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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 reaction of phospholipid hydroperoxide glutathione peroxidase (PHGPx) and Ebselen with phospholipid and cholesterylester hydroperoxides associated with HDLox and LDLox was investigated using specific HPLC assays for the hydroperoxides of phosphatidylcholine (PCOOH) and cholesteryllinolate (Ch18:2-OOH) and for cholesteryllinolate hydroxides (Ch18:2-OH). HDLox and LDLox were formed from the corresponding isolated native lipoproteins by controlled and limited oxidation initiated by aqueous peroxyl radicals. Incubation of HDLox or LDLox in the presence of PHGPx/GSH or Ebselen/GSH resulted in rapid degradation of both classes of lipid hydroperoxides, with equimolar amounts of Ch18:2-OH formed from Ch18:2-OOH. No pronounced differences were observed between PCOOH and Ch18:2-OOH in terms of substrate specificity, whereas HDLox-associated PCOOH and Ch18:2-OOH appeared to be slightly better substrates for PHGPx/GSH as compared to those in LDLox. Also, Ch18:2-OOH associated with HDLox but not LDLox were reduced by Ebselen or GSH alone. These in vitro findings indicate that the enzymatic PHGPx/GSH and the nonenzymatic Ebselen/GSH systems can efficiently reduce hydroperoxides of phospholipids and cholesterylesters associated with intact lipoproteins.
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PMID:Reduction of HDL- and LDL-associated cholesterylester and phospholipid hydroperoxides by phospholipid hydroperoxide glutathione peroxidase and Ebselen (PZ 51). 813 30

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.
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PMID:Reactivity of plasma glutathione peroxidase with hydroperoxide substrates and glutathione. 823 61

The comparative importance of phospholipid hydroperoxide glutathione peroxidase (PHGPx) and of "classic" glutathione peroxidase (GPx) in the reduction of phospholipid hydroperoxides is unclear. Although GPx activity is 500-fold higher than that of PHGPx in rat liver, the reduction of phospholipid hydroperoxides by glutathione (GSH) through GPx may be strongly limited by a low PLA2 activity. We address this issue using a moderately detailed kinetic model of mitochondrial lipid peroxidation in rat liver. The model was based on published data and was subjected to validation as reported in the references. It is analysed by computer simulation and sensitivity analysis. Results suggest that in rat liver mitochondria PHGPx is responsible for almost all phospholipid hydroperoxide reduction. Under physiological conditions, the estimated flux of phospholipid hydroperoxides reduction through PHGPx is about four orders of magnitude higher than the estimated hydrolysis flux through PLA2. On the other hand, virtually all hydrogen peroxide is reduced through GPx. Therefore, a functional complementarity between PHGPx and GPx is suggested. Because the results are qualitatively robust to changes of several orders of magnitude in PLA2 and PHGPx levels, the conclusions may not be limited to mitochondria.
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PMID:PHGPx and phospholipase A2/GPx: comparative importance on the reduction of hydroperoxides in rat liver mitochondria. 852 27

Singlet oxygen (1O2)-mediated photooxidation of cholesterol gives three hydroperoxide products: 3 beta-hydroxy-5 alpha-cholest-6-ene-5-hydroperoxide (5 alpha-OOH), 3 beta-hydroxycholest-4-ene-6 alpha-hydroperoxide (6 alpha-OOH) and 3 beta-hydroxycholest-4-ene-6 beta-hydroperoxide (6 beta-OOH). These species have been compared with respect to photogeneration rate on the one hand and susceptibility to enzymatic reduction/detoxification on the other, using the erythrocyte ghost as a cholesterol-containing test membrane and chloroaluminum phthalocyanine tetrasulfonate (AlPcS4) as a 1O2 sensitizer. Peroxide analysis was accomplished by high-performance liquid chromatography with mercury cathode electrochemical detection (HPLC-EC[Hg]). The initial rate of 5 alpha-OOH accumulation in AlPcS4/light-treated ghosts was found to be about three times greater than that of 6 alpha-OOH or 6 beta-OOH. Membranes irradiated in the presence of ascorbate and ferric-8-hydroxyquinoline (Fe[HQ]2, a lipophilic iron complex) accumulated lesser amounts of 5 alpha-OOH, 6 alpha-OOH and 6 beta-OOH but relatively large amounts of another peroxide pair, 3 beta-hydroxycholest-5-ene-7 alpha- and 7 beta-hydroperoxide (7 alpha, 7 beta-OOH), suggestive of iron-mediated free radical peroxidation. When photoperoxidized membranes containing 5 alpha-OOH, 6 alpha,6 beta-OOH and 7 alpha,7 beta-OOH (arising from 5 alpha-OOH rearrangement) were incubated with glutathione (GSH) and phospholipid hydroperoxide glutathione peroxidase (PHGPX), all hydroperoxide species underwent HPLC-EC(Hg)-detectable reduction to alcohols, the relative first order rate constants being as follows: 1.0 (5 alpha-OOH), 2.0 (7 alpha,7 beta-OOH), 2.4 (6 alpha-OOH) and 3.2 (6 beta-OOH).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Photodynamically generated 3-beta-hydroxy-5 alpha-cholest-6-ene-5- hydroperoxide: toxic reactivity in membranes and susceptibility to enzymatic detoxification. 857 Jul 16

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.
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PMID:Phospholipid hydroperoxide glutathione peroxidase (PHGPx) in rat testis nuclei is bound to chromatin. 898 33

The family of glutathione peroxidases encompasses, as far, three tetrameric glutathione peroxidases (GPx) and the monomeric PHGPx. Although the overall homology between tetrameric enzymes and PHGPx is less than 30%, a pronounced similarity has been detected on clusters involved in the active site and a common catalytic triad (selenocysteine glutamine and tryptophan) has been defined by structural and kinetic data. A major peculiar feature of the reaction catalyzed by PHGPx is the possibility to accommodate large lipophilic substrates. This accounts for the observed dramatic antiperoxidant effect and the synergism with vitamin E. Moreover, the reduction of lipid hydroperoxides accounts also for the observed modulation of cycloxygenase and inhibition of 15-lipoxygenase. On the other hand, structural and kinetic data indicate that also the specificity of PHGPx for the donor substrate is not restricted to GSH and the recent observation the PHGPx binds to specific mitochondrial proteins, from which it is released by ionic strength and thiols, suggests a possible fole of this selenoenzyme in catalyzing the specific oxidation of protein thiols, thus modulating the activity of cellular regulatory elements. On this light, the selenium mojety of PHGPx, reacting much faster that thiols with a peroxide, and then oxidizing specific protein thiols, would channel the oxidation toward protein targets, thus providing, by protein-protein interaction, the specificity of the redox transition.
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PMID:Phospholipid hydroperoxide glutathione peroxidase (PHGPx): more than an antioxidant enzyme? 931 26

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

Identification of signature products provides a powerful means for establishing whether singlet molecular oxygen (1O2) is a reactive intermediate in a photodynamic process. This approach is particularly attractive for biological systems in which direct physical measurement is difficult because of the short lifetime of 1O2. Among the many possible reporter molecules in a target system, cholesterol (Ch) has the advantage of affording a limited number of readily distinguishable oxidation products, among which are the hydroperoxides 3 beta-hydroxy-5 alpha-cholest-6-ene-5-hydroperoxide (5 alpha-OOH), 3 beta-hydroxycholest-4-ene-6 alpha-hydroperoxide (6 alpha-OOH) and 3 beta-hydroxycholest-4-ene-6 beta-hydroperoxide (6 beta-OOH) that derive specifically from 1O2 addition. The purpose of this study was to compare these species in terms of (1) rates of accumulation in photodynamically treated liposomal membranes; (2) susceptibility to iron-mediated 1 e- reduction that triggers chain peroxidative damage; (3) susceptibility to selenoperoxidase (phospholipid hydroperoxide glutathione peroxidase [PHGPX])-mediated 2 e- reduction that protects against such damage and (4) relative toxicity to mammalian cells. Our results indicate that 5 alpha-OOH is photogenerated at a much greater initial rate than 6 alpha-OOH or 6 beta-OOH. Although liposomal 5 alpha-OOH, 6 alpha-OOH, and 6 beta-OOH exhibit similar first-order decay kinetics during iron/ascorbate treatment, the former decays much more slowly during GSH/PHGPX treatment, and is more toxic to L1210 cells. These and related findings suggest that 5 alpha-OOH is potentially the most damaging ChOOH to arise in photodynamically treated cells.
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PMID:Singlet oxygen adducts of cholesterol: photogeneration and reductive turnover in membrane systems. 1054 45

The partially purified phospholipid hydroperoxide glutathione peroxidase (PHGPx) from A431 cells was used to systematically compare the inhibitory effect on the enzyme activity of various lipoxygenases and cyclooxygenases. Under the standard assay system, platelet 12-lipoxygenase, 15-lipoxygenase, and cyclooxygenase-2 were the most sensitive to the inhibition by PHGPx. 5-Lipoxygenase and cyclooxygenase-1 were less sensitive to the inhibition by PHGPx than platelet 12-lipoxygenase and cyclooxygenase-2, respectively, and the difference was approximately 10-fold. Reduction of 12(S)-hydroperoxyeicosatetraenoic acid to 12(S)-hydroxyeicosatetraenoic acid by PHGPx was observed in the presence of glutathione (GSH), and the inhibitory effect of PHGPx on 12-lipoxygenase-catalyzed arachidonate metabolism was reversed by the addition of exogenous lipid hydroperoxide. The results indicate that PHGPx directly reduced lipid hydroperoxides and then down-regulated the activity of arachidonate oxygenases. Moreover, a high-level expression of PHGPx mRNA and its 12-lipoxygenase-inhibitory activity was observed in cancer cells and endothelial cells, and these results suggest that PHGPx may play a significant role in the regulation of reactive oxygen species formation in these cells.
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PMID:Inhibitory effect of phospholipid hydroperoxide glutathione peroxidase on the activity of lipoxygenases and cyclooxygenases. 1056 Jun 10

Regulation of arachidonate metabolism in human epidermoid carcinoma A431 cells by phospholipid hydroperoxide glutathione peroxidase (PHGPx) and cytosolic glutathione peroxidase (GPx1) was studied. In order to study the effect of reduced glutathione (GSH) on the catalysis regulation of these oxygenation enzymes, diethyl maleate was used to deplete the intracellular GSH. In the presence of 13-hydroperoxyoctadecadienoic acid, the enzymatic catalysis of cyclooxygenase and 12-lipoxygenase was significantly increased in the GSH-depleted cells. In terms of the inhibitory effect on 12-lipoxygenase, PHGPx was more sensitive to GSH concentrations than GPx1. Inhibition of PHGPx activity by the treatment of cells with antisense oligonucleotide of PHGPx mRNA increased the enzymatic catalysis of both cyclooxygenase and 12-lipoxygenase. In conclusion, the results indicate that catalysis of cyclooxygenase and 12-lipoxygenase in A431 cells was regulated by redox-reaction, and PHGPx seems to play an important role in the controlling of these reactions.
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PMID:Regulation of cyclooxygenase and 12-lipoxygenase catalysis by phospholipid hydroperoxide glutathione peroxidase in A431 cells. 1088 92


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