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

Salt damage to plants has been attributed to a combination of several factors including mainly osmotic stress and the accumulation of toxic ions. Recent findings in our laboratory showed that phospholipid hydroperoxide glutathione peroxidase (PHGPX), an enzyme active in the cellular antioxidant system, was induced by salt in citrus cells and mainly in roots of plants. Following this observation we studied the two most important enzymes active in elimination of reactive oxygen species, namely, superoxide dismutase (SOD) and ascorbate peroxidase (APX), to determine whether a general oxidative stress is induced by salt. While Cu/Zn-SOD activity and cytosolic APX protein level were similarly induced by salt and methyl viologen, the response of PHGPX and other APX isozymes was either specific to salt or methyl viologen, respectively. Unlike PHGPX, cytosolic APX and Cu/Zn-SOD were not induced by exogenously added abscisic acid. Salt induced a significant increase in SOD activity which was not matched by the subsequent enzyme APX. We suggest that the excess of H2O2 interacts with lipids to form hydroperoxides which in turn induce and are removed by PHGPX. Ascorbate peroxidase seems to be a key enzyme in determining salt tolerance in citrus as its constitutive activity in salt-sensitive callus is far below the activity observed in salt-tolerant callus, while the activities of other enzymes involved in the defence against oxidative stress, namely SOD, glutathione reductase and PHGPX, are essentially similar.
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PMID:Salt and oxidative stress: similar and specific responses and their relation to salt tolerance in citrus. 942 31

The overexpression of phospholipid hydroperoxide glutathione peroxidase (PHGPx) by RBL-2H3 cells was used as the basis for an investigation of the effects of PHGPx on the formation of leukotrienes. The rates of production of leukotriene C4 (LTC4) and leukotriene B4 (LTB4) in cells that overexpressed PHGPx were 8 times lower than those in a control line of cells. The reduction in rates of production of leukotrienes apparently resulted from the increase in the PHGPx activity since control rates of formation of leukotrienes could be achieved in PHGPx-overexpressing cells upon inhibition of PHGPx activity by diethyl malate. The conversion of radioactively labeled arachidonic acid to intermediates in the lipoxygenase pathway, such as 5-hydroxyeicosatetraenoic acid (5-HETE), LTC4, and LTB4, was strongly inhibited in PHGPx-overexpressing cells that had been prelabeled with [14C]arachidonic acid. PHGPx apparently inactivated the 5-lipoxygenase that catalyzed the conversion of arachidonic acid to 5-hydroperoxyeicosatetraenoic acid (5-HPETE) since 5-HPETE is a common precursor of 5-HETE, LTC4, and LTB4. The rates of formation of LTC4 and LTB4 in PHGPx-overexpressing cells returned to control rates upon the addition of a small amount of 12-HPETE. Flow cytometric analysis revealed that the rapid burst of formation of lipid hydroperoxides induced by A23187 was suppressed in PHGPx-overexpressing cells as compared with the control lines of cells. Subcellular fractionation analysis showed that the amount of PHGPx associated with nuclear fractions from PHGPx-overexpressing cells was 3.5 times higher than that from the control line of cells. These results indicate that PHGPx might be involved in inactivation of 5-lipoxygenase via reductions in levels of the fatty acid hydroperoxides that are required for the full activation of 5-lipoxygenase. Thus, in addition to its role as an antioxidant enzyme, PHGPx appears to have a novel function as a modulator of the production of leukotrienes.
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PMID:Suppression of leukotriene formation in RBL-2H3 cells that overexpressed phospholipid hydroperoxide glutathione peroxidase. 944 35

An Arabidopsis cDNA encoding putative phospholipid hydroperoxide glutathione peroxidase (PHGPX) was cloned and sequenced. The cDNA comprised 803 bp and included an open reading frame which encodes a polypeptide of 169 amino acid residues. The deduced amino acid sequence showed about 80 and 50% homology with plant putative PHGPXs and mammalian PHGPXs, respectively. Southern blot analysis suggested that putative PHGPX gene was a single-copy gene. The expression profile of the putative PHGPX in Arabidopsis under NaCl and Al/Fe treatments, which generate oxidative stress, was analyzed. Northern blot analysis revealed that the Arabidopsis putative PHGPX mRNA levels were increased about 3 and 4.5 times after exposure to NaCl and Al/Fe, respectively. These results suggest that the putative PHGPX gene is induced by oxidative stress in Arabidopsis.
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PMID:Putative phospholipid hydroperoxide glutathione peroxidase gene from Arabidopsis thaliana induced by oxidative stress. 951 Dec 28

An endogenous lipoxygenase inhibitor, purified from the cytosol of human epidermoid carcinoma A431 cells, was analyzed by N-terminal microsequencing and mass spectrometric analysis. The inhibitor was purified by SDS-PAGE, then subjected to in-gel CNBr cleavage and trypsin digestion. The N-terminal sequence data obtained from a 6-8 kDa band of in-gel CNBr cleavage and the three isolated peptides of in-gel trypsin digestion, and the C-terminal peptide sequence from matrix-assisted laser desorption ionization mass spectrometry matched the sequence of human phospholipid hydroperoxide glutathione peroxidase. The purified inhibitor exhibited peroxidase activity using phosphatidylcholine hydroperoxides as the substrate. We therefore concluded that the lipoxygenase inhibitor present in A431 cells was a phospholipid hydroperoxide glutathione peroxidase.
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PMID:Identification of a lipoxygenase inhibitor in A431 cells as a phospholipid hydroperoxide glutathione peroxidase. 953 8

Routine determinations of glutathione peroxidases (GPx) still suffer from poor standardization and usually from lack of specification. The different types of glutathione peroxidases present in cellular homogenates may be differentially estimated by their distinct substrate specificities. Complex lipid hydroperoxides required for this approach, however, are not generally available nor easily standardized due to their molecular heterogeneity and tendency to form micelles. We therefore developed a simple procedure for the differential estimation of the major cellular types of GPx, the cytosolic GPx (cGPx) and the phospholipid hydroperoxide glutathione peroxidase (PHGPx) taking advantage of the peculiar susceptibility of PHGPx to deoxycholate. It proved to reliably determine the activities of both purified cGPx and PHGPx, in mixtures thereof, and in homogenates of tissue samples (e.g., testes), and some (e.g. ECV 304) but not all (e.g. THP-1) cultured cell lines. The method allows the differential estimation of cGPx and PHGPx, if the samples do not contain further types of GPx.
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PMID:Attempt to differentiate between individual glutathione peroxidases in biological samples. 955 40

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

Human glutathione transferases (GSTs) from Alpha (A), Mu (M) and Theta (T) classes exhibited glutathione peroxidase activity towards phospholipid hydroperoxide. The specific activities are in the order: GST A1-1>GST T1-1>GST M1-1>GST A2-2>GST A4-4. Using a specific and sensitive HPLC method, specific activities towards the phospholipid hydroperoxide,1-palmitoyl-2-(13-hydroper oxy-cis-9, trans-11 -octadecadienoyl)-l-3-phosphatidylcholine (PLPC-OOH) were determined to be in the range of 0.8-20 nmol/min per mg of protein. Two human class Pi (P) enzymes (GST P1-1 with Ile or Val at position 105) displayed no activity towards the phospholipid hydroperoxide. Michaelis-Menten kinetics were followed only for glutathione, whereas there was a linear dependence of rate with PLPC-OOH concentration. Unlike the selenium-dependent phospholipid hydroperoxide glutathione peroxidase (Se-PHGPx), the presence of detergent inhibited the activity of GST A1-1 on PLPC-OOH. Also, in contrast with Se-PHGPx, only glutathione could act as the reducing agent for GST A1-1. A GST A1-1 mutant (Arg15Lys), which retains the positive charge between the GSH- and hydrophobic binding sites, exhibited a decreased kcat for PLPC-OOH but not for CDNB, suggesting that the correct topography of the GSH site is more critical for the phospholipid substrate. A Met208Ala mutation, which gives a modified hydrophobic site, decreased the kcat for CDNB and PLPC-OOH by comparable amounts. These results indicate that Alpha, Mu and Theta class human GSTs provide protection against accumulation of cellular phospholipid hydroperoxides.
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PMID:Phospholipid hydroperoxide glutathione peroxidase activity of human glutathione transferases. 957 56

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


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