Selective hydrolysis of plasmalogens in endothelial cells following thrombin stimulation

Michael H. Creer, Jane McHowat

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)C1498-C1507
JournalAmerican Journal of Physiology - Cell Physiology
Volume275
Issue number6 44-6
DOIs
StatePublished - 1998

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cell Biology

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