Selective plasmalogen substrate utilization by thrombin-stimulated Ca(2+)-independent PLA(2) in cardiomyocytes.
Selective plasmalogen substrate utilization by thrombin-stimulated Ca(2+)-independent PLA(2) in cardiomyocytes.
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DOI：
10.1152/ajpheart.2000.278.6.h1933
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发表时间：
2000-06
期刊：
影响因子：
--
通讯作者：
J. McHowat;M. Creer
中科院分区：
文献类型：
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作者：
J. McHowat;M. Creer
凝血酶刺激兔心室肌细胞激活膜相关的、不依赖于钙离子的磷脂酶A(2)(PLA(2))，该磷脂酶A(2)能够水解胞浆胆碱(胆碱原)、胞浆胆碱(烷基胆碱磷脂)和磷脂酰胆碱底物。为了确定内源性磷脂底物，我们量化了凝血酶刺激对联苯双酯磷脂质量、花生四烯酸和溶血磷脂产生的影响。凝血酶刺激导致花生四烯基化血浆胆碱选择性降低，而花生四烯基磷脂酰胆碱无变化。花生四烯基质膜胆碱的减少伴随着sn-2位含有亚油酸和亚麻酸的质膜胆碱种类的增加。凝血酶刺激后花生四烯醇化胞浆乙醇胺也减少，而花生四烯醇化磷脂酰乙醇胺无明显变化。凝血酶刺激可选择性产生溶血磷脂酰胆碱，但不增加溶血磷脂酰胆碱的含量。没有证据表明溶血磷脂的显著乙酰化形成了血小板激活因子。凝血酶刺激后释放的花生四烯酸迅速氧化为前列环素。因此，凝血酶刺激的非钙依赖的聚乳酸(2)选择性地水解花生四烯基化的纤溶酶原底物，产生溶酶原和前列环素作为主要的生物活性产物。
Thrombin stimulation of rabbit ventricular myocytes activates a membrane-associated, Ca(2+)-independent phospholipase A(2) (PLA(2)) capable of hydrolyzing plasmenylcholine (choline plasmalogen), plasmanylcholine (alkylacyl choline phospholipid), and phosphatidylcholine substrates. To identify the endogenous phospholipid substrates, we quantified the effects of thrombin stimulation on diradyl phospholipid mass and arachidonic acid and lysophospholipid production. Thrombin stimulation resulted in a selective decrease in arachidonylated plasmenylcholine, with no change in arachidonylated phosphatidylcholine. The decrease in arachidonylated plasmenylcholine was accompanied by an increase in plasmenylcholine species containing linoleic and linolenic acids at the sn-2 position. A decrease in arachidonylated plasmenylethanolamine was also observed after thrombin stimulation, with no concomitant change in arachidonylated phosphatidylethanolamine. Thrombin stimulation resulted in the selective production of lysoplasmenylcholine, with no increase in lysophosphatidylcholine content. There was no evidence for significant acetylation of lysophospholipids to form platelet-activating factor. Arachidonic acid released after thrombin stimulation was rapidly oxidized to prostacyclin. Thus thrombin-stimulated Ca(2+)-independent PLA(2) selectively hydrolyzes arachidonylated plasmalogen substrates, resulting in production of lysoplasmalogens and prostacyclin as the principal bioactive products.