Phospholipid metabolite production in human urothelial cells after protease-activated receptor cleavage
Phospholipid metabolite production in human urothelial cells after protease-activated receptor cleavage
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DOI：
10.1152/ajprenal.00072.2002
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发表时间：
2002-11-01
影响因子：
4.2
通讯作者：
McHowat, J
中科院分区：
文献类型：
--
作者：
Rickard, A;McHowat, J
我们的实验室先前证明，刺激人尿路上皮癌细胞系RT4上的蛋白酶激活受体（PARs）会导致钙非依赖性磷脂酶a (2) （iPLA(2)）的激活，导致花生四烯酸和PGE(2)的释放。在这项研究中，我们研究了PAR在正常人类尿路上皮细胞（HUR）中的激活，从而导致炎症或细胞保护性磷脂代谢物的产生。免疫印迹法证实HUR上存在PAR-1和PAR-2。胰蛋白酶用凝血酶或PAR-2刺激PAR-1导致膜相关iPLA的激活(2)和血小板活化因子、花生四烯酸和PGE的产生(2)。这些反应都被iPLA(2)选择性抑制剂溴烯醇内酯预处理阻断。因此，刺激PAR-1或PAR-2在HUR上导致iPLA(2)催化的磷脂水解，导致代谢物的产生，这些代谢物可能介导炎症或为膀胱提供细胞保护。
Our laboratory demonstrated previously that stimulation of protease-activated receptors (PARs) on the human urothelial carcinoma cell line RT4 results in activation of a calcium-independent phospholipase A(2) (iPLA(2)), leading to arachidonic acid and PGE(2) release. In this study, we have examined PAR activation in normal human urothelial cells (HUR) leading to the production of inflammatory or cytoprotective phospholipid metabolites. The presence of both PAR-1 and PAR-2 on HUR was confirmed by immunoblotting. Stimulation of PAR-1 with thrombin or PAR-2 by tryptase leads to activation of a membrane-associated iPLA(2) and the production of platelet-activating factor, arachidonic acid, and PGE(2). These responses were all blocked by pretreatment with the iPLA(2)-selective inhibitor bromoenol lactone. Thus stimulation of PAR-1 or PAR-2 on HUR leads to iPLA(2)-catalyzed phospholipid hydrolysis, resulting in the production of metabolites that may mediate inflammation or provide cytoprotection to the bladder.