Selective hydrolysis of plasmalogens in endothelial cells following thrombin stimulation

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Abstract
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.

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