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

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.
J Mol Endocrinol 1996 Jun
PMID:Selenoenzyme expression in thyroid and liver of second generation selenium- and iodine-deficient rats. 878 84

Rat testis mitochondria contain large amounts of both seleno-enzyme phospholipid hydroperoxide glutathione peroxidase (EC 1.11.1.12, PHGPx) and alpha-tocopherol. The scavenger role of vitamin E consists of transforming the lipoperoxyl radicals into lipid hydroperoxides, thus interrupting the peroxidative cascade. These hydroperoxides are in turn substrates of the PHGPx, which is considered one of the most important specific enzymes capable of protecting, in situ, the membranes from lipid peroxidation. A connection or synergism could, therefore, be envisaged between vitamin and enzyme opposing lipid damage in the mitochondria. Here we present data concerning the HPLC evaluation of vitamin E consumption in rat testis mitochondria and mitochondrial membranes, under different conditions of PHGPx activity, after Fe2+-induced lipid peroxidation. We have found that the enzyme activity, under the conditions tested, does not spare vitamin E from its peroxidation, therefore indicating that the postulated synergism between PHGPx and alpha-tocopherol can be excluded in rat testis mitochondria.
Biochem Mol Med 1996 Aug
PMID:Rat testis mitochondrial phospholipid hydroperoxide glutathione peroxidase does not protect endogenous vitamin E against Fe2+-induced (lipo)peroxidation. 881 43

In this paper we report the isolation and the characterization of a gene encoding the antioxidant enzyme glutathione peroxidase from the human malaria parasite Plasmodium falciparum. This gene contains two introns of 208 and 168 bp and is present in a single copy on chromosome 13. The open reading frame encodes a protein with a predicted length of 205 amino acids, which possesses a potential cleavage site between residues 21 and 22 after a hydrophobic region with the characteristics of a signal sequence. Therefore, the mature protein is predicted to be 184 residues long with a molecular mass of 21404 Da. In comparison with other known glutathione peroxidases many amino acid residues implicated in catalysis are conserved in the malarial enzyme. Phylogenetic analysis indicates that the deduced protein sequence is more closely related to plant glutathione peroxidase and phospholipid hydroperoxide glutathione peroxidase. A 1.5-kb transcript was identified in asynchronous erythrocytic stages.
Mol Biochem Parasitol 1996 Jun
PMID:Molecular characterization of the glutathione peroxidase gene of the human malaria parasite Plasmodium falciparum. 881 93

In rat testis nuclei the activity of the selenoenzyme phospholipid hydroperoxide glutathione peroxidase (PHGPx, EC 1.11.1.12) is much higher than in other tissues and subcellular compartments, with the sole exception of mitochondria. In nuclei, the bound enzyme is solubilized by DNase I treatment, thus suggesting a binding to chromatin. Treatment with ionic strength releases about 70% of bound PHGPx, suggesting that electrostatic bonds are involved. Immunogold electron microscopy indicates the association of PHGPx with chromatin structures in isolated nuclei. A possible interpretation of these data is a PHGPx protective role against DNA peroxidative damage. Furthermore, in agreement with kinetic and structural information, PHGPx-chromatin binding could suggest an hypothetical thiol oxidase activity toward specific thiol bearing proteins which could substitute for GSH as alternative donor substrates. Such activity could give to the enzyme a new important function which is not only protective but also has a specific regulatory function in chromatin condensation.
Biochem Mol Med 1996 Dec
PMID:Phospholipid hydroperoxide glutathione peroxidase (PHGPx) in rat testis nuclei is bound to chromatin. 898 33

The tissue localization and the stage-specific expression of the phospholipid hydroperoxide glutathione peroxidase of Schistosoma mansoni (SmPHGSHpx) have been determined. An antiserum raised against the C-terminal region of the predicted protein sequence was used for immunocytochemical investigations. The native protein is expressed only in female and egg vitelline cells and is practically absent from male worm tissue. Western blot data confirmed these results and showed the complete absence of SmPHGSHpx from cercariae. However, Northern blotting indicated the presence of the corresponding mRNA at all life-cycle stages investigated. The sequence determination of the 5' flanking region of the SmPHGSHpx gene revealed the presence of an extended TATA box (5'-TAAATA-3') at -32, a possible CAAT box at -75 and a putative monomeric estrogen response element 5'-GGTCAA-3' at position -486. In addition, direct and inverted repeat elements are present.
Mol Biochem Parasitol 1996 Jan
PMID:Tissue localization and stage-specific expression of the phospholipid hydroperoxide glutathione peroxidase of Schistosoma mansoni. 899 17

In mammalian selenoprotein mRNAs, the recognition of UGA as selenocysteine requires selenocysteine insertion sequence (SECIS) elements that are contained in a stable stem-loop structure in the 3' untranslated region (UTR). In this study, we investigated the SECIS elements and cellular proteins required for selenocysteine insertion in rat phospholipid hydroperoxide glutathione peroxidase (PhGPx). We developed a translational readthrough assay for selenoprotein biosynthesis by using the gene for luciferase as a reporter. Insertion of a UGA or UAA codon into the coding region of luciferase abolished luciferase activity. However, activity was restored to the UGA mutant, but not to the UAA mutant, upon insertion of the PhGPx 3' UTR. The 3' UTR of rat glutathione peroxidase (GPx) also allowed translational readthrough, whereas the PhGPx and GPx antisense 3' UTRs did not. Deletion of two conserved SECIS elements in the PhGPx 3' UTR (AUGA in the 5' stem or AAAAC in the terminal loop) abolished readthrough activity. UV cross-linking studies identified a 120-kDa protein in rat testis that binds specifically to the sense strands of the PhGPx and GPx 3' UTRs. Direct cross-linking and competition experiments with deletion mutant RNAs demonstrated that binding of the 120-kDa protein requires the AUGA SECIS element but not AAAAC. Point mutations in the AUGA motif that abolished protein binding also prevented readthrough of the UGA codon. Our results suggest that the 120-kDa protein is a significant component of the mechanism of selenocysteine incorporation in mammalian cells.
Mol Cell Biol 1997 Apr
PMID:An RNA-binding protein recognizes a mammalian selenocysteine insertion sequence element required for cotranslational incorporation of selenocysteine. 912 45

We recently isolated stable transfectants expressing human phospholipid hydroperoxide glutathione peroxidase (PHGPx) from the cells of guinea pig cell line 104C1 (Biochem. Biophys. Res. Commun. 219, 486-491, 1996). Among them, one transfectant, designated 104C1/O4C, expressed high glutathione peroxidase activity toward dilinoleoyl phosphatidylcholine hydroperoxide (PCOOH); and another one, 104C1/O2D, moderate activity. In the present study, we investigated the effect of selenium on the PHGPx activity and on the lipid hydroperoxide-mediated cell injury in the transfectants to clarify further the action of PHGPx in preventing oxidative injury of the cells. When transfectant 104C1/O2D cells were cultured in the medium added with 250 nM selenium, glutathione peroxidase activity toward PCOOH increased 8-fold. Western blot analysis also revealed an increase in the amount of protein immunoreactive against anti-rat PHGPx antibody in this transfectant. Lipid hydroperoxide-mediated cell injury to the transfectant 104C1/O2D was significantly suppressed in accordance with the increase in the enzyme activity when the cells were cultured in the medium added with selenium. On the contrary, neither glutathione peroxidase activity toward PCOOH nor susceptibility to the injury was affected by selenium addition to the medium of the parental 104C1 cells, which have no selenium-dependent glutathione peroxidase. These results clearly support our previous conclusion that expression of PHGPx is responsible for the protection of host cells from lipid hydroperoxide-mediated injury.
Biochem Mol Biol Int 1997 Aug
PMID:Effect of selenium on human phospholipid hydroperoxide glutathione peroxidase expression and host cell susceptibility to lipid hydroperoxide-mediated injury. 928 63

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.
J Mol Endocrinol 1998 Apr
PMID:Selenoprotein expression and brain development in preweanling selenium- and iodine-deficient rats. 958 35

Recent findings in our laboratory showed that in citrus cells, salt treatment induced the accumulation of mRNA and a protein corresponding to phospholipid hydroperoxide glutathione peroxidase (PHGPX), an enzyme active in the cellular antioxidant system. The protein and its encoding gene, csa, were isolated and characterized, and the expected enzymatic activity was demonstrated (G. Ben-Hayyim et al., 1993, Plant Sci. 88: 129-140; D. Holland et al., 1993, Plant Mol. Biol. 21: 923-927; D. Holland et al., 1994, FEBS Lett. 337: 52-55; T. Beeor-Tzahar et al., 1995, FEBS Lett. 366: 151-155). In an attempt to find out how salt induces the expression of an antioxidant enzyme, the regulation of PHGPX in citrus cells was studied at both the mRNA transcript and the protein levels. A high and transient response at the csa mRNA level was observed after 4-7 h of exposing salt-sensitive cells to NaCl, or abscisic acid, whereas no response could be detected in the salt-tolerant cells under the same conditions. tert-Butylhydroperoxide, a substrate of PHGPX, induced csa mRNA transcripts after only 2 h, and abolished the differential response between salt-sensitive and salt-tolerant cells. On the basis of these results and those obtained under heat and cold stresses, it is suggested that csa is directly induced by the substrate of its encoded enzyme PHGPX, and that salt induction occurs mainly via the production of reactive oxygen species and hydroperoxides.
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PMID:Regulation of stress-induced phospholipid hydroperoxide glutathione peroxidase expression in citrus 1055 Jun 28

Previous studies of mRNA for classical glutathione peroxidase 1 (GPx1) demonstrated that hepatocytes of rats fed a selenium-deficient diet have less cytoplasmic GPx1 mRNA than hepatocytes of rats fed a selenium-adequate diet. This is because GPx1 mRNA is degraded by the surveillance pathway called nonsense-mediated mRNA decay (NMD) when the selenocysteine codon is recognized as nonsense. Here, we examine the mechanism by which the abundance of phospholipid hydroperoxide glutathione peroxidase (PHGPx) mRNA, another selenocysteine-encoding mRNA, fails to decrease in the hepatocytes and testicular cells of rats fed a selenium-deficient diet. We demonstrate with cultured NIH3T3 fibroblasts or H35 hepatocytes transiently transfected with PHGPx gene variants under selenium-supplemented or selenium-deficient conditions that PHGPx mRNA is, in fact, a substrate for NMD when the selenocysteine codon is recognized as nonsense. We also demonstrate that the endogenous PHGPx mRNA of untransfected H35 cells is subject to NMD. The failure of previous reports to detect the NMD of PHGPx mRNA in cultured cells is likely attributable to the expression of PHGPx cDNA rather than the PHGPx gene. We conclude that 1) the sequence of the PHGPx gene is adequate to support the NMD of product mRNA, and 2) there is a mechanism in liver and testis but not cultured fibroblasts and hepatocytes that precludes or masks the NMD of PHGPx mRNA.
Mol Biol Cell 2001 Apr
PMID:Nonsense-mediated decay of mRNA for the selenoprotein phospholipid hydroperoxide glutathione peroxidase is detectable in cultured cells but masked or inhibited in rat tissues. 1129 3


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