在人鳞癌A431细胞中,表皮生长因子促进前列腺素E2的产生需要胞质磷脂酶A2和环氧合酶2的协同激活

Takashi Sato, Hideki Nakajima, Kazumi Fujio, Yo Mori
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引用次数: 55

摘要

我们证实了表皮生长因子(EGF)对人鳞状癌A431细胞中PGE2生成的影响。EGF刺激细胞2小时可增加PGE2的生成,并在10小时内达到最大值。EGF还可以增加花生四烯酸(AA)的释放,使磷脂酶A2 (PLA2)活性增加1.7倍。4-溴苯酰溴降低了诱导的PLA2活性,而二硫苏糖醇则没有,这表明egf诱导的AA释放是由于细胞质PLA2 (cPLA2)活性的增加。另一方面,egf处理后2 h内,环氧合酶(COX)活性增加1.6倍,环己亚胺抑制了COX的诱导活性。此外,Northern blot分析显示,egf处理后COX-2 mRNA水平升高,而未处理的细胞中未检测到COX-2 mRNA,表明egf诱导的COX活性是由于COX-2的产生增加所致。这些结果表明,EGF不仅通过增加A431细胞中cPLA2的活性,还通过增加COX-2的产生来增加PGE2的产生。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Enhancement of Prostaglandin E2 Production by Epidermal Growth Factor Requires the Coordinate Activation of Cytosolic Phospholipase A2 and Cyclooxygenase 2 in Human Squamous Carcinoma A431 Cells

We demonstrated the effect of epidermal growth factor (EGF) on the production of PGE2 in human squamous carcinoma A431 cells. The production of PGE2 was increased by stimulating the cells with EGF for 2 h and reached a maximum for 10 h. EGF was also found to augment the release of arachidonic acid (AA) following the increase in phospholipase A2 (PLA2) activity (1.7-fold). The induced PLA2 activity was diminished by 4-bromophenacyl bromide, but not by dithiothreitol, indicating that the EGF-induced release of AA was due to the increase in the activity of cytosolic PLA2 (cPLA2). On the other hand, cyclooxygenase (COX) activity was increased (1.6-fold) within 2 h after the EGF-treatment and the induced activity was inhibited by cycloheximide. In addition, Northern blot analysis showed that the level of COX-2 mRNA was increased by the EGF-treatment, whereas no COX-2 mRNA was detected in the untreated cells, indicating that the EGF-induced COX activity was resulted from the increase in the production of COX-2. These results suggest that EGF augments the production of PGE2 by increasing not only the activity of cPLA2 but also the production of COX-2 in A431 cells.

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