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磷脂氢过氧化物谷胱甘肽过氧化物酶对A431细胞中环氧化酶和12-脂氧合酶催化作用的调节

Regulation of cyclooxygenase and 12-lipoxygenase catalysis by phospholipid hydroperoxide glutathione peroxidase in A431 cells.

作者信息

Chen C J, Huang H S, Lin S B, Chang W C

机构信息

Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China.

出版信息

Prostaglandins Leukot Essent Fatty Acids. 2000 Apr;62(4):261-8. doi: 10.1054/plef.2000.0153.

DOI:10.1054/plef.2000.0153
PMID:10882192
Abstract

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.

摘要

研究了磷脂氢过氧化物谷胱甘肽过氧化物酶(PHGPx)和胞质谷胱甘肽过氧化物酶(GPx1)对人表皮样癌A431细胞中花生四烯酸代谢的调节作用。为了研究还原型谷胱甘肽(GSH)对这些加氧酶催化调节的影响,使用马来酸二乙酯耗尽细胞内的GSH。在13-氢过氧十八碳二烯酸存在的情况下,GSH耗尽的细胞中环氧合酶和12-脂氧合酶的酶促催化作用显著增加。就对12-脂氧合酶的抑制作用而言,PHGPx比GPx1对GSH浓度更敏感。用PHGPx mRNA的反义寡核苷酸处理细胞抑制PHGPx活性,增加了环氧合酶和12-脂氧合酶的酶促催化作用。总之,结果表明A431细胞中环氧合酶和12-脂氧合酶的催化作用受氧化还原反应调节,并且PHGPx似乎在控制这些反应中起重要作用。

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