LYSOPHOSPHATIDYLCHOLINE INCREASES VASCULAR SUPEROXIDE ANION PRODUCTION VIA PROTEIN-KINASE-C ACTIVATION

We tested the hypothesis that lysophosphatidylcholine (lyse-PC) could activate protein kinase C in intact vascular segments and sought to ex amine some of the physiological consequences of this activation. In se gments of rabbit aorta, the patterns of protein phosphorylation determ ined by two-dimensional electrophoresis stimulated by lyse-PC and 12-O -tetradecanoylphorbol 13-acetate (TPA) were similar. Activation of pro tein kinase C can stimulate superoxide anion (O-2(-)) production in ot her tissues, and we found that lyse-PC-treated rabbit aortas produced twofold more O-2(-) than control vessels. Calphostin C, a potent and s pecific inhibitor of protein kinase C, attenuated O-2(-) production in lyse-PC-treated vessels but had no effect in control vessels. The eff ect of lyse-PC on O-2(-) production was mimicked by TPA. In separate b ioassay studies, release of the endothelium-derived vascular relaxing factor (EDRF) quantified by the response of detector vessels was marke dly impaired after exposure of donor rabbit aortic segments to lyse-PC . After incubation with calphostin C, EDRF release in response to acet ylcholine from lyse-PC-treated donor vessels was restored significantl y. Thus, lyse-PC can activate protein kinase C in intact vessels, lead ing 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 r esponse to acetylcholine. Increased O-2(-) production in response to l yso-PC may have important consequences in the atherogenic process.