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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 (GPx) are characterized by a catalytically active selenium which forms the center of a strictly conserved triad composed of selenocysteine, glutamine, and tryptophan. In order to check the functional relevance of this structural peculiarity, six molecular mutants of phospholipid hydroperoxide glutathione peroxidase (PHGPx) were designed, isolated, and investigated kinetically. Replacement of the selenocysteine in position 46 by cysteine decreased k + 1, i.e., the reaction rate of reduced enzyme with hydroperoxide, by three orders of magnitude. The rate of regeneration of the reduced enzyme by glutathione (k' + 2) was similarly affected. Additional substitution of Gln81 or Trp136 by acid residues resulted in a further decrease of k + 1 by three orders of magnitude, whereas histidine or neutral residues in these positions proved to be less deleterious. The data support the hypothesis that the typical triad of selenocysteine, glutamine, and tryptophan is indeed a novel catalytic center in which the reactivity of selenium is optimized by hydrogen bonding provided by the adjacent glutamine and tryptophan residues.
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PMID:Probing the presumed catalytic triad of a selenium-containing peroxidase by mutational analysis. 955 42

Two hours after its addition to cultures of a guinea pig cell line, 104C1, dilinoleoyl phosphatidylcholine monohydroperoxide (PCOOH) at concentrations of 5-160 microM induced a dissipation of the mitochondrial inner membrane potential (delta psi m), without any apparent morphological changes, in the cells. The PCOOH-induced loss of delta psi m was restored 4 hr after the replacement of the medium with PCOOH-free fresh medium. In contrast, 104C1/O4C cells, a stable clone from 104C1 cells transfected with the human phospholipid hydroperoxide glutathione peroxidase (PHGPx) gene encoding a sequence including a signal peptide towards mitochondria, were resistant to the loss of delta psi m after a 2-hr exposure to PCOOH at concentrations up to 160 microM. Even after an 8-hr exposure to 80 microM PCOOH, the transfected cells retained their delta psi m intact, though the parent cells were killed by the same treatment. The present results strongly suggest that the expression of PHGPx protected the host cells from PCOOH-mediated injury at least by protecting their mitochondria from lipid hydroperoxide-induced loss of delta psi m.
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PMID:Dissipation of mitochondrial membrane potential by exogenous phospholipid monohydroperoxide and protection against this effect by transfection of cells with phospholipid hydroperoxide glutathione peroxidase gene. 957 Nov 89

Selenium deficiency causes further impairment of thyroid hormone metabolism in iodine-deficient rats and therefore could have a role in the aetiology of both myxoedematous and neurological cretinism in humans. Thyroidal type I iodothyronine deiodinase (ID-I), cytosolic glutathione peroxidase and phospholipid hydroperoxide glutathione peroxidase activities were increased in iodine-deficient adult rats and their offspring at 11 days of age. Thyroidal ID-I activity was unchanged and thyroidal cytosolic glutathione peroxidase activity was decreased by more than 75% by combined selenium and iodine deficiency in 11-day-old rats, indicating that, while the thyroid retained an ability to produce 3,3',5-triiodothyronine (T3), the gland was probably more susceptible to peroxidative damage caused by increased hydrogen peroxide concentrations driven by increased thyrotrophin. Thyroidal atrophy, common in myxoedematous cretinism, did not occur in iodine- or selenium and iodine-deficient rat pups. Iodine deficiency increased brain type II iodothyronine deiodinase activity 1.5-fold in 4-day-old rats and 3-fold in 11-day-old rats, regardless of selenium status. Thus rats were able to activate compensatory mechanisms in brain that would maintain T3 concentrations in selenium and iodine deficiencies. Surprisingly, however, selenium deficiency had a greater effect than iodine deficiency on markers of brain development in rat pups. Expression of the brain-derived neurotrophic factor (BDNF) mRNA was decreased in selenium deficiency in 4- and 11-day-old pups and in combined selenium and iodine deficiency in 4-day-old pups. Iodine deficiency caused an increase in BDNF expression in 11-day-old pups but had no effect on 4-day-old pups. Myelin basic protein mRNA expression in brain was decreased by combined selenium and iodine deficiency in 11-day-old rats.
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PMID:Selenoprotein expression and brain development in preweanling selenium- and iodine-deficient rats. 958 35

To determine the expression pattern of phospholipid hydroperoxide glutathione peroxidase (PHGPx) mRNA in testes, Northern (3-, 8-, 40-, and 80-wk-old mice) and in situ (8-wk-old mice) hybridization analyses using digoxigenin-labeled RNA probes for PHGPx were performed in the testes of ICR mice. PHGPx mRNA in the mouse testes was first expressed at 3 wk of age, greatly increased at 8 wk, and persisted at the high level until 80 wk. According to in situ analysis, the PHGPx mRNA was expressed stage-specifically during spermatogenesis. It first appeared in pachytene spermatocytes of stage X, gradually increased in round spermatids during early spermiogenesis, and reached a peak in step 10-11 elongating spermatids. After step 12, PHGPx mRNA began to show a progressive decline in the spermatids and was weakly detected in step 16 spermatids. However, the signal was not detected in spermatogonia or early spermatocytes. On the other hand, according to in situ and reverse transcription-polymerase chain reaction analyses, PHGPx mRNA was also expressed in Leydig cells. These findings suggest that PHGPx in testes may be closely involved in spermatogenesis as well as having a general antioxidant function.
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PMID:Expression pattern of phospholipid hydroperoxide glutathione peroxidase messenger ribonucleic acid in mouse testis. 960 63

Classical glutathione peroxidase (GPX1) mRNA levels can decrease to less than 10% in selenium (Se)-deficient rat liver. The cis-acting nucleic acid sequence requirements for Se regulation of GPX1 mRNA levels were studied by transfecting Chinese hamster ovary (CHO) cells with GPX1 DNA constructs in which specific regions of the GPX1 gene were mutated, deleted, or replaced by comparable regions from unregulated genes such as phospholipid hydroperoxide glutathione peroxidase (GPX4). For each construct, stable transfectants were pooled two weeks after transfection, divided into Se-deficient (2 nM Se) or Se-adequate (200 nM Se) medium, and grown for an additional four days. On day of harvest, Se-deficient GPX1 and GPX4 activities averaged 13 +/- 2% and 15 +/- 2% of Se adequate levels, confirming that cellular Se status was dramatically altered by Se supplementation. RNA was isolated from replicate plates of cells and transfected mRNA levels were specifically determined by RNase protection assay. Analysis of chimeric GPX1/GPX4 constructs showed that the GPX4 3'-UTR can completely replace the GPX1 3'-UTR in Se regulation of GPX1 mRNA. We did not find any GPX1 coding regions that could be replaced by the corresponding GPX4 coding regions without diminishing or eliminating Se regulation of the transfected GPX1 mRNA. Further analysis of the GPX1 coding region demonstrated that the GPX1 Sec codon (UGA) and the GPX1 intron sequences are required for full Se regulation of transfected GPX1 mRNA levels. Mutations that moved the GPX1 Sec codon to three different positions within the GPX1 coding region suggest that the mechanism for Se regulation of GPX1 mRNA requires a Sec codon within exon 1. Lastly, we found that addition of the GPX1 3'-UTR to beta-globin mRNA can convey significant Se regulation to beta-globin mRNA levels when a UGA codon is placed within exon 1. We conclude that Se regulation of GPX1 mRNA requires a functional selenocysteine insertion sequence (SECIS) in the 3'-UTR and a Sec codon followed by an intron.
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PMID:Cis-acting elements are required for selenium regulation of glutathione peroxidase-1 mRNA levels. 967 Oct 54

A cDNA was isolated from pea leaf RNA which encodes a phospholipid hydroperoxide glutathione peroxidase (PHGPX; E.C. 1.1.1.1.9). The N-terminal section of this PHGPX encodes a recognisable chloroplast transit peptide. Efficient import in vitro of the pre-PHGPX protein into the stroma of isolated pea chloroplasts confirmed that the PHGPX is a chloroplast-located enzyme. The pea PHGPX has highly conserved homologues in Arabidopsis, citrus and Nicotiana sylvestris and the authors suggest that these proteins are also localised in the chloroplast and not in the cytosol as previously supposed.
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PMID:Identification of cDNAS encoding plastid-targeted glutathione peroxidase. 968 Sep 87

We have previously shown that changes in glutathione peroxidase-1 (GPX1; H2O2:oxidoreductase, EC 1.11.1.9), plasma thyroid hormone and glutathione-S-transferase were not associated with changes in growth observed in second-generation (F2) severely Se-deficient rats; we also found that liver phospholipid hydroperoxide glutathione peroxidase (GPX4; EC 1.11.1.12) activity falls in first-generation (F1) Se-deficient rats to 41% of levels in Se-adequate rats. The purposes of this study were to determine the effect of F2 Se deficiency on GPX4 and to detect early changes in Se parameters associated with growth after single, small Se injections. Se-deficient male F2 weanling rats were randomly divided into two groups and fed a Se-deficient crystalline amino acid (0.003 microg Se/g diet; -Se) diet or that diet supplemented for 14 d with 0.2 microg Se/g diet (+Se) as Na2SeO3. Growth of -Se rats was 55% of the rate of +Se rats. Liver Se, GPX1 activity, GPX4 activity and testis GPX4 activity in -Se rats at 14 d were 1, 2, 23 and 13%, respectively, of levels in +Se rats. In a series of experiments, additional F2 male weanling rats were fed the -Se diet for 14 d and then were given an intraperitoneal single saline injection of 0, 1 or 5 microg Se/100 g body weight (BW) as Na2SeO3 and killed 1 or 7 d later. Rats injected with 1 or 5 microg Se/100 g BW grew 36 or 48%, respectively, above the rate of saline-injected rats. Liver Se concentration increased 367% and testis GPX4 activity doubled in rats 1 d after injection of 1 microg Se/100 g BW compared with saline-injected rats; these parameters were further elevated with 5 microg Se/100 g BW injections. Increases in liver Se and testis GPX4 activity were the parameters best associated with improved growth after Se injection, but the molecular role for Se in growth remains unclear.
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PMID:Liver selenium and testis phospholipid hydroperoxide glutathione peroxidase are associated with growth during selenium repletion of second-generation Se-deficient male rats. 968 46

The oxidation of low density lipoprotein (LDL) by mammalian 15-lipoxygenases (15-LOX) was implicated in early atherogenesis. We investigated the molecular mechanism of 15-LOX/LDL interaction and found that during short term incubations, LDL cholesterol esters are oxygenated preferentially by the enzyme. Even when the LDL particle was loaded with free linoleic acid, cholesteryl linoleate constituted the major LOX substrate. In contrast, only small amounts of free oxygenated fatty acid isomers were detected, and re-esterification of oxidized fatty acids into the LDL ester lipid fraction was ruled out. When LDL was depleted from alpha-tocopherol, specific oxygenation of the cholesterol esters was not prevented, and the product pattern was not altered. Similar results were obtained at low (LDL/LOX ratio of 1:1) and high LOX loading (LDL/LOX ratio of 1:10) of the LDL particle. During long term incubations (up to 24 h), a less specific product pattern was observed. However, when the hydroperoxy lipids formed by the 15-LOX were immediately reduced by the phospholipid hydroperoxide glutathione peroxidase, when the reaction was carried out with vitamin E-depleted LDL, or when the assay sample was diluted, the specific pattern of oxygenation products was retained over a long period of time. These data suggest that mammalian 15-LOX preferentially oxidize LDL cholesterol esters, forming a specific pattern of oxygenation products. During long term incubations, free radical-mediated secondary reactions, which lead to a more unspecific product pattern, may become increasingly important. These secondary reactions appear to be suppressed when the hydroperoxy lipids formed are immediately reduced, when alpha-tocopherol-depleted LDL was used, or when the incubation sample was diluted. It may be concluded that 15-LOX-initiated LDL oxidation constitutes a dual-type oxygenase reaction with an initial enzymatic and a subsequent nonenzymatic phase. The biological relevance of this dual-type reaction for atherogenesis will be discussed.
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PMID:The rabbit 15-lipoxygenase preferentially oxygenates LDL cholesterol esters, and this reaction does not require vitamin E. 972 53

Mammalian caput and cauda epididymidal spermatozoa exhibit diverse stages of maturation, and their plasma membrane shows diverse composition and stability levels, thus enabling these spermatozoa to undergo the acrosomal reaction after transit through the epididymis. As a result, the study of antiperoxidative mechanisms is quite relevant, since epididymal spermatozoa must be properly protected against agents such as reactive oxygen species, which can impair the complex maturation process. We considered activities of certain enzymes (glutathione peroxidase [GPx], phospholipid hydroperoxide glutathione peroxidase [PHGPx], glutathione reductase [GR], superoxide dismutase [SOD], and catalase [CAT]) and the vitamin E content in isolated rat caput and cauda epididymidal spermatozoa. The results indicate that caput epididymidal sperm have significantly greater PHGPx (3.5x), GPx (2.4x), and SOD (1.7x) activities, as well as a greater amount of vitamin E (3.8x). There were no detectable differences in the GR and CAT activities of caput and cauda epididymidal spermatozoa. The substantial drop in PHGPx activity during epididymal transit is discussed in relation to an additional function of this enzyme: the use of caput sperm protamines as a sulfhydryl substrate. In vitro peroxidation of the two sperm populations by the free radical generator (azo-initiator) 2,2'-azobis(2-amidinopropane) dihydrochloride revealed that only about 13% of the vitamin E content of the caput epididymidal spermatozoa was consumed, which contrasts with the greater consumption (about 70%) of the vitamin in cauda epididymidal spermatozoa. Selective inhibition of PHGPx, SOD, or CAT did not change this picture. The higher susceptibility of cauda epididymidal spermatozoa to radicals is discussed in relation to the diverse enzymatic activities, vitamin E content, and peroxidative response. These factors are correlated with the different stages of sperm cell maturation, which are characterized-from caput to cauda epididymidis-by progressive destabilization of the plasma and acrosomal membranes.
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PMID:Antioxidant systems in rat epididymal spermatozoa. 974 22

In the absence of a sodium selenite supplement, FRTL-5 cells showed a reduced activity of cytosolic glutathione peroxidase (cGSH-Px), a marker of selenium status, indicating the cells were Se-deficient. Se-deficient cells showed a 65% reduction in cGSH-Px mRNA abundance but little change in abundance of either phospholipid hydroperoxide glutathione peroxidase or type 1 deiodinase (IDI) mRNA. In Se-replete cells increased thyroid stimulating hormone (TSH) caused a small decrease in IDI abundance but in Se-deficient cells TSH caused a large increase. The results indicate an interaction between TSH and Se status in the regulation of thyroid selenoenzyme synthesis.
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PMID:Thyroid stimulating hormone and selenium supply interact to regulate selenoenzyme gene expression in thyroid cells (FRTL-5) in culture. 982 63


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