LYSOPHOSPHATIDYLCHOLINE INCREASES VASCULAR SUPEROXIDE ANION PRODUCTION VIA PROTEIN-KINASE-C ACTIVATION
LYSOPHOSPHATIDYLCHOLINE INCREASES VASCULAR SUPEROXIDE ANION PRODUCTION VIA PROTEIN-KINASE-C ACTIVATION
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DOI：
10.1161/01.atv.14.6.1007
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发表时间：
1994-06-01
期刊：
影响因子：
--
通讯作者：
HARRISON, DG
中科院分区：
文献类型：
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作者：
OHARA, Y;PETERSON, TE;HARRISON, DG
我们测试的假设，溶血磷脂酰胆碱（裂解PC）可以激活蛋白激酶C在完整的血管段，并试图检查这种激活的生理后果。在兔主动脉节段中，裂解-PC和12-O-十四酰佛波醇13-乙酸酯（TPA）刺激的双向电泳测定的蛋白磷酸化模式相似。蛋白激酶C的激活可以刺激其他组织中超氧阴离子（O-2（-））的产生，我们发现裂解PC处理的兔动脉产生的O-2（-）是对照血管的两倍。Calphostin C是一种有效的特异性蛋白激酶C抑制剂，可减弱裂解PC处理血管中O-2（-）的产生，但对对照血管无影响。用TPA模拟裂解PC对O-2（-）产生的影响。在单独的生物测定研究中，释放的内皮源性血管舒张因子（EDRF）定量检测血管的反应显着受损后，供体兔主动脉段暴露于裂解PC。与calphostin C孵育后，EDRF释放响应乙酰胆碱从裂解PC处理的供体血管显着恢复。因此，裂解PC可以激活完整血管中的蛋白激酶C，导致O-2（-）产生增加。裂解-PC激活蛋白激酶C也可能在改变响应乙酰胆碱的EDRF释放中起作用。溶血-PC引起的O-2（-）产生增加可能在致动脉粥样硬化过程中具有重要作用。
We tested the hypothesis that lysophosphatidylcholine (lyse-PC) could activate protein kinase C in intact vascular segments and sought to examine some of the physiological consequences of this activation. In segments of rabbit aorta, the patterns of protein phosphorylation determined by two-dimensional electrophoresis stimulated by lyse-PC and 12-O-tetradecanoylphorbol 13-acetate (TPA) were similar. Activation of protein kinase C can stimulate superoxide anion (O-2(-)) production in other tissues, and we found that lyse-PC-treated rabbit aortas produced twofold more O-2(-) than control vessels. Calphostin C, a potent and specific inhibitor of protein kinase C, attenuated O-2(-) production in lyse-PC-treated vessels but had no effect in control vessels. The effect of lyse-PC on O-2(-) production was mimicked by TPA. In separate bioassay studies, release of the endothelium-derived vascular relaxing factor (EDRF) quantified by the response of detector vessels was markedly impaired after exposure of donor rabbit aortic segments to lyse-PC. After incubation with calphostin C, EDRF release in response to acetylcholine from lyse-PC-treated donor vessels was restored significantly. Thus, lyse-PC can activate protein kinase C in intact vessels, leading to an increase in O-2(-) production. Activation of protein kinase C by lyse-PC may also play a role in altering the release of EDRF in response to acetylcholine. Increased O-2(-) production in response to lyso-PC may have important consequences in the atherogenic process.