Liu S Y, Yu C H, Hays J A, Panagia V, Dhalla N S
St. Boniface General Hospital Research Centre, and Department of Human Anatomy, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Biochim Biophys Acta. 1997 Nov 30;1349(3):264-74. doi: 10.1016/s0005-2760(97)00142-2.
Although lysophosphatidylcholine (lyso-PtdCho) accumulates in the sarcolemmal (SL) membrane and alters its function during myocardial ischemia and diabetic cardiomyopathy, the effects of lyso-PtdCho on SL signalling processes have not yet been investigated. The present study was carried out to examine the actions of lyso-PtdCho on the rat heart SL membrane enzymes involved in the phosphoinositide pathway. Different lyso-PtdCho species (10 to 200 microM) inhibited the activities of both phosphatidylinositol kinase and phosphatidylinositol-4-phosphate kinase in the SL membrane in a concentration-dependent manner. The inhibitory potency of lyso-PtdCho compounds for phosphatidylinositol kinase was lyso-PtdCho plasmalogen > 1-oleoyl-lyso-PtdCho > 1-stearoyl-lyso-PtdCho > 1-palmitoyl-lyso-PtdCho, and that for phosphatidylinositol-4-phosphate kinase was lyso-PtdCho plasmalogen > 1-oleoyl-lyso-PtdCho > 1-palmitoyl-lyso-PtdCho > 1-stearoyl-lyso-PtdCho. The inhibitory effect of lyso-PtdCho on phosphatidylinositol-4-phosphate kinase was greater than that on phosphatidylinositol kinase. Lyso-PtdCho structural analogues, such as phosphatidylcholine, lysophosphatidic acid, lysophosphatidylethanolamine, L-alpha-glycerophosphate, oleate and phosphorylcholine, did not affect the phosphoinositide kinases, suggesting that the intact structure of lyso-PtdCho was required for the inhibition of the kinases. The detrimental action of lyso-PtdCho on PtdIns kinase was potentiated by acidosis. Unlike Ca2+, ATP (0.1 and 4 mM) increased lyso-PtdCho-induced deactivation of the kinases. Both enzyme activities were found to be depressed in the ischemic-reperfused or diabetic hearts. None of the tested lyso-PtdCho species altered phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) hydrolysis by SL phospholipase C. These results indicate that accumulation of lyso-PtdCho in the SL membrane under pathological conditions may diminish the availability of the PtdIns(4,5)P2 substrate for the production of second messengers by receptor-linked phospholipase C.
尽管溶血磷脂酰胆碱（lyso - PtdCho）在心肌缺血和糖尿病心肌病期间会在肌膜（SL）中积累并改变其功能，但lyso - PtdCho对SL信号转导过程的影响尚未得到研究。本研究旨在检测lyso - PtdCho对大鼠心脏SL膜中参与磷脂酰肌醇途径的酶的作用。不同种类的lyso - PtdCho（10至200微摩尔）以浓度依赖的方式抑制了SL膜中磷脂酰肌醇激酶和磷脂酰肌醇 - 4 - 磷酸激酶的活性。lyso - PtdCho化合物对磷脂酰肌醇激酶的抑制效力为溶血磷脂酰胆碱缩醛磷脂> 1 - 油酰基 - lyso - PtdCho> 1 - 硬脂酰基 - lyso - PtdCho> 1 - 棕榈酰基 - lyso - PtdCho，对磷脂酰肌醇 - 4 - 磷酸激酶的抑制效力为溶血磷脂酰胆碱缩醛磷脂> 1 - 油酰基 - lyso - PtdCho> 1 - 棕榈酰基 - lyso - PtdCho> 1 - 硬脂酰基 - lyso - PtdCho。lyso - PtdCho对磷脂酰肌醇 - 4 - 磷酸激酶的抑制作用大于对磷脂酰肌醇激酶的抑制作用。lyso - PtdCho的结构类似物，如磷脂酰胆碱、溶血磷脂酸、溶血磷脂酰乙醇胺、L - α - 甘油磷酸、油酸酯和磷酸胆碱，对磷脂酰肌醇激酶没有影响，这表明lyso - PtdCho的完整结构是抑制这些激酶所必需的。酸中毒会增强lyso - PtdCho对磷脂酰肌醇激酶的有害作用。与钙离子不同，ATP（0.1和4毫摩尔）会增强lyso - PtdCho诱导的激酶失活。在缺血再灌注或糖尿病心脏中，两种酶的活性均降低。所测试的lyso - PtdCho种类均未改变SL磷脂酶C对磷脂酰肌醇 - 4,5 - 二磷酸（PtdIns(4,5)P2）的水解作用。这些结果表明，在病理条件下lyso - PtdCho在SL膜中的积累可能会减少受体连接的磷脂酶C产生第二信使所需的PtdIns(4,5)P2底物的可用性。
