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)

Severe steroidogenic and spermatogenic alterations are reported in association with diabetic manifestations in humans and experimental animals. This study was planned to determine whether oxidative stress is involved in diabetes-induced alterations in the testes. Diabetes was induced in male rats by injection of 50 mg/kg of streptozotocin (STZ). Ten weeks after injection of STZ, levels of selenium and activities of selenium dependent-glutathione peroxidase (GPx) and phospholipid hydroperoxide glutathione peroxidase (PHGPx) were measured in rat testis. Lipid and protein oxidations were evaluated as measurements of testis malondialdehyde (MDA) and protein carbonyl levels, respectively. Testis sulfydryl (SH) levels were also determined. The control levels of GPx and PHGPx activities were found to be 46.5 +/- 6.2 and 108.8 +/- 19.8 nmol GSH/mg protein/min, respectively. Diabetes caused an increase in testis GPx (65.0 +/- 21.1) and PHGPx (155.9 +/- 43.1) activities but did not affect the levels of selenium or SH. However, the testis MDA and protein carbonyl levels as markers of lipid and protein oxidation, respectively, did not increase in the diabetic group. Aminoguanidine (AG) treatment of diabetic rats returned the testis PHGPx activity (136.5 +/- 24.9) to the control level but did not change the value of GPx activity (69.2 +/- 17.4) compared with diabetic group. MDA and protein carbonyl levels in testis were not affected by AG treatment of diabetic rats, but interestingly AG caused SH levels to increase. The results indicate that reactive oxygen radicals were not involved in possible testicular complications of diabetes because diabetes-induced activations of GPx and PHGPx provided protection against oxidative stress, which was reported to be related to some diabetic complications.
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PMID:Testis glutathione peroxidase and phospholipid hydroperoxide glutathione peroxidase activities in aminoguanidine-treated diabetic rats. 1089 37

A putative glutathione peroxidase gene (Swiss-Prot accession number Z 68200) of Plasmodium falciparum, the causative agent of tropical malaria, was expressed in Escherichia coli and purified to electrophoretic homogeneity. Like phospholipid hydroperoxide glutathione peroxidase of mammals, it proved to be monomeric. It was active with H(2)O(2) and organic hydroperoxides but, unlike phospholipid hydroperoxide glutathione peroxidase, not with phosphatidylcholine hydroperoxide. With glutathione peroxidases it shares the ping-pong mechanism with infinite V(max) and K(m) when analyzed with GSH as substrate. As a homologue with selenocysteine replaced by cysteine, its reactions with hydroperoxides and GSH are 3 orders of magnitude slower than those of the selenoperoxidases. Unexpectedly, the plasmodial enzyme proved to react faster with thioredoxins than with GSH and most efficiently with thioredoxin of P. falciparum (Swiss-Prot accession number 202664). It is therefore reclassified as thioredoxin peroxidase. With plasmodial thioredoxin, the enzyme also displays ping-pong kinetics, yet with a limiting K(m) of 10 microm and a k(1)' of 0.55 s(-)1. The apparent k(1)' for oxidation with cumene, t-butyl, and hydrogen peroxides are 2.0 x 10(4) m(-1) s(-1), 3.3 x 10(3) m(-1) s(-1), and 2.5 x 10(3) m (-1) s(-1), respectively. k(2)' for reduction by autologous thioredoxin is 5.4 x 10(4) m(-1) s(-1) (21.2 m(-1) s(-1) for GSH). The newly discovered enzymatic function of the plasmodial gene product suggests a reconsideration of its presumed role in parasitic antioxidant defense.
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PMID:The putative glutathione peroxidase gene of Plasmodium falciparum codes for a thioredoxin peroxidase. 1108 48

Phospholipid hydroperoxide glutathione peroxidase (PHGPx; EC 1.11.1.12), a broad-spectrum thiol-dependent peroxidase, deserves renewed interest as a regulatory factor in various signaling cascades and as a structural protein in sperm cells. We present a first attempt to identify catalytic intermediates and derivatives of the selenoprotein by liquid chromatography coupled to electrospray tandem mass spectrometry (LC/ESI-MS/MS) and to explain observed specificities by molecular modeling. The ground state enzyme E proved to correspond to position 3-170 of the deduced porcine sequence with selenium being present as selenocysteine at position 46. The selenenic acid form, which is considered to be the first catalytic intermediate F formed by reaction with hydroperoxide, could not be identified. The second catalytic intermediate G was detected as Se-glutathionylated enzyme. This intermediate is generated in the reverse reaction where the active site selenol interacts with glutathione disulfide (GSSG). According to molecular models, specific binding of reduced glutathione (GSH) and of GSSG is inter alia facilitated by electrostatic attraction of Lys-48 and Lys-125. Polymerization of PHGPx is obtained under oxidizing conditions in the absence of low molecular weight thiols. Analysis of MS spectra revealed that the process is due to a selective reaction of Sec-46 with Cys-148' resulting in linear polymers representing dead-end intermediates (G'). FT Docking of PHGPx molecules allowed reactions of Sec-46 with either Cys-66', Cys-107', Cys-168' or Cys-148', the latter option being most likely as judged by the number of proposed intermediates with reasonable hydrogen bonds, interaction energies and interface areas. We conclude that the same catalytic principles, depending on the conditions, can drive the diverse actions of PHGPx, i.e. hydroperoxide reduction, GSSG reduction, S-derivatization and self-incorporation into biological structures.
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PMID:Versatility of selenium catalysis in PHGPx unraveled by LC/ESI-MS/MS. 1275 87

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

The mRNA levels of three antioxidant genes, Cu/Zn superoxide dismutase (SOD), catalase (CAT) and phospholipid hydroperoxide glutathione peroxidase (GSH-Px), were quantified with real-time qRT-PCR in liver of Atlantic salmon Salmo salar exposed to 80% (normoxia), 105% and 130% O2 saturation for 54 days. The salmon were then translocated and exposed to 90% and 130% O2 saturation for additional 72 days during smoltification. TBARS and vitamin E levels in liver and the levels of oxidized glutathione (GSSG), total glutathione (GSH) and the resulting oxidative stress index (OSI) in blood were quantified as traditional oxidative stress markers. No significant mean normalized expression (MNE) differences of SOD, CAT or GSH-Px were found in liver after hyperoxia exposure at the two sampling times. Significantly decreased OSI was found in smolt exposed to 130% O2 saturation after 126 days (n = 18, P < 0.0001), indicating hyperoxia-induced oxidative stress. No effects were seen on growth, or on the levels of thiobarbituric reactive substances (TBARS) and vitamin E in liver after the exposure experiment. Overall, the mRNA expression of SOD, CAT and GSH-Px in liver related poorly with the hyperoxic exposure regimes, and more knowledge are needed before the expressed levels of these antioxidant genes can be applied as biomarkers of hyperoxia in Atlantic salmon.
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PMID:mRNA expression of antioxidant enzymes (SOD, CAT and GSH-Px) and lipid peroxidative stress in liver of Atlantic salmon (Salmo salar) exposed to hyperoxic water during smoltification. 1610 25

Selenium (Se) is involved in the process of male reproduction. Several studies have been carried out to find the mechanism of Se action through identified selenoproteins. Especially selenoenzyme phospholipid glutathione peroxidase (PHGPx, GPx-4) plays a pivotal role in regulating spermatogenesis. However, the action of selenium is best known as an antioxidant which acts through various selenoproteins viz. glutathione peroxidase, thioredoxin reductase and selenoprotein P. Oxidative stress is currently being considered a leading cause of male infertility. Presently, the involvement of redox active transcription factor, AP1 (Activator protein1) in testicular function was studied. AP1 is redox sensitive and also controls cell proliferation. The effects of Se might be mediated through it. Different Se status - deficient, adequate and excess Se - were generated in male Balb/c mice by feeding yeast based selenium deficient diet and deficient diet supplemented with Se as sodium selenite (0.2 and 1 ppm Se), respectively, for a period of 4 and 8 weeks. Se status was checked by measuring the Se levels and glutathione peroxidase (GSH-Px) activity in testis and liver. The reproductive potential of mice was affected at these changed Se levels. Changes in the activity of superoxide dismutase (SOD), levels of reduced glutathione (GSH) and oxidized glutathione (GSSG) were observed indicating increased oxidative stress at both the levels. Further, changes in the mRNA expression of GSH-Px, gamma-glutamylcysteine synthetase gammaGCS) and Mn superoxide dismutase (MnSOD) were observed. Decrease in cjun and cfos mRNA levels were observed at both the Se status (deficient and excess) which might be responsible for decreased germ cell number, differentiation and reduced fertility observed at the altered Se levels.
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PMID:Role of selenium in regulation of spermatogenesis: involvement of activator protein 1. 1641 Jun 37

The transcript levels of three genes coding for antioxidants, Cu/Zn superoxide dismutase (SOD), catalase and phospholipid hydroperoxide glutathione peroxidase (GSH-Px), and those of two stress proteins, metallothionein (MT) and CYP1A, were examined with real-time quantitative (q) RT-PCR in hepatic tissue of Atlantic cod exposed to 46% (hypoxia), 76% (normoxia) and 145% (hyperoxia) O(2) saturation (tank outlet). To evaluate the oxidative stress state, the levels of total glutathione (tGSH), reduced glutathione (GSH) and oxidized glutathione (GSSG) and subsequently the oxidative stress index (OSI), were determined in the same tissue samples. The transcript level of GSH-Px was significantly upregulated in fish exposed to hyperoxia, and significantly downregulated in fish exposed to hypoxia, compared to the normoxia group. Significant downregulation was also found for SOD and CYP1A transcriptional levels in fish exposed to hypoxia. The transcript levels of catalase and MT did not change in liver of cod exposed to suboptimal oxygen levels. No significant differences were seen between the groups for tGSH, GSH, GSSG or OSI. Prolonged exposure to unfavourable oxygen saturation levels did not alter the OSI, indicating that the antioxidant glutathione system is maintained at an unchanged level in liver of the examined cod.
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PMID:Effects of hypo- and hyperoxia on transcription levels of five stress genes and the glutathione system in liver of Atlantic cod Gadus morhua. 1685 73

A novel cDNA of phospholipid hydroperoxide glutathione peroxidase (PHGPx), which encodes a functional protein capable of complementing the yeast PHGHX-deletion mutant, was recently discovered in radish (Raphanus sativus) and designated as RsPHGPx [Yang X-D, Li W-J, Liu J-Y (2005) Biochim Biophys Acta 1728:199-205]. Sequence alignment suggested that RsPHGPx contains a targeting peptide required for transport to mitochondria, but the experimental evidence for the exact intracellular distribution of RsPHGPx remains to be elucidated. To uncover the cellular localization of plant PHGPx, we first investigated RsPHGPx's intracellular distribution. Western blot analysis of subcellular fractions using the RsPHGPx antiserum clearly indicated the distribution of RsPHGPx in the radish mitochondrial fraction. Furthermore, a construct expressing the RsPHGPx precursor tagged with green fluorescent protein was introduced into tobacco and yeast cells, and the fusion protein was transported into both mitochondria, indicating that RsPHGPx was indeed localized in mitochondria. To explore the biochemical functions of this enzyme, we tested the enzymatic activity of the recombinant RsPHGPx protein. It displayed GSH-dependent peroxidase activity and exhibited the largest affinity to and the highest catalytic efficiency on phosphatidylcholine hydroperoxide, suggesting that phospholipid hydroperoxide is probably the optimum substrate for RsPHGPx. Furthermore, RsPHGPx showed a much higher V (max) value, by two orders of magnitude, than those of all other known plant PHGPxs. Taken together, these results showed evidence for the first time of mitochondrial localization and higher activity of PHGPx in plants and provided a framework for continued studies on the physiological functions of RsPHGPx.
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PMID:A plant mitochondrial phospholipid hydroperoxide glutathione peroxidase: its precise localization and higher enzymatic activity. 1694 66

Analysis of the selenoproteome identified five glutathione peroxidases (GPxs) in mammals: cytosolic GPx (cGPx, GPx1), phospholipid hydroperoxide GPx (PHGPX, GPx4), plasma GPx (pGPX, GPx3), gastrointestinal GPx (GI-GPx, GPx2) and, in humans, GPx6, which is restricted to the olfactory system. GPxs reduce hydroperoxides to the corresponding alcohols by means of glutathione (GSH). They have long been considered to only act as antioxidant enzymes. Increasing evidence, however, suggests that nature has not created redundant GPxs just to detoxify hydroperoxides. cGPx clearly acts as an antioxidant, as convincingly demonstrated in GPx1-knockout mice. PHGPx specifically interferes with NF-kappaB activation by interleukin-1, reduces leukotriene and prostanoid biosynthesis, prevents COX-2 expression, and is indispensable for sperm maturation and embryogenesis. GI-GPx, which is not exclusively expressed in the gastrointestinal system, is upregulated in colon and skin cancers and in certain cultured cancer cells. GI-GPx is a target for Nrf2, and thus is part of the adaptive response by itself, while PHGPx might prevent cancer by interfering with inflammatory pathways. In conclusion, cGPx, PHGPx and GI-GPx have distinct roles, particularly in cellular defence mechanisms. Redox sensing and redox regulation of metabolic events have become attractive paradigms to unravel the specific and in part still enigmatic roles of GPxs.
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PMID:Glutathione peroxidases and redox-regulated transcription factors. 1708 Nov 3

The mechanisms of physiological responses in Atlantic cod, Gadus morhua following vaccination with a heat-killed Vibrio anguillarum were investigated by transcriptome analysis of spleen tissues. Semi-quantitative RT-PCR of several genes involved in immune defense, inflammation, antioxidant defense and glucose transport were determined in vaccinated fish at 1, 3, 7 and 10 days after vaccination (dpv)and compared with sham-injected fish. Transcript levels of the selected genes involved in bacterial defense such as the bactericidal permeability-increasing protein/lipopolysaccharide-binding protein (BPI/LBP), g-type lysozyme and transferrin, were significantly upregulated (P < 0.05) throughout the duration of sampling (1-10 dpv). There was differential expression of the genes involved in antiviral activity, cellular immunity, antioxidant defense and glucose transport, while the pro-inflammatory cytokines remained relatively unchanged in both the vaccinated and sham-vaccinated fish. The expressions of interferon stimulated gene-15 (ISG-15) and interferon regulatory factor-1 (IRF-1), which are involved in viral defense, were significantly enhanced (P < 0.05) after vaccination. Likewise, the transcript levels of the non-specific cytotoxic cell receptor protein-1 (NCCRP-1) and granzyme A/K, which are components of the cell-mediated immunity were upregulated. Among the antioxidants, the transcript levels of catalase and phospholipid hydroperoxide glutathione peroxidase (GSH-Px) significantly increased (P < 0.05) following vaccination, while glucose transporter-4 (GLUT-4) was enhanced among the genes involved in glucose transport. Our results indicate that the spleen of Atlantic cod is able to mount a potent physiological response through enhanced transcription of at least the mentioned genes, upon exposure to a bacterial antigen. These genes work synergistically to protect the fish during subsequent infection.
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PMID:Profiling gene expression in the spleen of Atlantic cod, Gadus morhua upon vaccination with Vibrio anguillarum antigen. 1931 30


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