Role of sulfiredoxin as a regulator of peroxiredoxin function and regulation of its expression

Woojin Jeong, Soo Han Bae, Michel B. Toledano, Sue Goo Rhee

Research output: Contribution to journalReview articlepeer-review

98 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)447-456
Number of pages10
JournalFree Radical Biology and Medicine
Volume53
Issue number3
DOIs
StatePublished - 1 Aug 2012

Keywords

  • AP-1
  • Cysteine hyperoxidation
  • Free radicals
  • Lipopolysaccharide
  • Nrf2
  • Peroxiredoxin
  • Sulfiredoxin
  • Toll-like receptor 4

Fingerprint

Dive into the research topics of 'Role of sulfiredoxin as a regulator of peroxiredoxin function and regulation of its expression'. Together they form a unique fingerprint.

Cite this