation
- Free radicals
- Toll-like receptor 4