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

We have previously reported that Saccharomyces cerevisiae has three glutathione peroxidase homologues (GPX1, GPX2, and GPX3) (Inoue, Y., Matsuda, T., Sugiyama, K., Izawa, S., and Kimura, A. (1999) J. Biol. Chem. 274, 27002-27009). Of these, the GPX2 gene product (Gpx2) shows the greatest similarity to phospholipid hydroperoxide glutathione peroxidase. Here we show that GPX2 encodes an atypical 2-Cys peroxiredoxin which uses thioredoxin as an electron donor. Gpx2 was essentially in a reduced form even in mutants defective in glutathione reductase or glutaredoxin under oxidative stressed conditions. On the other hand, Gpx2 was partially oxidized in a mutant defective in cytosolic thioredoxin (trx1Deltatrx2Delta) under non-stressed conditions and completely oxidized in tert-butyl hydroperoxide-treated cells of trx1Deltatrx2Delta and thioredoxin reductase-deficient mutant cells. Alanine scanning of cysteine residues of Gpx2 revealed that an intramolecular disulfide bond was formed between Cys37 and Cys83 in vivo. Gpx2 was purified to determine whether it functions as a peroxidase that uses thioredoxin as an electron donor in vitro. Gpx2 reduced H2O2 and tert-butyl hydroperoxide in the presence of thioredoxin, thioredoxin reductase, and NADPH (for H2O2, Km= 20 microm, kcat = 9.57 x 10(2) s(-1); for tert-butyl hydroperoxide, Km= 62.5 microm, kcat = 3.68 x 10(2) s(-1)); however, it showed remarkably less activity toward these peroxides in the presence of glutathione, glutathione reductase, and NADPH. The sensitivity of yeast cells to tert-butyl hydroperoxide was found to be exacerbated by the co-existence of Ca2+, a tendency that was most obvious in gpx2Delta cells. Although the redox state of Gpx2 was not affected by Ca2+, the Gpx2 level was markedly increased in the presence of both tert-butyl hydroperoxide and Ca2+. Gpx2 is likely to play an important role in the protection of cells from oxidative stress in the presence of Ca2+.
 ...
PMID:GPX2, encoding a phospholipid hydroperoxide glutathione peroxidase homologue, codes for an atypical 2-Cys peroxiredoxin in Saccharomyces cerevisiae. 1625 Nov 89

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.
 ...
PMID:Role of selenium in regulation of spermatogenesis: involvement of activator protein 1. 1641 Jun 37

In the sperm nuclei, of mammalian species selenium has been found only in the form of sperm nuclei glutathione peroxidase (snGPx) where it is most likely bound to the chromatin of spermatozoa. Over 80% of selenium in sperm is bound to the selenoprotein phospholipid hydroperoxide glutathione peroxidase (PHGPx) in the midpiece of rat sperm. Zinc in sperm is mainly contained in the outer dense fiber (ODF) proteins of the flagella of mammalian spermatozoa. In the sperm nuclei, zinc is predominately located in the chromatin to the protamine proteins. In order to investigate if the insertion of zinc and selenium in sperm chromatin is regulated, the element concentrations were determined in equine spermatozoa and purified sperm nuclei. We found a significant positive correlation between the selenium concentration in equine spermatozoa and sperm nuclei. The same finding was obtained for the zinc concentration in spermatozoa and sperm nuclei. The results assume that the distribution of selenium and zinc in spermatozoa is regulated by cell signaling pathways and in this way determining the selenium and zinc amount in the chromatin of spermatozoa.
 ...
PMID:Is the distribution of selenium and zinc in the sublocations of spermatozoa regulated? 1740 33

In the present study we investigated promoter regions of the PHGPx [phospholipid hydroperoxide GPx (glutathione peroxidase)] gene and transcription factors involved in TNFalpha (tumour necrosis factor alpha)-induced up-regulation of PHGPx in non-differentiated HL60 cells. Non-differentiated HL60 cells displayed up-regulation of non-mitochondrial and mitochondrial PHGPx mRNA in response to TNFalpha stimulation. The promoter activity was up-regulated by TNFalpha stimulation in cells transfected with a luciferase reporter vector encoding the region from -282 to -123 of the human PHGPx gene compared with the non-stimulated control. The up-regulated promoter activity was effectively abrogated by a mutation in the C/EBP (CCAAT/enhancer-binding protein)-binding sequence in this region. ChIP (chromatin immunoprecipitation) assays demonstrated that C/EBPepsilon bound to the -247 to -34 region in HL60 cells, but C/EBPalpha, beta, gamma and delta did not. The binding of C/EBPepsilon to the promoter region was increased in HL60 cells stimulated with TNFalpha compared with that of the non-stimulated control. An increased binding of nuclear protein to the C/EBP-binding sequence was observed by EMSA (electrophoretic mobility-shift assay) in cells stimulated with TNFalpha, and it was inhibited by pre-treatment with an anti-C/EBPepsilon antibody, but not with other antibodies. The C/EBPepsilon mRNA was expressed in PMNs (polymorphonuclear cells), non-differentiated HL60 cells and neutrophil-like differentiated HL60 cells displaying TNFalpha-induced up-regulation of PHGPx mRNA, but not in macrophage-like differentiated HL60 cells, HEK-293 cells (human embryonic kidney-293 cells) and other cell lines exhibiting no up-regulation. The up-regulation of PHGPx mRNA, however, was detected in HEK-293 cells overexpressing C/EBPepsilon as a result of TNFalpha stimulation. These results indicate that C/EBPepsilon is a critical transcription factor in TNFalpha-induced up-regulation of PHGPx expression.
 ...
PMID:Identification of a responsible promoter region and a key transcription factor, CCAAT/enhancer-binding protein epsilon, for up-regulation of PHGPx in HL60 cells stimulated with TNF alpha. 1768 22

The selenoenzyme sperm nuclei glutathione peroxidase (snGPx), also called the nuclear form of phospholipid hydroperoxide glutathione peroxidase (n-PHGPx), was found to be involved in the stabilization of condensed sperm chromatin, most likely by thiol to disulfide oxidation of the cysteine residues of the mammalian protamines, small nuclear basic proteins in the nuclei of sperm cells. By applying Acidic Urea-PAGE in combination with SDS-PAGE, snGPx with an apparent molecular mass of 34 kDa and a 24-kDa protein were purified from rat sperm nuclei. The 24-kDa protein was identified by means of mass spectrometry as a truncated form of snGPx produced by cleavage at the N-terminal end. After defined processing of spermatozoa and detergent treatment of the sperm nuclei fraction, snGPx and its truncated form were shown to be the only selenoproteins present in mature mammalian sperm nuclei. Both forms were found in mature rat and horse sperm nuclei but in man only snGPx was detected. In trout and chicken, species with sperm cells which likewise undergo chromatin condensation but do not contain cysteine in their protamines, the snGPx proteins were missing. This can be taken as an indirect proof of the function of snGPx to act as protamine cysteine thiol peroxidase in the mammalian species with cysteine-containing protamines.
 ...
PMID:Sperm nuclei glutathione peroxidases and their occurrence in animal species with cysteine-containing protamines. 1771 75

The redox enzyme phospholipid hydroperoxide glutathione peroxidase (PHGPx) has emerged as one of the most significant selenoenzymes in mammals, corroborated by early embryonic lethality of PHGPx null mice. PHGPx is one of five selenium-dependent glutathione peroxidases and the second glutathione peroxidase to be discovered in 1982. PHGPx has a particular position within this family owing to its peculiar structural and catalytic properties, its multifaceted roles during male gametogenesis, and its necessity for early mouse development. Interestingly, mice devoid of endogenous glutathione die at the same embryonic stage as PHGPx-deficient mice compatible with the hypothesis that a similar phenotype of embryonic lethality may be provoked by PHGPx deficiency and lack of its reducing substrate glutathione. Various gain- and loss-of-function approaches in mice have provided some insights into the physiological functions of PHGPx. These include a protective role for PHGPx in response to irradiation, increased resistance of transgenic PHGPx mice to toxin-induced liver damage, a putative role in various steps of embryogenesis, and a contribution to sperm chromatin condensation. The expression of three forms of PHGPx and early embryonic lethality call for more specific studies, such as tissue-specific disruption of PHGPx, to precisely understand the contribution of PHGPx to mammalian physiology and under pathological conditions.
 ...
PMID:Physiological role of phospholipid hydroperoxide glutathione peroxidase in mammals. 1793 15

Human selenium (Se) requirements are currently based on biochemical markers of Se status. In rats, tissue glutathione peroxidase-1 (Gpx1) mRNA levels can be used effectively to determine Se requirements; blood Gpx1 mRNA levels decrease in Se-deficient rats, so molecular biology-based markers have potential for human nutrition assessment. To study the efficacy of molecular biology markers for assessing Se status in humans, we conducted a longitudinal study on 39 subjects (age 45 +/- 11) in Reading, UK. Diet diaries (5 day) and blood were obtained from each subject at 2, 8, 17 and 23 weeks, and plasma Se, glutathione peroxidase (Gpx3) enzyme activity, and selenoprotein mRNA levels were determined. There were no significant longitudinal effects on Se biomarkers. Se intake averaged 48 +/- 14 microg/d. Plasma Se concentrations averaged 1.13 +/- 0.16 micromol/l. Plasma Se v. energy-corrected Se intake (ng Se/kJ/d) was significantly correlated, but neither Gpx3 activity v. Se intake (ng Se/kJ/d) nor Gpx3 activity v. plasma Se was significantly correlated. Collectively, this indicates that subjects were on the plateaus of the response curves. Selenoprotein mRNAs were quantitated in total RNA isolated from whole blood, but mRNA levels for Gpx1, selenoprotein H, and selenoprotein W (all highly regulated by Se in rodents), as well selenoprotein P, Gpx3, and phospholipid hydroperoxide glutathione peroxidase were also not significantly correlated with plasma Se. Thus selenoprotein molecular biomarkers, as well as traditional biochemical markers, are unable to further distinguish differences in Se status in these Se replete subjects. The efficacy of molecular biomarkers to detect Se deficiency needs to be tested in Se-deficient populations.
 ...
PMID:Longitudinal selenium status in healthy British adults: assessment using biochemical and molecular biomarkers. 1859 87

Prenatal exposure to alcohol promotes the level of reactive oxygen species within embryos and results in developmental disorders. In this study, we investigated the effect of capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide), the major pungent ingredient in red peppers, on ethanol-induced teratogenicity in mouse embryos (embryonic days 8.5-10.5). In response to ethanol administration (1.0 microl/ml), developmental parameters such as yolk sac circulation, allantois, heart, hindbrain, midbrain, forebrain, otic and optic systems, branchial bar, olfactory system, forelimb, hindlimb, and somites decreased significantly in comparison with those of control group (p<0.05). However, the concurrent administration of capsaicin (1 x 10(-8) microg/ml or 1 x 10(-7) microg/ml) and ethanol significantly ameliorated most of the morphological scores excepting yolk sac circulation and hindlimb scores (p<0.05). Furthermore, the levels of superoxide dismutase activity and cytoplasmic glutathione peroxidase and phospholipid hydroperoxide glutathione peroxidase mRNAs in the ethanol-treated embryos recovered to the levels observed in control embryos by capsaicin co-administration. These results indicate that capsaicin has a protective effect against ethanol-induced teratogenicity via an antioxidative activity.
 ...
PMID:Capsaicin prevents ethanol-induced teratogenicity in cultured mouse whole embryos. 1892

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.
 ...
PMID:Characteristics of antioxidant system in dog semen. 1945 40

The essential trace element selenium and polyunsaturated fatty acids (PUFA) have been used for the prevention of cancer. Both nutrients enhance the apoptosis of malignant cells and provide health benefits. However, an increased dietary intake of PUFA augments the susceptibility of lipid peroxidation and oxidative damage in many cells. So far, relatively few data are available about the interaction of selenium and PUFA in testis and thus a possible effect of both dietary components on the prevention of testicular cancer or on the apoptosis of testicular germ cells. Male germ cells in the rat contain most of the testicular phospholipid hydroperoxide glutathione peroxidase (PHGPx), mainly as the mitochondrial isoform of this selenoprotein (m-PHGPx). An experiment was therefore carried out to determine the action of fish oil, a nutrient rich in PUFA, on the testicular expression of PHGPx. Because the PHGPx formation remains nearly unchanged in the animals fed the PUFA-enriched diet, we conclude that no apoptosis of testicular germ cells is induced by an increased intake of this nutrient. The intake of fish oil in the selenium-deficient animal led to a markedly altered formation of several selenium-containing proteins, including sperm nuclei glutathione peroxidase (snGPx), also designated as the nuclear form of PHGPx (n-PHGPx), and a 10-kDa selenium-containing protein.
 ...
PMID:Studies with regard to the apoptosis of testicular germ cells in rats fed a diet enriched with polyunsaturated Fatty acids. 1972 78


<< Previous 1 2 3 4 5 6 7 8 9 10