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

We previous reported that a nano red elemental selenium (Nano-Se) in the range from 20 approximately 60 nm had similar bioavailability to sodium selenite (BioFactors 15 (2001) 27). We recently found that Nano-Se with different size had marked difference in scavenging an array of free radicals in vitro, the smaller the particle, the better scavenging activity (Free Radic. Biol. Med. 35 (2003) 805). In order to examine whether there is a size effect of Nano-Se in the induction of Se-dependent enzymes, a range of Nano-Se (5 approximately 200 nm) have been prepared based on the control of elemental Se atom aggregation. The sizes of Nano-Se particles were inversely correlated with protein levels in the redox system of selenite and glutathione. Different sizes of red elemental Se were prepared by adding varying amount of bovine serum albumin (BSA). Three different sizes of Nano-Se (5 approximately 15 nm, 20 approximately 60 nm, and 80 approximately 200 nm) have been chosen for the comparison of biological activity in terms of the induction of seleno-enzyme activities. Results showed that there was no significant size effect of Nano-Se from 5 to 200 nm in the induction of glutathione peroxidase (GPx), phospholipid hydroperoxide glutathione peroxidase (PHGPx) and thioredoxin reductase-1 (TrxR-1) in human hepatoma HepG2 cells and the livers of mice.
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PMID:Nano red elemental selenium has no size effect in the induction of seleno-enzymes in both cultured cells and mice. 1512 May 75

Using a macro array filter with 711 cDNA inserts representing 620 unigenes selected from a barley EST collection, we identified transcripts differentially expressed in salt (NaCl)-treated tolerant (cv. Prasad) and sensitive (cv. Lepakshi) seedlings of foxtail millet (Setaria italica L.). Transcripts of hydrogen peroxide scavenging enzymes such as phospholipid hydroperoxide glutathione peroxidase (PHGPX), ascorbate peroxidase (APX) and catalase 1 (CAT1) in addition to some genes of cellular metabolism were found to be especially up-regulated at high salinity in the tolerant line. To analyse this process at the protein level we examined protein expression patterns under various stress conditions. A 25 kD protein with a pI of 4.8 was found to be induced prominently under high salt concentrations (250 mmol/L). This salt-induced 25 kD protein has been purified and identified by peptide sequencing as PHGPX protein. The increase of the PHGPX protein level under salt stress in the tolerant line parallels the PHGPX mRNA results of array analysis but was more pronounced. We cloned and characterized the foxtail millet PHGPX cDNA, which shows 85% and 95% homology at the DNA and protein level, respectively, to one stress-induced member of the small barley PHGPX gene family encoding non-selenium glutathione peroxidases. As shown by Southern blot analysis, a small family of PHGPX genes exists in foxtail millet, too. The specific expression pattern of the PHGPX gene in salt-induced tolerant millet seedlings suggests that its product plays an important role in the defense reaction against salt-induced oxidative damage and that the characterized glutathione peroxidase is one of the components conferring resistance against salt to the tolerant foxtail millet cultivar.
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PMID:Transcriptome changes in foxtail millet genotypes at high salinity: identification and characterization of a PHGPX gene specifically upregulated by NaCl in a salt-tolerant line. 1512 34

We have established several focal adhesion kinase (FAK) cDNA-transfected HL-60 (HL-60/FAK) cells which were highly resistant to oxidative stress-induced apoptosis. To identify target genes that are involved in HL-60/FAK cells, we performed cDNA microarray screening using apoptosis-chip. There, we identified the decrease of glutathione peroxidase (GPx). This result prompted us to investigate the changes of antioxidant enzymes. Here, we demonstrate that lipid peroxidation was suppressed after treatment with hydrogen peroxide in HL-60/FAK cells but not vector-transfected HL-60 (HL-60/Vect) cells. Furthermore, we demonstrate that HL-60/FAK cells have higher basal reactive oxygen species (ROS) levels than the parental HL-60 or HL-60/Vect cells, while ROS accumulation by hydrogen peroxide treatment was almost the same in these cells. Basal activity and mRNA expression of antioxidant enzymes, particularly of GSH reductase (GRe), phospholipid hydroperoxide glutathione peroxidase (PHGPx) were markedly elevated in HL-60/FAK cells. In contrast, GPx and catalase levels were decreased in HL-60/FAK cells. Further, a Src family kinases inhibitor, PP2, suppressed GRe and PHGPx mRNA by inactivation of FAK and c-Src in HL-60/FAK cells. These results suggest that FAK upregulates antioxidant enzymes and suppresses lipid peroxidation, resulting in the anti-apoptotic state for oxidative stress.
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PMID:Induction of antioxidant enzymes by FAK in a human leukemic cell line, HL-60. 1523 16

The interfacial behavior differences of two glutathione peroxidase isoforms have been investigated. The first isoform is the phospholipid-hydroperoxide glutathione peroxidase (EC 1.11.1.12) (GPx-4) isolated from rat testes and the second one is the cytosolic glutathione peroxidase (EC 1.11.1.9) (GPx-1) from bovine erythrocytes. Injected in the subphase buffer of a Langmuir trough, GPx-4 was able to adsorb quickly at the air-water interface whereas the GPx-1 was not. Then, the protein interaction with phospholipid monolayers was explored. Indeed, a monolayer of phospholipids containing a different number of polyunsaturated fatty acyl chains was prepared at the air-water interface. Under each kind of monolayer, the protein solution was injected and its adsorption was visualized by the measurement of successive pressure-area isotherms. We have, then, determined the molecular area increase due to the protein adsorption. It was found that the GPx-4 is adsorbed in each kind of monolayer tested whereas no molecular area increase was detected with the GPx-1. This indicates that the GPx-4 has a higher affinity for the interface, recovered or not by lipids, than the GPx-1. Moreover, the GPx-4 presents a different affinity for the phospholipid monolayers depending on the number of polyunsaturated fatty acyl chains.
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PMID:Adsorption of a phospholipid-hydroperoxide glutathione peroxidase into phospholipid monolayers at the air-water interface. 1526 Oct 42

A dramatic reduction in the expression of a novel phospholipid hydroperoxide glutathione peroxidase (PHGPx), which incorporates cysteine instead of selenocysteine in the conserved catalytic motif was observed in a microarray analysis using cDNAs amplified from mRNA of Brca1-null mouse embryonic fibroblasts. This non-selenocysteine PHGPx named NPGPx is a cytoplasmic protein with molecular mass of approximately 22 kDa and has little detectable glutathione peroxidase activity in vitro. Ectopic expression of NPGPx in Brca1-null cells that were sensitive to oxidative stress induced by hydrogen peroxide conferred a similar resistance level to that of the wild-type cells, suggesting the importance of this protein in reducing oxidative stress. Expression of NPGPx was found in many tissues, including developing mammary gland. However, the majority of breast cancer cell lines studied (11 of 12) expressed very low or undetectable levels of NPGPx irrespective of BRCA1 status. Re-expression of NPGPx in breast cancer lines, MCF-7 and HCC1937, which have very little or no endogenous NPGPx, induced resistance to eicosapentaenoic acid (an omega-3 type of polyunsaturated fatty acid)-mediated cell death. Conversely, inhibition of the expression of NPGPx by the specific small interfering RNA in HS578T breast cancer cells that originally express substantial amounts of endogenous NPGPx increased their sensitivity to eicosapentaenoic acid-mediated cell death. Thus, NPGPx plays an essential role in breast cancer cells in alleviating oxidative stress generated from polyunsaturated fatty acid metabolism.
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PMID:Identification of a novel putative non-selenocysteine containing phospholipid hydroperoxide glutathione peroxidase (NPGPx) essential for alleviating oxidative stress generated from polyunsaturated fatty acids in breast cancer cells. 1529 5

Levels of antioxidant defenses and lipid peroxidation were evaluated in mussels exposed to lead (200 mg/l), iron (500 microg/l), cadmium (200 microg/l) and copper (40 microg/l), for 12, 24, 72 and 120 h. Glutathione S-transferase (GST) activity was unchanged with all treatments. Catalase (CAT) increased after 120 h of exposure to all metals. Mussels exposed to Cd for 12 h, and to Cu and Fe for 120 h had increased lipid peroxidation, which might be associated to decreased levels of reduced glutathione (GSH) and glutathione peroxidase (GPx) activity. Pb exposure caused GSH depletion after 12 h and increased GPx activity after 120 h. Negative correlations were observed between the enzyme phospholipid hydroperoxide glutathione peroxidase (PHGPx) and malonaldehyde (MDA) levels after Fe and Cu exposure, indicating a protective role of PHGPx against lipid peroxidation, and suggesting the use of this enzyme as a new potential biomarker of toxicity associated with contaminant exposure in mussels.
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PMID:Protective effect of phospholipid hydroperoxide glutathione peroxidase (PHGPx) against lipid peroxidation in mussels Perna perna exposed to different metals. 1532 6

Saccharomyces cerevisiae expresses multiple phospholipid hydroperoxide glutathione peroxidase (PHGPx)-like proteins in the absence of a classical glutathione peroxidase (cGPx), providing a unique system for dissecting the roles of these enzymes in vivo. The Gpx3 (Orp1/PHGpx3) protein transduces the hydroperoxide signal to the transcription factor Yap1, a function that could account for most GPX-dependent phenotypes. To test this hypothesis and ascertain what functions of Gpx3 can be shared by cGPx-like enzymes, we constructed a novel cGPx-like yeast enzyme, cGpx3. We confirmed that the "gap" sequences conserved among cGPxs but absent from aligned PHGPx sequences are the principal cause of the structural and functional differences of these enzymes. Peroxidase activity against a cGPx substrate was high in the cGpx3 construct, which was multimeric and had a peroxidase catalytic mechanism distinct from Gpx3; but cGpx3 was defective for phospholipid hydroperoxidase and signaling activities. cGpx3 did not complement the sensitivity to lipid peroxidation of a gpxDelta mutant, and the resistance to lipid peroxidation conferred by Gpx3 was independent of Yap1, establishing a functional role for Gpx3 phospholipid hydroperoxidase activity. Using the comparison between cGpx3 and Gpx3 in conjunction with other constructs to probe lipid peroxidation as a toxicity mechanism, we also ascertained that lipid peroxidation-dependent processes are a principal cause of cellular cadmium toxicity. The results demonstrate that phospholipid hydroperoxidase and Yap1-mediated signaling activities of Gpx3 have independent functional roles, although both functions depend on the absence of cGPx-like subunit interaction sites, and the results resolve more clearly the potential drivers of the differential selective evolution of GPx-like enzymes.
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PMID:Genetic dissection of the phospholipid hydroperoxidase activity of yeast gpx3 reveals its functional importance. 1533 45

Phospholipid hydroperoxide glutathione peroxidase is a monomeric Se-peroxidase highly expressed in mammalian male germ cells. Its nuclear form, sperm nuclei glutathione peroxidase (snGPx), has been originally identified in maturating spermatozoa as a transcription product containing an alternative exon within the phospholipid hydroperoxide glutathione peroxidase gene. In this paper, we show that this form is inconstantly detectable in rat spermatozoa where a 20.0 and 25.9 kDa major forms are detected instead. These have been conclusively characterized. The N-terminus sequence of the 20.0 kDa form confirmed that the protein is identical to cytosolic form, suggesting diffusion into the nucleus. The 25.9 kDa protein represented a truncated form of the previously described nuclear snGPx, lacking the basic nuclear localization signal. This protein is present in two forms differing from each other by the presence of an N-terminal methionine. The presence of traces of the larger snGPx form suggests that exhaustive proteolytic processing of the precursor produces the 25.9 kDa enzyme, although the alternate use of a downstream ATG, at least in rodents, could not be unequivocally ruled out.
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PMID:Primary structure of the nuclear forms of phospholipid hydroperoxide glutathione peroxidase (PHGPx) in rat spermatozoa. 1567 Aug 26

Thioredoxin reductases (TRs) are important redox regulatory enzymes, which control the redox state of thioredoxins. Mammals have cytosolic and mitochondrial TRs, which contain an essential selenocysteine residue and reduce cytosolic and mitochondrial thioredoxins. In addition, thioredoxin/glutathione reductase (TGR) was identified, which is a fusion of an N-terminal glutaredoxin domain and the TR module. Here we show that TGR is expressed at low levels in various tissues but accumulates in testes after puberty. The protein is particularly abundant in elongating spermatids at the site of mitochondrial sheath formation but is absent in mature sperm. We found that TGR can catalyze isomerization of protein and interprotein disulfide bonds and localized this function to its thiol domain. TGR targets include proteins that form structural components of the sperm, including glutathione peroxidase GPx4/PHGPx. Together, TGR and GPx4 can serve as a novel disulfide bond formation system. Both enzymes contain a catalytic selenocysteine consistent with the role of selenium in male reproduction.
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PMID:Mammalian selenoprotein thioredoxin-glutathione reductase. Roles in disulfide bond formation and sperm maturation. 1590 30

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+.
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PMID:GPX2, encoding a phospholipid hydroperoxide glutathione peroxidase homologue, codes for an atypical 2-Cys peroxiredoxin in Saccharomyces cerevisiae. 1625 Nov 89


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