Selective hydrolysis of plasmalogens in endothelial cells following thrombin stimulation.
Selective hydrolysis of plasmalogens in endothelial cells following thrombin stimulation.
复制标题
凝血酶刺激后内皮细胞中缩醛磷脂的选择性水解。
DOI：
10.1152/ajpcell.1998.275.6.c1498
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
McHowat,J
中科院分区：
文献类型：
--
作者：
Creer,MH;McHowat,J
本研究的特点是凝血酶刺激磷脂酶A2（PLA 2）的活性和溶血磷脂从内皮细胞释放。内皮细胞中的大多数PLA 2活性是膜相关的，Ca 2+非依赖性的，花生四烯酸选择性的。凝血酶孵育增加膜相关的PLA 2的活性使用两个plasmenylcholine和alkylacyl glycerophosphocholine基板在Ca 2+的情况下，没有增加与磷脂酰胆碱基板观察到的活动。磷脂酶A2活性的增加伴随着花生四烯酸和溶浆胆碱（LPlasC）从内皮细胞释放到周围介质中。凝血酶诱导的变化与凝血酶受体定向肽SFLLRNPNDKYEPF刺激复制。用不依赖钙离子的PLA 2抑制剂溴烯醇内酯预处理可阻断凝血酶刺激的PLA 2活性、花生四烯酸和LPlasC释放的增加。蛋白激酶C（PKC）的刺激增加了基础PLA 2活性和LPlasC的产生。凝血酶刺激的PLA 2活性和LPlasC的产生随着PKC的激活而增强，而PKC的下调则完全阻止。因此，凝血酶治疗内皮细胞激活PKC激活的，膜相关的，Ca 2 +-独立的PLA 2，选择性水解花生四烯酸，醚连接的磷脂底物，导致LPlasC和花生四烯酸释放。
The present study was performed to characterize thrombin-stimulated phospholipase A2(PLA2) activity and the resultant release of lysophospholipids from endothelial cells. The majority of PLA2activity in endothelial cells was membrane associated, Ca2+independent, and arachidonate selective. Incubation with thrombin increased membrane-associated PLA2activity using both plasmenylcholine and alkylacyl glycerophosphocholine substrates in the absence of Ca2+, with no increase in activity observed with phosphatidylcholine substrate. The increased PLA2activity was accompanied by arachidonic acid and lysoplasmenylcholine (LPlasC) release from endothelial cells into the surrounding medium. Thrombin-induced changes were duplicated by stimulation with the thrombin-receptor-directed peptide SFLLRNPNDKYEPF. Pretreatment with the Ca2+-independent PLA2inhibitor bromoenol lactone blocked thrombin-stimulated increases in PLA2activity, arachidonic acid, and LPlasC release. Stimulation of protein kinase C (PKC) increased basal PLA2activity and LPlasC production. Thrombin-stimulated PLA2activity and LPlasC production were enhanced with PKC activation and completely prevented with PKC downregulation. Thus thrombin treatment of endothelial cells activates a PKC-activated, membrane-associated, Ca2+-independent PLA2that selectively hydrolyzes arachidonylated, ether-linked phospholipid substrates, resulting in LPlasC and arachidonic acid release.