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)

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

Gopc (Golgi-associated PDZ- and coiled-coil motif-containing protein)(-/-) mice are infertile, showing globozoospermia, coiled tails, and a stratified mitochondrial sheath. Transmission electron microscope (TEM) images of the spermatozoa were studied quantitatively to analyze disorganization processes during epididymal passage. Factors maintaining straight tail and normal mitochondrial sheath were also studied by TEM and immunofluorescent microscopy. Sperm tails retained a normal appearance in the proximal caput epididymidis. Tail disorganization started between the proximal and the middle caput epididymidis, and the latter is the major site for it. The tail moved up through the defective posterior ring and coiled around the nucleus to various degrees. Tail coiling occurred in the caput epididymidis suggesting it was triggered by cytoplasmic droplet migration. SPATA19/spergen-1, a candidate mitochondrial adhesion protein, remained on the stratified mitochondria, while GPX4/PHGPx, a major element of the mitochondrial capsule, was unevenly distributed on them. From these findings, we speculate GPX4 is necessary to maintain normal sheath structure, and SPATA19 prevents dispersal of mitochondria, resulting in a stratified mitochondrial sheath formation in Gopc(-/-) spermatozoa. The epididymal epithelium was normal in structure and LRP8/apoER2 expression suggesting that tail abnormality is due to intrinsic sperm factors. Three cell structures are discussed as requisite factors for maintaining a straight tail during epididymal maturation: 1) a complete posterior ring to prevent invasion of the tail into the head compartment, 2) stable attachment of the connecting piece to the implantation fossa, and 3) a normal mitochondrial sheath supported by SPATA19 and supplied with sufficient and normally distributed GPX4.
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PMID:Factors maintaining normal sperm tail structure during epididymal maturation studied in Gopc-/- mice. 1736 Sep 59

Selenium, as an integral part of selenoproteins, is essential for mammals. Unequivocal evidence had been provided more than a decade ago when it was proven that mice incapable of producing any of the 24 selenoproteins failed to develop beyond the gastrulation stage (E6.5). Since then, more specific attempts have been made to unmask novel and essential functions of individual selenoproteins in mice. Genetic disruption of glutathione peroxidase 4 (GPx4; also referred to as phospholipid hydroperoxide glutathione peroxidase, PHGPx) in mice showed for the first time that a specific selenoenzyme is in fact required for early embryonic development. Later on, systemic ablation of cytosolic thioredoxin reductase (Txnrd1) or mitochondrial thioredoxin reductase (Txnrd2) yielded embryonic lethal phenotypes. Beside those three, no other selenoproteins have been found being indispensable for murine development so far. This review aims at summarizing mainly the in vivo findings on these important mammalian selenoenzymes, which have not only common attributes of being required for embryogenesis, but that they are also instrumental in the regulation of cellular redox metabolism.
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PMID:Transgenic mouse models for the vital selenoenzymes cytosolic thioredoxin reductase, mitochondrial thioredoxin reductase and glutathione peroxidase 4. 1943 32

Oxidative stress and oxidized dopamine contribute to the degeneration of the nigrostriatal pathway in Parkinson's disease (PD). Selenoproteins are a family of proteins containing the element selenium in the form of the amino acid selenocysteine, and many of these proteins have antioxidant functions. We recently reported changes in expression of the selenoprotein, phospholipid hydroperoxide glutathione peroxidase GPX4 and its co-localization with neuromelanin in PD brain. To further understand the changes in GPX4 in PD, we examine here the expression of the selenium transport protein selenoprotein P (Sepp1) in postmortem Parkinson's brain tissue. Sepp1 in midbrain was expressed in neurons of the substantia nigra (SN), and expression was concentrated within the centers of Lewy bodies, the pathological hallmark of PD. As with GPX4, Sepp1 expression was significantly reduced in SN from PD subjects compared with controls, but increased relative to cell density. In putamen, Sepp1 was found in cell bodies and in dopaminergic axons and terminals, although levels of Sepp1 were not altered in PD subjects compared to controls. Expression levels of Sepp1 and GPX4 correlated strongly in the putamen of control subjects but not in the putamen of PD subjects. These findings indicate a role for Sepp1 in the nigrostriatal pathway, and suggest that local release of Sepp1 in striatum may be important for signaling and/or synthesis of other selenoproteins such as GPX4.
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PMID:Changes in selenoprotein P in substantia nigra and putamen in Parkinson's disease. 2326 26

Selenium deficiency constitutes a risk factor for the incidence and negative course of severe diseases including sepsis, stroke, autoimmune diseases or cancer. In this study, hypoxia is identified as a powerful stimulus to redirect selenoprotein biosynthesis causing reduced selenoprotein P expression and diminished selenium export from hepatocytes in favour of increased biosynthesis of the essential protective intracellular phospholipid hydroperoxide glutathione peroxidase GPX4. Specifically, hypoxia decreases transcript concentrations of central factors controlling selenium and selenocysteine metabolism including selenophosphate synthetase-2, phosphoseryl-tRNA(SerSec) kinase and selenocysteine lyase, which are all proven to be rate-limiting enzymes in selenoprotein biosynthesis. These effects are paralleled by a general decline of selenoprotein expression; however, not all selenoproteins are affected to the same extent by hypoxia, and GPX4 constitutes an exception as its expression becomes slightly increased. Supplemental selenium is able to overcome the hypoxia-dependent down regulation of selenoprotein expression in our cell culture model system, supporting the concept of using selenium as an adjuvant treatment option in severe diseases. Although it remains to be tested whether these effects constitute a hepatocyte-specific response, the selenium-dependent decline of selenoprotein P biosynthesis under hypoxic conditions may explain the progressive selenium deficit developing in severe diseases.
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PMID:Hypoxia reduces and redirects selenoprotein biosynthesis. 2470 Jan 64

Sunflower seedlings subjected to 120 mM NaCl stress exhibit high total peroxidase activity, differential expression of its isoforms and accumulation of lipid hydroperoxides. This coincides with high specific activity of phospholipid hydroperoxide glutathione peroxidase (PHGPX) in the 10,000g supernatant from the homogenates of 2-6 d old seedling cotyledons. An upregulation of PHGPX activity by NaCl is evident from Western blot analysis. Confocal laser scanning microscopic (CLSM) analysis of sections of cotyledons incubated with anti-GPX4 (PHGPX) antibody highlights an enhanced cytosolic accumulation of PHGPX, particularly around the secretory canals. Present work, thus, highlights sensing of NaCl stress in sunflower seedlings in relation with lipid hydroperoxide accumulation and its scavenging through an upregulation of PHGPX activity in the cotyledons.
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PMID:Signaling role of phospholipid hydroperoxide glutathione peroxidase (PHGPX) accompanying sensing of NaCl stress in etiolated sunflower seedling cotyledons. 2551 99

Spontaneous abortion (SA) is the most frequently occurring pregnancy disorder and is a serious threat to women's health. Identifying novel risk factors and the molecular mechanisms underlying SA are important. The present study reported that the RNA expression levels of long non-coding RNA H19 were lower in SA group compared with those in the control group, and the expression of Bax was increased and levels of Bcl-2 and phospholipid hydroperoxide glutathione peroxidase (GPX4) were decreased in SA group at both the mRNA and protein levels. H19 expression was positively correlated with Bcl-2 and GPX4 expression and negatively linked with Bax levels. It was demonstrated that silencing H19 downregulated Bcl-2 and GPX4 expression and upregulated Bax expression at both the mRNA and protein levels in HTR-8/SVneo trophoblast cells. In conclusion, the present findings suggested that H19 has important roles in SA by promoting apoptosis and ferroptosis.
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PMID:Long non-coding RNA H19 regulates Bcl-2, Bax and phospholipid hydroperoxide glutathione peroxidase expression in spontaneous abortion. 3327 71


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