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Query: UNIPROT:P36969 (phospholipid hydroperoxide glutathione peroxidase)
 344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glutathione peroxidases (GPxs) are a family of enzymes that scavenge peroxides generated in cells. We carried out molecular cloning for cDNAs of four GPx isozymes (GPx-1 through 4) in primate species. The essential residues for the function of these isozymes were well conserved. A phylogenetic tree of GPx isozymes of primates and other mammals showed that GPx-4 diverged first, followed by GPx-3, GPx-2, and GPx-1. Expression of mRNAs for GPx-2 through 4 in various tissues of Japanese monkey was analyzed by Northern blot hybridization. GPx-2 mRNA was detected at 1.7 kb, exclusively in the stomach and small intestine. GPx-3 mRNA was detected at 1.8 kb, intensively in the kidney and adrenal gland, and weakly in the cerebellum, heart, and lung. GPx-4 mRNA was detected at 1.1 kb, very intensively in the testis and weakly in lung, heart, and cerebellum. These results showed that GPx isozymes were expressed under tissue-specific regulations.
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PMID:Structure, gene expression, and evolution of primate glutathione peroxidases. 1596 96

The mRNA levels of three antioxidant genes, Cu/Zn superoxide dismutase (SOD), catalase (CAT) and phospholipid hydroperoxide glutathione peroxidase (GSH-Px), were quantified with real-time qRT-PCR in liver of Atlantic salmon Salmo salar exposed to 80% (normoxia), 105% and 130% O2 saturation for 54 days. The salmon were then translocated and exposed to 90% and 130% O2 saturation for additional 72 days during smoltification. TBARS and vitamin E levels in liver and the levels of oxidized glutathione (GSSG), total glutathione (GSH) and the resulting oxidative stress index (OSI) in blood were quantified as traditional oxidative stress markers. No significant mean normalized expression (MNE) differences of SOD, CAT or GSH-Px were found in liver after hyperoxia exposure at the two sampling times. Significantly decreased OSI was found in smolt exposed to 130% O2 saturation after 126 days (n = 18, P < 0.0001), indicating hyperoxia-induced oxidative stress. No effects were seen on growth, or on the levels of thiobarbituric reactive substances (TBARS) and vitamin E in liver after the exposure experiment. Overall, the mRNA expression of SOD, CAT and GSH-Px in liver related poorly with the hyperoxic exposure regimes, and more knowledge are needed before the expressed levels of these antioxidant genes can be applied as biomarkers of hyperoxia in Atlantic salmon.
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PMID:mRNA expression of antioxidant enzymes (SOD, CAT and GSH-Px) and lipid peroxidative stress in liver of Atlantic salmon (Salmo salar) exposed to hyperoxic water during smoltification. 1610 25

Selenium (Se) is involved in the process of male reproduction. Several studies have been carried out to find the mechanism of Se action through identified selenoproteins. Especially selenoenzyme phospholipid glutathione peroxidase (PHGPx, GPx-4) plays a pivotal role in regulating spermatogenesis. However, the action of selenium is best known as an antioxidant which acts through various selenoproteins viz. glutathione peroxidase, thioredoxin reductase and selenoprotein P. Oxidative stress is currently being considered a leading cause of male infertility. Presently, the involvement of redox active transcription factor, AP1 (Activator protein1) in testicular function was studied. AP1 is redox sensitive and also controls cell proliferation. The effects of Se might be mediated through it. Different Se status - deficient, adequate and excess Se - were generated in male Balb/c mice by feeding yeast based selenium deficient diet and deficient diet supplemented with Se as sodium selenite (0.2 and 1 ppm Se), respectively, for a period of 4 and 8 weeks. Se status was checked by measuring the Se levels and glutathione peroxidase (GSH-Px) activity in testis and liver. The reproductive potential of mice was affected at these changed Se levels. Changes in the activity of superoxide dismutase (SOD), levels of reduced glutathione (GSH) and oxidized glutathione (GSSG) were observed indicating increased oxidative stress at both the levels. Further, changes in the mRNA expression of GSH-Px, gamma-glutamylcysteine synthetase gammaGCS) and Mn superoxide dismutase (MnSOD) were observed. Decrease in cjun and cfos mRNA levels were observed at both the Se status (deficient and excess) which might be responsible for decreased germ cell number, differentiation and reduced fertility observed at the altered Se levels.
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PMID:Role of selenium in regulation of spermatogenesis: involvement of activator protein 1. 1641 Jun 37

The transcript levels of three genes coding for antioxidants, Cu/Zn superoxide dismutase (SOD), catalase and phospholipid hydroperoxide glutathione peroxidase (GSH-Px), and those of two stress proteins, metallothionein (MT) and CYP1A, were examined with real-time quantitative (q) RT-PCR in hepatic tissue of Atlantic cod exposed to 46% (hypoxia), 76% (normoxia) and 145% (hyperoxia) O(2) saturation (tank outlet). To evaluate the oxidative stress state, the levels of total glutathione (tGSH), reduced glutathione (GSH) and oxidized glutathione (GSSG) and subsequently the oxidative stress index (OSI), were determined in the same tissue samples. The transcript level of GSH-Px was significantly upregulated in fish exposed to hyperoxia, and significantly downregulated in fish exposed to hypoxia, compared to the normoxia group. Significant downregulation was also found for SOD and CYP1A transcriptional levels in fish exposed to hypoxia. The transcript levels of catalase and MT did not change in liver of cod exposed to suboptimal oxygen levels. No significant differences were seen between the groups for tGSH, GSH, GSSG or OSI. Prolonged exposure to unfavourable oxygen saturation levels did not alter the OSI, indicating that the antioxidant glutathione system is maintained at an unchanged level in liver of the examined cod.
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PMID:Effects of hypo- and hyperoxia on transcription levels of five stress genes and the glutathione system in liver of Atlantic cod Gadus morhua. 1685 73

A novel cDNA of phospholipid hydroperoxide glutathione peroxidase (PHGPx), which encodes a functional protein capable of complementing the yeast PHGHX-deletion mutant, was recently discovered in radish (Raphanus sativus) and designated as RsPHGPx [Yang X-D, Li W-J, Liu J-Y (2005) Biochim Biophys Acta 1728:199-205]. Sequence alignment suggested that RsPHGPx contains a targeting peptide required for transport to mitochondria, but the experimental evidence for the exact intracellular distribution of RsPHGPx remains to be elucidated. To uncover the cellular localization of plant PHGPx, we first investigated RsPHGPx's intracellular distribution. Western blot analysis of subcellular fractions using the RsPHGPx antiserum clearly indicated the distribution of RsPHGPx in the radish mitochondrial fraction. Furthermore, a construct expressing the RsPHGPx precursor tagged with green fluorescent protein was introduced into tobacco and yeast cells, and the fusion protein was transported into both mitochondria, indicating that RsPHGPx was indeed localized in mitochondria. To explore the biochemical functions of this enzyme, we tested the enzymatic activity of the recombinant RsPHGPx protein. It displayed GSH-dependent peroxidase activity and exhibited the largest affinity to and the highest catalytic efficiency on phosphatidylcholine hydroperoxide, suggesting that phospholipid hydroperoxide is probably the optimum substrate for RsPHGPx. Furthermore, RsPHGPx showed a much higher V (max) value, by two orders of magnitude, than those of all other known plant PHGPxs. Taken together, these results showed evidence for the first time of mitochondrial localization and higher activity of PHGPx in plants and provided a framework for continued studies on the physiological functions of RsPHGPx.
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PMID:A plant mitochondrial phospholipid hydroperoxide glutathione peroxidase: its precise localization and higher enzymatic activity. 1694 66

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

The mechanisms of physiological responses in Atlantic cod, Gadus morhua following vaccination with a heat-killed Vibrio anguillarum were investigated by transcriptome analysis of spleen tissues. Semi-quantitative RT-PCR of several genes involved in immune defense, inflammation, antioxidant defense and glucose transport were determined in vaccinated fish at 1, 3, 7 and 10 days after vaccination (dpv)and compared with sham-injected fish. Transcript levels of the selected genes involved in bacterial defense such as the bactericidal permeability-increasing protein/lipopolysaccharide-binding protein (BPI/LBP), g-type lysozyme and transferrin, were significantly upregulated (P < 0.05) throughout the duration of sampling (1-10 dpv). There was differential expression of the genes involved in antiviral activity, cellular immunity, antioxidant defense and glucose transport, while the pro-inflammatory cytokines remained relatively unchanged in both the vaccinated and sham-vaccinated fish. The expressions of interferon stimulated gene-15 (ISG-15) and interferon regulatory factor-1 (IRF-1), which are involved in viral defense, were significantly enhanced (P < 0.05) after vaccination. Likewise, the transcript levels of the non-specific cytotoxic cell receptor protein-1 (NCCRP-1) and granzyme A/K, which are components of the cell-mediated immunity were upregulated. Among the antioxidants, the transcript levels of catalase and phospholipid hydroperoxide glutathione peroxidase (GSH-Px) significantly increased (P < 0.05) following vaccination, while glucose transporter-4 (GLUT-4) was enhanced among the genes involved in glucose transport. Our results indicate that the spleen of Atlantic cod is able to mount a potent physiological response through enhanced transcription of at least the mentioned genes, upon exposure to a bacterial antigen. These genes work synergistically to protect the fish during subsequent infection.
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PMID:Profiling gene expression in the spleen of Atlantic cod, Gadus morhua upon vaccination with Vibrio anguillarum antigen. 1931 30

The equilibrium of the creation and scavenging of free radicals is mandatory in the spermatozoa to fertilize and initiate a full-term pregnancy. The glutathione (GSH) enzymatic system studies have discovered its relationship with oxidative stress in the ejaculate and new strategies to regulate its activity in the semen could be developed. Intracellular sperm GSH system components are altered in infertile men, and these alterations seem to be linked to sperm morphology. We have been able to correlate embryo morphology on 8 cell embryos with the sperm expression of GPx family members; this relationship appears quite promising for discovery of molecular causes of male infertility. Oxidative stress imbalance potentially leads to damage of the structure of plasma membrane. The freezing and subsequent thawing of sperm is a physically stressful process carried out during routine procedures in assisted reproduction, which results in a highly variable and unpredictable reduction of motile sperm. Subsequently, oxidative status can positively or negatively affect the motility, viability, and fertilizing capacity of thawed sperm. A reserve of glutathione, together with GPx expression, is necessary to eliminate free radicals using GSH or GPx-4 like structural protein and seems to be essential for a good post thaw recovery.
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PMID:The human sperm glutathione system: a key role in male fertility and successful cryopreservation. 1935 30

Kinetics and molecular mechanisms of GPx-type enzymes are reviewed with emphasis on structural features relevant to efficiency and specificity. In Sec-GPxs the reaction takes place at a single redox centre with selenocysteine as redox-active residue (peroxidatic Sec, U(P)). In contrast, most of the non-vertebrate GPx have the U(P) replaced by a cysteine (peroxidatic Cys, C(P)) and work with a second redox centre that contains a resolving cysteine (C(R)). While the former type of enzymes is more or less specific for GSH, the latter are reduced by "redoxins". The common denominator of the GPx family is the first redox centre comprising the (seleno)cysteine, tryptophan, asparagine and glutamine. In this architectural context the rate of hydroperoxide reduction by U(P) or C(P), respectively, is enhanced by several orders of magnitude compared to that of free selenolate or thiolate. Mammalian GPx-1 dominates H(2)O(2) metabolism, whereas the domain of GPx-4 is the reduction of lipid hydroperoxides with important consequences such as counteracting 12/15-lipoxygenase-induced apoptosis and regulation of inflammatory responses. Beyond, the degenerate GSH specificity of GPx-4 allows selenylation and oxidation to disulfides of protein thiols. Heterodimer formation of yeast GPx with a transcription factor is discussed as paradigm of a redox sensing that might also be valid in vertebrates.
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PMID:Catalytic mechanisms and specificities of glutathione peroxidases: variations of a basic scheme. 1937 95

The aim of the study was to characterize the enzymatic and non-enzymatic components comprising the antioxidant system in spermatozoa and individual fractions of dog ejaculate. Ejaculates were collected from six dogs of mixed-breeds. Total protein content, activity of antioxidant enzymes and the content of low-molecular antioxidants, such as L-glutathione (GSH), L-ergothioneine (ERG), L-ascorbic acid and total SH-group, were analyzed in the ejaculated spermatozoa and seminal plasma of the pre-spermatic, spermatic and post-spermatic fractions. The total antioxidant status (TAS) and antiperoxidant activity of the seminal plasma were also determined. The enzymatic antioxidant system of canine spermatozoa is mainly represented by superoxide dismutase (SOD) activity and, to a lesser extent, by glutathione peroxidase (GPx) and phospholipid hydroperoxide glutathione peroxidase (PHGPx) activity. Catalase activity was not detected either in the spermatozoa or in the different ejaculate fractions. GSH and ERG were detected in each fraction. Furthermore, a high level of L-ascorbic acid was observed in fractions of the ejaculate. Proteins and low-molecular weight antioxidants could influence the total antioxidant status and antiperoxidant activity of the seminal plasma. Increased suppressive activity against lipid peroxidation was shown only in the pre-spermatic and post-spermatic fractions. The different fractions of dog ejaculate, which are the main source of enzymatic antioxidants and low-molecular antioxidants, play an important role in protecting spermatozoa against reactive oxygen species.
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PMID:Characteristics of antioxidant system in dog semen. 1945 40


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