Glutathione peroxidases and redox-regulated transcription factors.
Analysis of the selenoproteome identified five glutathione peroxidases (GPxs) in mammals: cytosolic GPx (cGPx, GPx1), phospholipid hydroperoxide GPx (PHGPX, GPx4), plasma GPx (pGPX, GPx3), gastrointestinal GPx (GI-GPx, GPx2) and, in humans, GPx6, which is restricted to the olfactory system. GPxs reduce hydroperoxides to the corresponding alcohols by means of glutathione (GSH). They have long been considered to only act as antioxidant enzymes. Increasing evidence, however, suggests that nature has not created redundant GPxs just to detoxify hydroperoxides. cGPx clearly acts as an antioxidant, as convincingly demonstrated in GPx1-knockout mice. PHGPx specifically interferes with NF-kappaB activation by interleukin-1, reduces leukotriene and prostanoid biosynthesis, prevents COX-2 expression, and is indispensable for sperm maturation and embryogenesis. GI-GPx, which is not exclusively expressed in the gastrointestinal system, is upregulated in colon and skin cancers and in certain cultured cancer cells. GI-GPx is a target for Nrf2, and thus is part of the adaptive response by itself, while PHGPx might prevent cancer by interfering with inflammatory pathways. In conclusion, cGPx, PHGPx and GI-GPx have distinct roles, particularly in cellular defence mechanisms. Redox sensing and redox regulation of metabolic events have become attractive paradigms to unravel the specific and in part still enigmatic roles of GPxs.
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CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-N GENE-Y GENE-N GENE-N GENE-N GENE-N GENE-Y GENE-N GENE-N GENE-N GENE-N GENE-N GENE-N GENE-N GENE-N GENE-N GENE-N GENE-N GENE-Y GENE-N GENE-N GENE-N GENE-Y GENE-Y GENE-N GENE-N GENE-N GENE-N GENE-Y GENE-N GENE-N GENE-N
alcohols glutathione GSH glutathione leukotriene prostanoid Glutathione GI-GPx Nrf2 cGPx PHGPx GPx1 phospholipid hydroperoxide GPx cGPx PHGPx GI-GPx GPxs PHGPX GPx4 plasma GPx pGPX GPx3 gastrointestinal GPx GI-GPx GPx2 humans, GPx6 GPxs glutathione peroxidases GPxs cGPx GPx1 PHGPx NF-kappaB interleukin-1 GPxs COX-2 GI-GPx cytosolic GPx Glutathione peroxidases