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)

Human plasma glutathione peroxidase was purified to homogeneity and partially sequenced. Overlapping peptide fragments from three endopeptidase digests permitted the determination of one sequence of 32 contiguous amino acids and one sequence of 23 contiguous amino acids. Five additional unique peptide sequences without obvious overlaps were obtained. The sequence of 32 amino acid residues aligns with positions 82-113 of human cytosolic glutathione peroxidase with nine mismatches without gaps or insertions. The sequence of 23 amino acid residues aligns with positions 157-178 with six mismatches and an insertion of one residue. Three additional peptide sequences with no obvious sequence homology to glutathione peroxidase can be aligned based on the sequence of a cDNA clone encoding plasma glutathione peroxidase that was isolated from a human placental library. The plasma enzyme is a homotetramer composed of 21-kDa subunits which cannot reduce phospholipid hydroperoxides. These results indicate that the plasma glutathione peroxidase is distinct from both the classical cytosolic enzyme and the monomeric phospholipid hydroperoxide glutathione peroxidase. Only a negligible amount of glutathione peroxidase activity was detected in bile, indicating that the liver exports plasma glutathione peroxidase exclusively to the circulation.
 ...
PMID:Characterization and partial amino acid sequence of human plasma glutathione peroxidase. 189 60

We studied enzyme kinetics parameters of plasma glutathione peroxidase (GSHPx-P) and the major cellular enzyme, GSHPx-1, for the substrates, H2O2, linoleic acid hydroperoxide (LinOOH), and glutathione (GSH). The major objectives were to determine whether the relatively slow GSHPx-P enzyme had a lower reactivity with hydroperoxides or with GSH and to identify favored hydroperoxide substrates. The rate constants describing the reactivity of human GSHPx-P and human GSHPx-1 with LinOOH and H2O2 are in the same range; GSHPx-P is more reactive with LinOOH and GSHPx-1 is more reactive with H2O2. GSHPx-P also has a low level of reducing activity toward cholesterol 7 alpha-OOH and no detectable activity with the 5 alpha-OOH isomer in contrast to phospholipid hydroperoxide glutathione peroxidase (PHGPx) which readily reduced both isomers. GSHPx-P catalytic activity toward phospholipid hydroperoxides is demonstrable in the absence of detergents, enhanced at low concentrations by deoxycholate, and strongly inhibited by Triton X-100 and incorporation into liposomes. These properties are the opposite of PHGPx. These results suggest that GSHPx-P largely lacks the membrane interfacial properties of PHGPx. GSHPx-P exhibits a smaller GSH rate constant than GSHPx-1. This property partially explains the slower turnover of GSHPx-P with several hydroperoxide substrates; the low reactivity with GSH is not consistent with efficient GSHPx function in the bulk plasma volume. GSHPx-P kinetic properties suggest that it would function best as a free fatty acid hydroperoxidase in GSH-rich microenvironments. Minimally, the secretion of reduced enzyme would permit it to scavenge free fatty acid hydroperoxides.
 ...
PMID:Reactivity of plasma glutathione peroxidase with hydroperoxide substrates and glutathione. 823 61

cDNA probes of human glutathione peroxidase (GSHPx) genes, including the classic GPX1 (GSHPx-1), the newly characterized GPX2 (GSHPx-GI), the plasma enzyme GPX3 (GSHPx-P), and the phospholipid hydroperoxide glutathione peroxidase GPX4 (PHGPX), were hybridized to Southern blots containing genomic DNA from human x hamster somatic cell hybrids. GPX2 was mapped to chromosome 14, GPX3 to chromosome 5 and GPX4 to chromosome 19. Additionally, human chromosomes 3 and 21 and the X chromosome were shown to contain sequences homologous to GPX1, as reported previously.
 ...
PMID:The human glutathione peroxidase genes GPX2, GPX3, and GPX4 map to chromosomes 14, 5, and 19, respectively. 828 91

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).
 ...
PMID:Expression, characterization, and tissue distribution of a new cellular selenium-dependent glutathione peroxidase, GSHPx-GI. 842 33

Selenium-dependent cellular glutathione peroxidase (GPX1) overexpressing [GPX1(+)] mice were derived by microinjecting a 5.3-kb cloned entire mouse GPX1 genomic DNA into fertilized eggs. The objective of this study was to determine the effect of GPX1 overexpression and dietary selenium on the expression of selenoperoxidases and the status of lipid peroxidation of these transgenic animals. An experiment with a 2 x 2 factorial arrangement of treatments with 15 GPX1(+) and 15 control mice (2 mo old) was conducted for 8 wk. Ten mice of each group (half males and females) were fed a Se-deficient, Torula yeast basal diet (0.02 mg Se/kg, no supplemental vitamin E) and five mice (three males and two females) were fed the basal diet supplemented with 0.51 mg Se/kg as Na2SeO3. The GPX1(+) mice had greater GPX1 activities (one- to sixfold, P < 0.0001) than the control mice at both levels of dietary selenium in all tissues except for liver, in which such difference (100%, P < 0.05) was observed only in Se-deficient mice. The GPX1 mRNA level in kidney and in lung of the Se-deficient GPX1(+) mice was 81% and 7.5-fold greater (P < 0.003) than the respective control level. Overexpression of GPX1 did not alter phospholipid hydroperoxide glutathione peroxidase (GPX4) activities and mRNA levels or glutathione S-transferase (GST) activities in most of the tissues, plasma glutathione peroxidase (GPX3) activity or plasma Se concentrations. No differences in lipid peroxidation in kidney, lung or intestine were observed between the Se-deficient GPX1(+) and control mice. In conclusion, the overexpression of the GPX1 gene in these mice was tissue specific and did not affect the expression of GPX3, GPX4 or GST and plasma Se levels; dietary Se appeared to affect the GPX1 overexpression at its mRNA level.
 ...
PMID:Overexpression of cellular glutathione peroxidase does not affect expression of plasma glutathione peroxidase or phospholipid hydroperoxide glutathione peroxidase in mice offered diets adequate or deficient in selenium. 916 85

Selenium-dependent cellular glutathione peroxidase (GPX1) knockout [GPX1(-)] mice were derived from 129/SVJ x C57BL/6 hybrid mice by microinjecting C57BL/6 blastocysts with recombinant embryonic stem cells carrying a target mutation in the GPX1 gene. Experiment 1 was conducted to determine the effects of the GPX1 knockout on the susceptibility of mice to dietary vitamin E and Se deficiency and on the expression of the Se-dependent plasma glutathione peroxidase (GPX3) and phospholipid hydroperoxide glutathione peroxidase (GPX4), and the Se-independent glutathione S-transferase (GST). Eleven GPX1(-) and 11 control mice (5 wk old, six males and five females) were fed a Se-deficient, Torula yeast basal diet (0.02 mg Se/kg, no supplemental vitamin E) or the basal diet supplemented with 0.5 mg Se/kg (as Na2SeO3) for 13 wk. Experiment 2 was conducted to determine the effect of the GPX1 knockout on the total Se concentration in the liver of Se-adequate mice. Six GPX1(-) and four control mice (5 wk old, half males and females) were fed the basal diet supplemented with 0.2 mg Se/kg and 15 mg of all-rac-alpha-tocopheryl acetate/kg for 5 wk. There was no difference in body weight gain or apparent susceptibility to dietary vitamin E and Se deficiency between the GPX1(-) and control mice. Knockout of GPX1 resulted in almost complete abolishment of GPX1 activity in various tissues, but had no effect on the GPX3 or GPX4 mRNA level and activity or the GST activity in several tissues at either level of dietary Se. The liver total Se concentration in the Se-adequate GPX1(-) mice was only 42% of that in the controls (P < 0. 0001). These results indicate that GPX1 is expressed independently of GPX3 or GPX4 and represents approximately 60% of the total hepatic Se in Se-adequate mice.
 ...
PMID:Cellular glutathione peroxidase knockout mice express normal levels of selenium-dependent plasma and phospholipid hydroperoxide glutathione peroxidases in various tissues. 923 36

It has been observed previously that plasma selenium and glutathione levels are subnormal in HIV-infected individuals, and plasma glutathione peroxidase activity is decreased. Under these conditions the survival rate of AIDS patients is reduced significantly. In the present study, using 75Se-labeled human Jurkat T cells, we show that the levels of four 75Se-containing proteins are lower in HIV-infected cell populations than in uninfected cells. These major selenoproteins migrated as 57-, 26-, 21-, and 15-kDa species on SDS/PAGE gels. In our earlier studies, the 57-kDa protein was purified from T cells and identified as a subunit of thioredoxin reductase. The 26- and 21-kDa proteins were identified in immunoblot assays as the glutathione peroxidase (cGPX or GPX1) subunit and phospholipid hydroperoxide glutathione peroxidase (PHGPX or GPX4), respectively. We recently purified the 15-kDa protein and characterized it as a selenoprotein of unknown function. In contrast to selenoproteins, low molecular mass [75Se]compounds accumulated during HIV infection and migrated as a diffuse band near the front of SDS/PAGE gels.
 ...
PMID:Levels of major selenoproteins in T cells decrease during HIV infection and low molecular mass selenium compounds increase. 992 54

Selenium functions within mammalian systems primarily in the form of selenoproteins. Selenoproteins contain selenium as selenocysteine and perform a variety of physiological roles. Eleven selenoproteins have been identified: cellular or classical glutathione peroxidase; plasma (or extracellular) glutathione peroxidase; phospholipid hydroperoxide glutathione peroxidase; gastrointestinal glutathione peroxidase; selenoprotein P; types 1, 2, and 3 iodothyronine deiodinase; selenoprotein W; thioredoxin reductase; and selenophosphate synthetase. Of these, cellular and plasma glutathione peroxidase are the functional parameters used for the assessment of selenium status. Glutathione peroxidases catalyze the reduction of peroxides that can cause cellular damage. Thioredoxin reductase provides reducing power for several biochemical processes and defends against oxidative stress. Selenoprotein P appears to play a role in oxidant defense. Selenoprotein W may play a role in oxidant defense and be involved with muscle metabolism. Thyroid deiodinases function in the formation and regulation of active thyroid hormone. Selenophosphate synthetase is an enzyme required for the incorporation of selenocysteine into selenoproteins. In addition, a protein in the sperm mitochondrial capsule, which is vital to the integrity of sperm flagella, may be a unique selenoprotein. Recommended intakes, food sources, and status assessment of selenium, as well as selenium's role in health and disease processes, are reviewed.
 ...
PMID:The diverse role of selenium within selenoproteins: a review. 1076 94

We have previously found that L929 cell conditioned medium (L929-CM) could protect mouse peritoneal macrophages from oxidative injury. To uncover the mechanism further, we investigated the effect of L929-CM on the oxidative injury caused by tbOOH to RAW264.7 cell lines. The results showed that L929-CM could protect RAW264.7 cells from oxidative injury (presented by cell morphology and cell survival rate), and L929-CM could also improve total superoxide dismutase (SOD), selenium-dependent and non-selenium-dependent glutathione peroxidase (SeGPx and non-SeGPx) activities in RAW264.7 cells. RT-PCR analysis showed that, L929-CM could induce plasma glutathione peroxidase (PLGPx) mRNA expression, while there was no inducing effect of L929-CM on phospholipid hydroperoxide glutathione peroxidase (PHGPx) mRNA expression in RAW264.7 cells. 5 microg/ml actinomycin D, 30 microg/ml cycloheximide (de novo protein synthesis inhibitor) and 50 microg/ml acetovanilone (intracellular superoxide anion production inhibitor) had no effects in attenuating the induction of PLGPx expression by L929-CM.
 ...
PMID:L929 cell conditioned medium protects RAW264.7 cells from oxidative injury through inducing antioxidant enzymes. 1088 Feb 39

This is the first report to describe the successful detection of human gastrointestinal glutathione peroxidase in normal tissues by Western blotting and immunohistochemical staining techniques. Four hybridoma clones producing monoclonal antibodies (MAbs) against the human gastrointestinal glutathione peroxidase were established from mice immunized with a gastrointestinal glutathione peroxidase-derived peptide. The MAbs did not crossreact with other members of the glutathione peroxidase family, be it cellular glutathione peroxidase, phospholipid hydroperoxide glutathione peroxidase, or extracellular glutathione peroxidase. Although the MAbs were found to react with a 24-kD protein in a Western blotting assay using gastric carcinoma cell extracts as antigen, they did not react with a B-lymphoblastoid cell extract. Immunohistochemical staining showed gastrointestinal glutathione peroxidase localized in the cytoplasm and in the nucleus of gastric carcinoma cells. Moreover, gastrointestinal glutathione peroxidase was detected in tissue extracts of human stomach, small intestine, large intestine, liver, and gallbladder by Western blotting, and its localization was immunohistochemically confirmed in the mucosal epithelia of the basal area of gastric pits and intestinal crypts.
 ...
PMID:Immunohistochemical detection of human gastrointestinal glutathione peroxidase in normal tissues and cultured cells with novel mouse monoclonal antibodies. 1137 22


1 2 Next >>