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)

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

Promoter activation in the expression of phospholipid hydroperoxide glutathione peroxidase (PHGPx) gene in human epidermoid carcinoma A431 cells was studied in the present investigation. Luciferase reporter assays with plasmids carrying a 400 bp of the promoter DNA were performed to analyze the regulatory element in the proximal promoter of human PHGPx gene. Transient transfection with a series of 5'-deletion and internal truncation mutants showed that the 5'-flanking region spanning from -212 to -121 bp was important for the basal expression of PHGPx gene in A431 cells. A region from -170 to -140 bp was protected in DNase I footprinting assays and bound the nuclear proteins in electrophoretic mobility shift assays. This region, denoted FP3, contains the consensus recognition sites for AP-2, CCAAT-box and CRE. The oligonucleotide competitor with the mutation at CCAAT-box could not eliminate the nuclear protein binding in gel-shift assay and the site-directed mutagenesis at the CCAAT-box decreased the luciferase activity of PHGPx promoter for approximate 50% in reporter gene assays. Competition experiments indicate that the binding of nuclear factor to the FP3 region was abolished by oligodeoxyribonucleotide corresponding to NF-Y/CP1 binding site to a greater extent than by those corresponding to sites for CTF/NFI and C/EBP. Taken together, the CCAAT-box in the promoter ranging from -156 to -151 bp, bound to NF-Y/CP1, was essential for the basal expression of human PHGPx gene in A431 cells.
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PMID:The CCAAT-box binding factor NF-Y is required for the expression of phospholipid hydroperoxide glutathione peroxidase in human epidermoid carcinoma A431 cells. 1042 83

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

Eicosanoids, which include prostaglandins, thromboxanes, and leukotrienes, are produced from arachidonic acid by three main pathways in cells, including cyclooxygenases and lipoxygenases, and cytochrome P450 enzymes. Accumulated evidence indicates that a certain peroxide tone is required for the initiation of reaction by lipoxygenases and cyclooxygenases. An endogenous inhibitor of arachidonate oxygenation was suspected in the cytosolic fraction of human epidermoid carcinoma A431 cells. After a series of studies, the existence of this inhibitor was confirmed, while it was purified and characterized. By amino acid sequence analysis, the inhibitor in A431 cells was subsequently identified as a phospholipid hydroperoxide glutathione peroxidase (PHGPx). Depletion of cellular glutathione in cells by diethyl maleate or by dibuthionine-sulfoximine results in an increase in enzyme activities of 12(S)-lipoxygenase and cyclooxygenase, suggesting that glutathione-depleting agents abolish the enzyme activity of PHGPx in cells. Stable transfectants of A431 cells with overexpression and depletion of PHGPx have been constructed, respectively. Reduction of arachidonate metabolism through 12(S)-lipoxygenase and cyclooxygenase 1 and that of the arsenite-induced generation of reactive oxygen species are observed in cells overexpressing PHGPx. On the other hand, enhancement of arachidonate metabolism and the arsenite-induced generation of reactive oxygen species is detected in PHGPx-depleted cells. In conclusion, the endogenous inhibitor of arachidonate metabolism present in A431 cells is a PHGPx, which plays a functional role in the down-regulation of arachidonate oxygenation catalyzed by 12(S)-lipoxygenase and cyclooxygenase 1 through the reduction of the level of intracellular lipid hydroperoxides. The latter acts as the peroxide tone for arachidonate metabolism in A431 cells.
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PMID:Identification of an endogenous inhibitor of arachidonate metabolism in human epidermoid carcinoma A431 cells. 1457 62