Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P36969 (phospholipid hydroperoxide glutathione peroxidase)
 344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxidative processes are considered to play a crucial role in the induction of cell adhesion molecules, a key event in inflammatory processes. We recently reported on an unexpected unidirectional effect of an overexpressed antioxidant [phospholipid hydroperoxide glutathione peroxidase (PHGPx)] and an oxidant [15-lipoxygenase (15-LOX)] enzyme on the basal and interleukin-1 induced vascular cell adhesion molecule-1 (VCAM-1) expression in vascular smooth muscle cells (SMC). Both enzymes inhibited VCAM-1 expression and reduced the cellular protein thiol content, thus, both exerting an oxidant effect. We now investigated whether transcription factors known to be regulated by oxidation, i.e., the nuclear factor-kappaB and the Keap1/Nrf2 system, were affected in our set of cells: SMC, SMC(PHGPx), and SMC(LOX), as well as ECV and ECV(PHGPx). PHGPx and 15-LOX inhibited nuclear factor-kappaB activation most efficiently at a step downstream of DNA binding, which explains their inhibitory effect on VCAM-1 expression. Both enzymes up-regulated endogenous heme oxygenase-1 most probably via activation of Nrf2. Transfected Nrf2 strongly inhibited VCAM-1 promoter activity, which could be reversed by cotransfection with Keap1. The key player in this complex cross-talk obviously is heme oxygenase-1, which is known to be induced by oxidant-activated Nrf2. The moderate oxidative stress initiated by enhanced PHGPx or 15-LOX activity appears to induce a defense system that diminishes the response to further proinflammatory stimuli.
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PMID:NF-kappaB, Nrf2, and HO-1 interplay in redox-regulated VCAM-1 expression. 1599 44

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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PMID:Glutathione peroxidases and redox-regulated transcription factors. 1708 Nov 3