- 作者: Wen-Chang Chang
- 作者服務機構: Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC
- 中文摘要: --
- 英文摘要: Eicosanoids, which include prostaglandins, thrombox-anes, and leukotrienes, are produced from arachidonicacid by three main pathways in cells, including cyclooxy-genases and lipoxygenases, and cytochrome P450 en-zymes. Accumulated evidence indicates that a certainperoxide tone is required for the initiation of reaction bylipoxygenases and cyclooxygenases.An endogenous in-hibitor of arachidonate oxygenation was suspected inthe cytosolic fraction of human epidermoid carcinomaA431 cells. After a series of studies, the existence of thisinhibitor was confirmed, while it was purified and char-acterized.By amino acid sequence analysis, the inhibitorin A431 cells was subsequently identified as a phospho-lipid hydroperoxide glutathione peroxidase(PHGPx).De-pletion of cellular glutathione in cells by diethyl maleateor by dibuthionine-sulfoximine results in an increase inenzyme activities of 12(S)-lipoxygenase and cyclooxy-genase, suggesting that glutathione-depleting agentsabolish the enzyme activity of PHGPx in cells. Stabletransfectants of A431 cells with overexpression and de-pletion of PHGPx have been constructed,respectively.Reduction of arachidonate metabolism through 12(S)-lipoxygenase and cyclooxygenase 1 and that of the arse-nite-induced generation of reactive oxygen species areobserved in cells overexpressing PHGPx. On the otherhand, enhancement of arachidonate metabolism and thearsenite-induced generation of reactive oxygen speciesis detected in PHGPx-depleted cells. In conclusion,theendogenous inhibitor of arachidonate metabolismpresent in A431 cells is a PHGPx, which plays a function-al role in the down一regulation of arachidonate oxygena-tion catalyzed by 12(S)-lipoxygenase and cyclooxygen-ase 1 through the reduction of the level of intracellularlipid hydroperoxides. The latter acts as the peroxide tonefor arachidonate metabolism in A431 cells.
- 中文關鍵字: --
- 英文關鍵字: Aracjodpmate Oxygenation inhibitor. PHGPx. 12(S)-Lipoxygemase. Cyclooxygenase 1. A431 cells