Lysophosphatidylcholine increases vascular superoxide anion production via protein kinase C activation.
We tested the hypothesis that lysophosphatidylcholine (lyso-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 lyso-PC and 12-O-tetradecanoylphorbol 13-acetate (TPA) were similar. Activation of protein kinase C can stimulate superoxide anion (O2-) production in other tissues, and we found that lyso-PC-treated rabbit aortas produced twofold more O2- than control vessels. Calphostin C, a potent and specific inhibitor of protein kinase C, attenuated O2- production in lyso-PC-treated vessels but had no effect in control vessels. The effect of lyso-PC on O2- 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 lyso-PC. After incubation with calphostin C, EDRF release in response to acetylcholine from lyso-PC-treated donor vessels was restored significantly. Thus, lyso-PC can activate protein kinase C in intact vessels, leading to an increase in O2- production. Activation of protein kinase C by lyso-PC may also play a role in altering the release of EDRF in response to acetylcholine. Increased O2- production in response to lyso-PC may have important consequences in the atherogenic process.
Ohara
Y
Y
Division of Cardiology, Emory University School of Medicine, Atlanta, GA 30322.
Peterson
T E
TE
Zheng
B
B
Kuo
J F
JF
Harrison
D G
DG
D000818:Animals; D001011:Aorta / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D004789:Enzyme Activation; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D009281:Naphthalenes; D011083:Polycyclic Compounds / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011817:Rabbits; D013481:Superoxides / Q000378:metabolism*
D008244:Lysophosphatidylcholines; D009281:Naphthalenes; D011083:Polycyclic Compounds; D013481:Superoxides; D011493:Protein Kinase C; C058819:calphostin C