UNIPROT:P36969 - FACTA Search

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

Selenium is an essential component in the two antioxidant enzymes glutathione peroxidase (GSH-Px) and phospholipid hydroperoxide glutathione peroxidase (PLGSH-Px). Free oxygen radicals are involved in the inflammatory process seen in rheumatoid arthritis (RA) and are generated mainly through the phagocytic activity of the polymorphonuclear leucocytes. Several experimental studies indicate that selenium is important to the functioning of the immune system and to the inflammatory process. A low selenium status among patients with RA has been reported from areas with both high and low natural selenium intake. The reduction in the serum level is approx. 10%. This reduction is related to the clinical disease activity in arthritis patients in both cross-sectional and longitudinal studies, and selenium concentrations have been found to fluctuate during the disease. Reduced selenium concentrations have been reported in red blood cells, too, and concentrations have been found to be slightly reduced in the polymorphonuclear leucocytes. Studies do not agree on the activity of GSH-Px among RA patients. Thus activity levels have been reported to range from low to high. Those studies that have focused on the subgroup of patients with high persistent disease activity have reported reduced GSH-Px activities in both serum, red blood cells and polymorphonuclear leucocytes. Selenium supplementation using organic selenium compounds in doses of around 250 microgram/day increases the selenium concentration in serum and red blood cells considerably. However, supplementation is not reflected in the selenium level in polymorphonuclear leucocytes from RA patients as opposed to healthy subjects, in whom the level of selenium in polymorphonuclear leucocytes increases. Selenium supplementation increased GSH-Px activity in serum, red blood cells and platelets from RA patients, but in the polymorphonuclear leucocytes the increase was not sufficient to reach the levels of the controls. This apparent lack of de novo synthesis of GSH-Px in polymorphonuclear leucocytes from RA patients may be explained by their inability to increase their selenium content in spite of high levels of available extracellular selenium. this may be in accordance with the lack of anti-arthritic effect of selenium supplementation in controlled clinical studies among RA patients. Several experimental studies have reported inhibition of GSH-Px by antirheumatic drugs, in particular gold. In addition, gold has been found to reduce selenium in rat plasma. These interactions can, however, be modified by increasing the amount of selenium in the feed. Among RA patients there is no clear evidence of an interaction between gold, selenium and GSH-Px.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Selenium and the selenium-dependent glutathione peroxidase in rheumatoid arthritis. 792 58

The involvement of Se enzymes in the protection against the oxidative stress induced by adriamycin (ADR) in rat heart has been studied in animals fed for 10 weeks at three different levels of Se content (low = 0.02 ppm; normal = 0.5 ppm; high = 1.0 ppm) and receiving a weekly injection of 3 mg/kg ADR for 4 weeks. ECG (QaT duration) and contractility of isolated atria were measured. The high-Se diet showed a significant protection on both parameters. To assess the hypothesis that an increase of specific activity of antioxidant Se enzymes may account for the cardioprotective effect of selenium, glutathione peroxidase (GPX), and phospholipid hydroperoxide glutathione peroxidase (PHGPX) were tested. The assays were performed on ventricles isolated from treated rats. At the end of the experimental period, GPX (cytosolic enzyme) did not show any significant difference between controls and ADR-treated at any level of Se content, thus excluding its involvement in the cardioprotection observed in high-Se ADR-treated animals. PHGPX, which is present both in cytosol and in the cell membrane, showed a trend to increase its activity in the presence of ADR treatment only in the membrane fraction; however, the statistical significance was reached only in the low-Se group (+100%). This observation suggests that membrane PHGPX might be involved in the cellular mechanism of adaptation of the heart to the toxic effects of ADR; however, the behavior of these enzymes does not seem to account for the significant protection of selenium supplementation both on ECG and on contractile indices of ADR cardiotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protective effect of dietary selenium supplementation on delayed cardiotoxicity of adriamycin in rat: is PHGPX but not GPX involved? 800 24

Murine leukemia L1210 cells grown for 2-3 weeks in the presence of 1% serum without selenium supplementation [L.Se(-) cells] typically exhibited < 10% of the glutathione peroxidase (GPX) and phospholipid hydroperoxide glutathione peroxidase (PHGPX) activity of selenium-satisfied controls [L.Se(+) cells]. Concomitant with diminished GPX and PHGPX activity was a 1.5- to 2.0-fold increase in catalase (CAT) activity, which reverted to control levels when L.Se(-) cells were given sufficient Se for full expression of selenoperoxidase activity. Selenium manipulation affected total glutathione content similarly, but had no effect on glutathione-S-transferase or superoxide dismutase activity. Long-term growth under Se-deficient conditions resulted in a progressive additional increase in CAT activity, which maximized after ca. 5 months. These cells [referred to as L'.Se(-)] attained CAT activity levels at least 100-times greater than those of Se-supplemented [L'.Se(+)] controls, whereas their glutathione content remained elevated by approximately 70%. Supplying L'.Se(-) cells with Se resulted in a rapid elevation to full GPX activity; however, CAT failed to decline in this case, suggesting that a selection for stable CAT hyperexpressing variants had been accomplished. Quantitative immunoblot analysis indicated that the high CAT activity of L'.Se(-) cells is accounted for by an elevated level of enzyme protein. Induction of CAT and selection for CAT-rich phenotypes, as apparent for Se-starved L1210 cells, was not observed in human K562 counterparts, which lack GPX and express only a low level of PHGPX. L.Se(-) cells were found to be more sensitive to H2O2-induced killing than L.Se(+) controls, whereas L'.Se(-) cells were exceedingly more resistant to H2O2 than L'.Se(+) counterparts. By contrast, L.Se(-) and L'.Se(-) cells were both more sensitive to t-butyl hydroperoxide than Se(+) controls, consistent with CAT being unimportant in the detoxification of this peroxide compared with GPX. This appears to be the first reported evidence for CAT hyperexpression in response to selenium deprivation.
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PMID:Hyperexpression of catalase in selenium-deprived murine L1210 cells. 834 49

We have characterized a new selenium-dependent glutathione peroxidase, GSHPx-GI, by expressing a GSHPx-GI cDNA isolated from human hepatoma HepG2 cells in human mammary carcinoma MCF-7 cells, which have virtually undetectable expression of either the classical cellular enzyme, GSHPx-1, or GSHPx-GI at the protein level. One of the G418-resistant clones, neo-D1, expresses the transfected GSHPx-GI cDNA. This is based on 1) the presence of an additional GSHPx-GI DNA restriction fragment detected by Southern analysis; 2) the presence of a 1.9-kilobase (kb) GSHPx-GI mRNA in addition to the 1.0-kb endogenous mRNA by Northern analysis; and 3) the appearance of a 22-kDa 75Se-labeled protein which is absent in parental MCF-7 cells revealed by SDS-polyacrylamide gel electrophoresis. GSHPx-GI expressed in neo-D1 is a tetrameric protein localized in cytosol. GSHPx-GI does not cross-react with antisera against human GSHPx-1 or human plasma glutathione peroxidase (GSHPx-P). Similar substrate specificities are found for GSHPx-1 and GSHPx-GI; they both catalyze the reduction of H2O2, tert-butyl hydroperoxide, cumene hydroperoxide, and linoleic acid hydroperoxide with glutathione, but not of phosphatidylcholine hydroperoxide. GSHPx-GI mRNA was readily detected in human liver and colon, and occasionally in human breast samples, but not other human tissues including kidney, heart, lung, placenta, or uterus. In rodent tissues, GSHPx-GI mRNA is only detected in the gastrointestinal tract, and not in other tissues including liver. In fact, GSHPx-GI appears to be the major glutathione-dependent peroxidase activity in rodent GI tract. This finding suggests that GSHPx-GI could play a major role in protecting mammals from the toxicity of ingested lipid hydroperoxides. In conclusion, we have demonstrated that GSHPx-GI is the fourth member in the selenium-dependent glutathione peroxidase family, in addition to GSHPx-1, GSHPx-P, and phospholipid hydroperoxide glutathione peroxidase (PHGPX).
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PMID:Expression, characterization, and tissue distribution of a new cellular selenium-dependent glutathione peroxidase, GSHPx-GI. 842 33

Evidence that rat liver microsomal glutathione transferase is responsible for the glutathione-dependent inhibition of lipid peroxidation in liver microsomes has been obtained. Activation of the microsomal glutathione transferase in microsomes by cystamine renders this organelle even more resistant to lipid peroxidation in the presence of glutathione compared with untreated microsomes. Upon examining the effect of seven glutathione analogues on lipid peroxidation, it was found that only those that serve as good substrates for the microsomal glutathione transferase (Glutaryl-L-Cys-Gly and alpha-L-Glu-L-Cys-Gly) can inhibit lipid peroxidation. The lack of inhibition by the other five analogues (alpha-D-Glu-L-Cys-Gly, gamma-D-Glu-L-Cys-Gly, beta-L-Asp-L-Cys-Gly, alpha-L-Asp-L-Cys-Gly and alpha-D-Asp-L-Cys-Gly) shows the specificity of the protection and rules out any non-enzymic component. Inhibitors of selenium-dependent glutathione peroxidase (mercaptosuccinate at 50 microM) and phospholipid hydroperoxide glutathione peroxidase (iodoacetate, 1 mM + glutathione, 0.5 mM) do not inhibit the glutathione-dependent protection of rat liver microsomes against lipid peroxidation. Purified microsomal glutathione transferase, NADPH-cytochrome P450 reductase and cytochrome P450 were reconstituted in microsomal phospholipid vesicles by cholate dialysis. The resulting membranes contained functional enzymes and did display enzymic lipid peroxidation induced by 75 microM NADPH and 10 microM Fe-EDTA (2:1). This model system was used to investigate whether microsomal glutathione transferase could inhibit lipid peroxidation in a glutathione-dependent manner. The results show that 5 mM glutathione did inhibit lipid peroxidation when functional microsomal glutathione transferase was included. This was not the case when the enzyme had been pre-inactivated with diethylpyrocarbonate. Furthermore, the protective effect of glutathione could be partly reversed by an inhibitor (100 microM bromosulphophtalein) of the enzyme. Apparently, rat liver microsomal glutathione transferase has the capacity to inhibit lipid peroxidation in a reconstituted system.
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PMID:Evidence that rat liver microsomal glutathione transferase is responsible for glutathione-dependent protection against lipid peroxidation. 848 4

Selenium depletion of H4 hepatoma cells reduced cytosolic glutathione peroxidase (cGSH-Px) mRNA abundance but had no effect on phospholipid hydroperoxide glutathione peroxidase (PHGSH-Px) mRNA abundance. Actinomycin D chase experiments showed that selenium depletion had no effect on the stability of PHGSH-Px mRNA but decreased the stability of cGSH-Px mRNA. In Se-replete cells puromycin decreased the stability of both cGSH-Px and PHGSH-Px mRNAs. The results suggest that when selenium supply is limiting PHGSH-Px mRNA translation is maintained more than that of cGSH-Px mRNA, and thus more cGSH-Px mRNA is released from polysomes and degraded.
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PMID:Selective control of cytosolic glutathione peroxidase and phospholipid hydroperoxide glutathione peroxidase mRNA stability by selenium supply. 867 40

The 100000Xg supernatant parasite platyhelminth Schistosoma mansoni exhibits a glutathione peroxidase activity with the substrate phosphatidylcholine hydroperoxide. Purification yielded a protein of 20 kDa molecular mass both on gel filtration column chromatography and SDS/PAGE, thus suggesting that S. mansoni expresses a protein similar to the mammalian selenoenzynic phospholipid-hydroperoxide glutathione peroxidase. Kinetic analysis and substrate specificity corroborated this assumption, the second-order rate constants for the oxidation of the ground-state enzyme (k+1) being higher with phosphatidylcholine hydroperoxide than with other peroxide substrates, such as cumene liydroperoxide or H2O2, and quantitatively similar to those of mammalian phospholipid-hydroperoxide glutathione peroxidase. Partial sequencing of the protein and selenium measurement by neutron activation analysis established that the purified peroxidase corresponded to the product of the S. mansoni gene previously reported and supposed to encode a selenium-containing glutathione peroxidase [Roche, C., Williams, D. L., Khalife, J., LePresle, T., Capron, A. & Pierce, R. J. (1994) Cloning and characterization of gene encoding Schistosoma mansoni glutathione peroxidase, Gene 138, 149 - 152]. S. mansoni thus contains a scienoperoxidase sharing molecular mass, catalytic efficiency and substrate specificity with phospholipid-hydroperoxide glutathione peroxidase, dismantling the concept that those enzymes are unique to vertebrate organisms.
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PMID:A selenium-containing phospholipid-hydroperoxide glutathione peroxidase in Schistosoma mansoni. 870 88

Selenium repletion of selenium-deficient rats with 20 micrograms selenium / kg body weight as Na2SeO3 was used as a model to investigate the mechanisms that control the distribution of the trace element to specific selenoproteins in liver and thyroid. Cytosolic glutathione peroxidase (cGSHPx), phospholipid hydroperoxide glutathione peroxidase (PHGSHPx), and iodothyronine 5'-deiodinase (IDI) activities were all transiently increased in liver 16 to 32 h after ip injection with selenium. However, only cGSHPx and PHGSHPx activities increased in the thyroid where IDI activity was already increased by selenium deficiency. These responses were owing to synthesis of the seleoproteins on newly synthesised and/or existing mRNAs. The selenoprotein mRNAs in the thyroid gland were increased two- and threefold after the transitory increases in selenoprotein activity. In contrast, there were parallel changes in selenoprotein mRNAs and enzyme activities in the liver, with no prolonged rises in mRNA levels. The organ differences suggest that increased thryotrophin (TSH) concentrations, which are known to induce thyrodial IDI and mRNA, may control the mRNAs for all the thyroidal selenoproteins investigated and be a major mechanism for the preservation of thyroidal selenoproteins when selenium supplies are limited.
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PMID:Selenoprotein gene expression during selenium-repletion of selenium-deficient rats. 872 69

The stimulation of thyroid hormone synthesis in iodine deficiency may increase the requirement for the selenoproteins which are involved in thyroid hormone synthesis in the thyroid gland. Selenoenzyme activity and expression were investigated in the thyroid and liver of second generation selenium-and/or iodine-deficient rats. Selenium deficiency caused substantial decreases in hepatic selenium-containing type I iodothyronine deiodinase (ID-I) and cytosolic glutathione peroxidase (cGSHPx) activities and mRNA abundances, but phospholipid hydroperoxide glutathione peroxidase (phGSHPx) activity was only 55% of selenium-supplemented control levels, despite the absence of change in its mRNA abundance. Selenoenzyme mRNA concentrations were maintained at control levels in thyroid glands from the selenium-deficient rat pups. Despite this, a differential effect was observed in selenoenzyme activities: ID-I activity was decreased to 61%, cGSHPx activity to 45% and phGSHPx to 29% of that in selenium-adequate controls. In iodine-deficient thyroid glands, mRNA levels were increased 2.2, 5.0 and 2.8 times for ID-I, cGSHPx and phGSHPx respectively. ID-I and cGSHPx enzyme activities were also increased but the activity of phGSHPx was decreased despite the high mRNA abundance. Thyroid selenoprotein mRNA levels were also increased in combined selenium and iodine deficiency but again there were differential effects on enzyme activities, with ID-I activity increased, cGSHPx unchanged and phGSHPx decreased. Thus, iodine deficiency may produce an oxidant stress on the thyroid gland, increasing the requirement for selenium to maintain selenoenzyme activity. When dietary supplies of selenium are limiting, thyroid selenoprotein mRNA levels are increased to compensate for overall lack of the micronutrient. Furthermore, there is a preferential supply of available selenium to ID-I and cGSHPx to allow maintenance of thyroid function.
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PMID:Selenoenzyme expression in thyroid and liver of second generation selenium- and iodine-deficient rats. 878 84

Commercially available calf serum did not supply the cultured murine fibroblast cell line L929 with amounts of selenium and alpha-tocopherol sufficient to protect against peroxide damage. Supplementation of the culture medium with 30 microM alpha-tocopherol or 50 nM sodium selenite led to a substantial increase of cellular alpha-tocopherol concentrations from 18 +/- 3.0 to 3179 +/- 93.0 pmol/10(6) cells or cellular selenium concentrations from 0.17 +/- 0.02 to 1.75 +/- 0.16 ng/10(6) cells, respectively. L929 fibroblasts grown in selenite-containing medium also had markedly raised activities of both cytosolic glutathione peroxidase (from 11 +/- 0.9 to 67.2 +/- 4.2 mU/10(7) cells) and phospholipid hydroperoxide glutathione peroxidase (from 0.2 to 9.5 +/- 0.9 mU/10(7)cells). Supplementation with alpha-tocopherol inhibited single-strand breaks induced by low concentrations of H2O2 only, whereas an adequate selenium supply almost completely inhibited single-strand breaks induced by up to 30 microM H2O2 and also significantly reduced H2O2-induced cell death. An inadequate selenium supply and corresponding increase of GPx activity upon selenite supplementation was also observed with other cell lines, for instance, D10N, ECV-304, HepG2, and THP-1. Our data strengthen the relevance of standardized and adequate supplementation of tissue culture media with antioxidants to improve viability and genetic stability of cultured cells in general and in particular, if they are oxidatively challenged.
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PMID:Conventional cell culture media do not adequately supply cells with antioxidants and thus facilitate peroxide-induced genotoxicity. 885 40

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