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

Using a conditional life or death screen in yeast, we have isolated a tomato (Lycopersicon esculentum) gene encoding a phospholipid hydroperoxide glutathione peroxidase (LePHGPx). The protein displayed reduced glutathione-dependent phospholipid hydroperoxide peroxidase activity, but differs from counterpart mammalian enzymes that instead contain an active seleno-Cys. LePHGPx functioned as a cytoprotector in yeast (Saccharomyces cerevisiae), preventing Bax, hydrogen peroxide, and heat stress induced cell death, while also delaying yeast senescence. When tobacco (Nicotiana tabacum) leaves were exposed to lethal levels of salt and heat stress, features associated with mammalian apoptosis were observed. Importantly, transient expression of LePHGPx protected tobacco leaves from salt and heat stress and suppressed the apoptotic-like features. As has been reported, conditional expression of Bax was lethal in tobacco, resulting in tissue collapse and membrane permeability to Evans blue. When LePHGPx was coexpressed with Bax, little cell death and no vital staining were observed. Moreover, stable expression of LePHGPx in tobacco conferred protection against the fungal phytopathogen Botrytis cinerea. Taken together, our data indicated that LePHGPx can protect plant tissue from a variety of stresses. Moreover, functional screens in yeast are a viable tool for the identification of plant genes that regulate cell death.
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PMID:Tomato phospholipid hydroperoxide glutathione peroxidase inhibits cell death induced by Bax and oxidative stresses in yeast and plants. 1523 16

We have established several focal adhesion kinase (FAK) cDNA-transfected HL-60 (HL-60/FAK) cells which were highly resistant to oxidative stress-induced apoptosis. To identify target genes that are involved in HL-60/FAK cells, we performed cDNA microarray screening using apoptosis-chip. There, we identified the decrease of glutathione peroxidase (GPx). This result prompted us to investigate the changes of antioxidant enzymes. Here, we demonstrate that lipid peroxidation was suppressed after treatment with hydrogen peroxide in HL-60/FAK cells but not vector-transfected HL-60 (HL-60/Vect) cells. Furthermore, we demonstrate that HL-60/FAK cells have higher basal reactive oxygen species (ROS) levels than the parental HL-60 or HL-60/Vect cells, while ROS accumulation by hydrogen peroxide treatment was almost the same in these cells. Basal activity and mRNA expression of antioxidant enzymes, particularly of GSH reductase (GRe), phospholipid hydroperoxide glutathione peroxidase (PHGPx) were markedly elevated in HL-60/FAK cells. In contrast, GPx and catalase levels were decreased in HL-60/FAK cells. Further, a Src family kinases inhibitor, PP2, suppressed GRe and PHGPx mRNA by inactivation of FAK and c-Src in HL-60/FAK cells. These results suggest that FAK upregulates antioxidant enzymes and suppresses lipid peroxidation, resulting in the anti-apoptotic state for oxidative stress.
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PMID:Induction of antioxidant enzymes by FAK in a human leukemic cell line, HL-60. 1523 16

A dramatic reduction in the expression of a novel phospholipid hydroperoxide glutathione peroxidase (PHGPx), which incorporates cysteine instead of selenocysteine in the conserved catalytic motif was observed in a microarray analysis using cDNAs amplified from mRNA of Brca1-null mouse embryonic fibroblasts. This non-selenocysteine PHGPx named NPGPx is a cytoplasmic protein with molecular mass of approximately 22 kDa and has little detectable glutathione peroxidase activity in vitro. Ectopic expression of NPGPx in Brca1-null cells that were sensitive to oxidative stress induced by hydrogen peroxide conferred a similar resistance level to that of the wild-type cells, suggesting the importance of this protein in reducing oxidative stress. Expression of NPGPx was found in many tissues, including developing mammary gland. However, the majority of breast cancer cell lines studied (11 of 12) expressed very low or undetectable levels of NPGPx irrespective of BRCA1 status. Re-expression of NPGPx in breast cancer lines, MCF-7 and HCC1937, which have very little or no endogenous NPGPx, induced resistance to eicosapentaenoic acid (an omega-3 type of polyunsaturated fatty acid)-mediated cell death. Conversely, inhibition of the expression of NPGPx by the specific small interfering RNA in HS578T breast cancer cells that originally express substantial amounts of endogenous NPGPx increased their sensitivity to eicosapentaenoic acid-mediated cell death. Thus, NPGPx plays an essential role in breast cancer cells in alleviating oxidative stress generated from polyunsaturated fatty acid metabolism.
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PMID:Identification of a novel putative non-selenocysteine containing phospholipid hydroperoxide glutathione peroxidase (NPGPx) essential for alleviating oxidative stress generated from polyunsaturated fatty acids in breast cancer cells. 1529 5

The oviduct plays a crucial role in mammalian reproduction by providing an optimal environment for the final maturation and transport of gametes, fertilization, and early embryonic development. It is now recognized that these reproductive events in vitro can be either negatively or positively affected by reactive oxygen species such as hydrogen peroxide and lipid hydroperoxides. In the current study, we analyzed the expression of the phospholipid hydroperoxide glutathione peroxidase (PHGPx or GPx-4), a selenoenzyme that directly reduces membrane-bound lipid hydroperoxides in the bovine oviduct. Using in situ hybridization, we demonstrated that GPx-4 expression is almost restricted to the oviductal luminal epithelium in contrast to GPx-1, which is widely distributed, and GPx-2 and -3, which are mainly detected in the epithelial cells and lamina propria. Interestingly, real-time quantitative RT-PCR analysis showed that GPx-4 expression was highest during the follicular and postovulatory phases. In addition, GPx-4 expression was highest in the isthmus proximal to the dominant follicle during the follicular stage and remained high during the postovulatory period. This increased in expression of GPx-4 corresponded to increased GPx-4 enzymatic activity. Based on intrauterine infusion of estradiol, we determined that the increase in expression and activity of GPx-4 is estrogen mediated. This work clearly demonstrates that GPx-4 gene expression is influenced by the proximity of the dominant follicle in the oviduct in vivo. We propose that GPx-4 has an important role in the physiological control of peroxide tone in the bordering cells of the oviductal lumen.
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PMID:Estrogen selectively up-regulates the phospholipid hydroperoxide glutathione peroxidase in the oviducts. 1574 55

Mitochondria are major compartments in cells responsible for generating reactive oxygen species, which can cause the development of diabetes, Parkinson's disease and premature aging. Antioxidant systems in mitochondria are important for the prevention of diseases and reduction in the speed of aging. We investigated whether the reactive oxygen species generated in mitochondria induced the expression of metallothionein as an antioxidant. We compared the expression level of metallothionein mRNA in mitochondrial phospholipid hydroperoxide glutathione peroxidase (PHGPx)-overexpressed (PHGPx-ov) cells with that in control cells. These cells were treated with respiratory inhibitors, including rotenone and 2, 4-dinitrophenol; under these conditions, the PHGPx-ov cells were more resistant to cell death than the control cells. In addition, the intracellular reactive oxygen species level that was induced by these inhibitors was lower in PHGPx-ov cells than in control cells. This indicates that PHGPx degrades the membrane phospholipid hydroperoxide that is formed via the reactive oxygen species generated in mitochondria. The enhanced expression of metallothionein-I and metallothionein-II mRNA in rotenone-treated control cells was significantly decreased in rotenone-treated PHGPx-ov cells, suggesting that the hydrogen peroxide that is formed by superoxide anions generated in mitochondria diffuse into the cytosol and induce metallothionein mRNA expression. Conversely, the expression of manganese-superoxide dismutase (Mn-SOD) mRNA, which is localized in mitochondria, was not correlated with the intracellular reactive oxygen species level that was induced by rotenone treatment. These results suggest that metallothionein expression is sensitively and strictly regulated by the oxidative state that is induced by mitochondrial respiration.
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PMID:Enhanced metallothionein gene expression induced by mitochondrial oxidative stress is reduced in phospholipid hydroperoxide glutathione peroxidase-overexpressed cells. 1981 60

Overexpression of phospholipid hydroperoxide glutathione peroxidase (PHGPx) genes has been reported to play an important role in protecting host cells from oxidative injury in several model systems. A radish phospholipid hydroperoxide glutathione peroxidase (RsPHGPx) known to have high catalytic activity was applied to mouse 3T3 fibroblasts to determine the protective effects of PHGPx against oxidative injury triggered by hydroperoxides such as hydrogen peroxide (H(2)O(2)), tert-butyl hydroperoxide (t-BHP) and phosphatidylcholine hydroperoxide (PCOOH). We observed that preincubation of cells with RsPHGPx significantly increased cell viability, reduced levels of malondialdehyde (MDA), inhibited generation of reactive oxygen species (ROS), and maintained natural cell shapes after treatment with H(2)O(2), t-BHP or PCOOH, indicating that the exogenous RsPHGPx can act as an effective hydroperoxide-scavenger and may also protect target cells from oxidative damage. These results suggest the possibility for use of RsPHGPx as a therapeutic protectant.
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PMID:Radish phospholipid hydroperoxide glutathione peroxidase provides protection against hydroperoxide-mediated injury in mouse 3T3 fibroblasts. 1987 9

Mitochondrial dysfunction is a contributor to diabetic cardiomyopathy. Previously, we observed proteomic decrements within the inner mitochondrial membrane (IMM) and matrix of diabetic cardiac interfibrillar mitochondria (IFM) correlating with dysfunctional mitochondrial protein import. The goal of this study was to determine whether overexpression of mitochondria phospholipid hydroperoxide glutathione peroxidase 4 (mPHGPx), an antioxidant enzyme capable of scavenging membrane-associated lipid peroxides in the IMM, could reverse proteomic alterations, dysfunctional protein import, and ultimately, mitochondrial dysfunction associated with the diabetic heart. MPHGPx transgenic mice and controls were made diabetic by multiple low-dose streptozotocin injections and examined after 5 wk of hyperglycemia. Five weeks after hyperglycemia onset, in vivo analysis of cardiac contractile function revealed decreased ejection fraction and fractional shortening in diabetic hearts that was reversed with mPHGPx overexpression. MPHGPx overexpression increased electron transport chain function while attenuating hydrogen peroxide production and lipid peroxidation in diabetic mPHGPx IFM. MPHGPx overexpression lessened proteomic loss observed in diabetic IFM. Posttranslational modifications, including oxidations and deamidations, were attenuated in diabetic IFM with mPHGPx overexpression. Mitochondrial protein import dysfunction in diabetic IFM was reversed with mPHGPx overexpression correlating with protein import constituent preservation. Ingenuity Pathway Analyses indicated that oxidative phosphorylation, tricarboxylic acid cycle, and fatty acid oxidation processes most influenced in diabetic IFM were preserved by mPHGPx overexpression. Specific mitochondrial networks preserved included complex I and II, mitochondrial ultrastructure, and mitochondrial protein import. These results indicate that mPHGPx overexpression can preserve the mitochondrial proteome and provide cardioprotective benefits to the diabetic heart.
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PMID:Reversal of mitochondrial proteomic loss in Type 1 diabetic heart with overexpression of phospholipid hydroperoxide glutathione peroxidase. 2340 27


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