Key result
Thrombin treatment of endothelial cells activates a PKC-activated, Ca2+-independent PLA2 that selectively hydrolyzes ether-linked phospholipids, releasing LPlasC and arachidonic acid.
Thrombin stimulates endothelial cells to activate a specific Ca2+-independent PLA2 via PKC, leading to the release of arachidonic acid and lysoplasmenylcholine.
Supports thrombin-PKC-iPLA2 signaling in endothelial lipid release; leaves open in vivo relevance and clinical translation.
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 PLA2 activity in endothelial cells was membrane associated, Ca2+ independent, and arachidonate selective. Incubation with thrombin increased membrane-associated PLA2 activity using both plasmenylcholine and alkylacyl glycerophosphocholine substrates in the absence of Ca2+, with no increase in activity observed with phosphatidylcholine substrate. The increased PLA2 activity 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 PLA2 inhibitor bromoenol lactone blocked thrombin-stimulated increases in PLA2 activity, arachidonic acid, and LPlasC release. Stimulation of protein kinase C (PKC) increased basal PLA2 activity and LPlasC production. Thrombin-stimulated PLA2 activity 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 PLA2 that selectively hydrolyzes arachidonylated, ether-linked phospholipid substrates, resulting in LPlasC and arachidonic acid release.
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Creer et al. (1998) studied this question. Thrombin stimulation was evaluated on PLA2 activity and release of lysophospholipids and arachidonic acid. Thrombin treatment of endothelial cells activates a PKC-activated, Ca2+-independent PLA2 that selectively hydrolyzes ether-linked phospholipids, releasing LPlasC and arachidonic acid.
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