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Regulation of cyclooxygenase and 12-lipoxygenase catalysis by phospholipid hydroperoxide glutathione peroxidase in A431 cells
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Abstracts / Prostaglandins & other Lipid Mediators 59 (1999) 1-235
REGULATION OF CYCLOOXYGENASE AND 1ZLIPOXYGENASE CATALYSIS BY PHOSPHOLIPID HYDROPEROXIDE GLUTATHIONE PEROXIDASE IN A43 1 CELLS Ching-Jiunn Chen, Huei-Sheng Huang and Wen-Chang Chang Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, R.O.C.
The eicosanoids, which include the prostaglandins, thromboxanes, and leukotrienes, are produced from arachidonic acid by three main pathways in cells, including cyclooxygenase, lipoxygenase, and cytochrome P450 enzymes. The acctmmlated evidente indicates that hydroperoxides play an important role in the regulation of these oxygenase activities. Two glutathione peroxidases in human epidermoid carcinoma A43 1 cells were identified. One is a common cytosolic glutathione peroxidase 1 (GPxl), and the other is phospholipid hydroperoxide glutathione peroxidase (PHGPx). Regulation of arachidonate metabolism in A43 1 cells by these glutathione peroxidases was studied. Treatment of the crude homogenate of cells with 1 mM iodoacetate at 4 “c for 1 hour to deplete sulfbydryl-groups resulted in increase in the product formation of cyclooxygenase and 1Zlipoxygenase. In order to study the effect of glutathione (GSH) on the catalysis regulation of these oxygenation enzymes, diethyl maleate (DEM) was used to deplete the intracellular GSH. In the present of hydroperoxide 13-HPODE, the enzyme catalysis of cyclooxygenase and 1Zlipoxygenase were signifïcantly increased in the GSHdepleted cells. In inhibition of lZlipoxygenase, PHGPx was more GSH-dependent in comparison with GPx 1. Inhibition of PHGPx activity with antisense oligonucleotide for PHGPx mRNA increased tbe enzyme catalysis of cyclooxygenase and 12-lipoxygenase. Results suggest that catalysis of cyclooxygenase and 1Zlipoxygenase in A43 1 cells was regulated by a redox-reaction marmer, and the glutathione-dependent enzyme PHGPx seems to play an important role in controlling this reaction.
Abstracts / Prostaglandins & other Lipid Mediators 59 (1999) 1-235
REGULATION OF CYCLOOXYGENASE AND 1ZLIPOXYGENASE CATALYSIS BY PHOSPHOLIPID HYDROPEROXIDE GLUTATHIONE PEROXIDASE IN A43 1 CELLS Ching-Jiunn Chen, Huei-Sheng Huang and Wen-Chang Chang Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, R.O.C.
The eicosanoids, which include the prostaglandins, thromboxanes, and leukotrienes, are produced from arachidonic acid by three main pathways in cells, including cyclooxygenase, lipoxygenase, and cytochrome P450 enzymes. The acctmmlated evidente indicates that hydroperoxides play an important role in the regulation of these oxygenase activities. Two glutathione peroxidases in human epidermoid carcinoma A43 1 cells were identified. One is a common cytosolic glutathione peroxidase 1 (GPxl), and the other is phospholipid hydroperoxide glutathione peroxidase (PHGPx). Regulation of arachidonate metabolism in A43 1 cells by these glutathione peroxidases was studied. Treatment of the crude homogenate of cells with 1 mM iodoacetate at 4 “c for 1 hour to deplete sulfbydryl-groups resulted in increase in the product formation of cyclooxygenase and 1Zlipoxygenase. In order to study the effect of glutathione (GSH) on the catalysis regulation of these oxygenation enzymes, diethyl maleate (DEM) was used to deplete the intracellular GSH. In the present of hydroperoxide 13-HPODE, the enzyme catalysis of cyclooxygenase and 1Zlipoxygenase were signifïcantly increased in the GSHdepleted cells. In inhibition of lZlipoxygenase, PHGPx was more GSH-dependent in comparison with GPx 1. Inhibition of PHGPx activity with antisense oligonucleotide for PHGPx mRNA increased tbe enzyme catalysis of cyclooxygenase and 12-lipoxygenase. Results suggest that catalysis of cyclooxygenase and 1Zlipoxygenase in A43 1 cells was regulated by a redox-reaction marmer, and the glutathione-dependent enzyme PHGPx seems to play an important role in controlling this reaction.