Role of sulfiredoxin as a regulator of peroxiredoxin function and regulation of its expression.
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-SO(2)H) during catalysis and are reactivated via an ATP-consuming reaction catalyzed by sulfiredoxin (Srx). This reversible hyperoxidation reaction has been proposed to protect H(2)O(2) 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.
Department of Life Science, Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea. jeongw@ewha.ac.kr
Woojin
W
Jeong
Soo Han
SH
Bae
Michel B
MB
Toledano
Sue Goo
SG
Rhee
D000818:Animals; D001483:Base Sequence; D005786:Gene Expression Regulation; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011401:Promoter Regions, Genetic; D018808:Transcription Factor AP-1 / Q000378:metabolism
D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D018808:Transcription Factor AP-1; D054464:Peroxiredoxins; D050862:Oxidoreductases Acting on Sulfur Group Donors; C504024:SRXN1 protein, human; D005978:Glutathione