The confluence-dependent interaction of cytosolic phospholipase A 2-α with annexin A1 regulates endothelial cell prostaglandin E2 generation

Shane P. Herbert, Adam F. Odell, Sreenivasan Ponnambalam, John H. Walker

    Research output: Contribution to journalArticlepeer-review


    The regulated generation of prostaglandins from endothelial cells is critical to vascular function. Here we identify a novel mechanism for the regulation of endothelial cell prostaglandin generation. Cytosolic phospholipase A2-α(cPLA2α) cleaves phospholipids in a Ca2+-dependent manner to yield free arachidonic acid and lysophospholipid. Arachidonic acid is then converted into prostaglandins by the action of cyclooxygenase enzymes and downstream synthases. By previously undefined mechanisms, nonconfluent endothelial cells generate greater levels of prostaglandins than confluent cells. Here we demonstrate that Ca 2+-independent association of cPLA2α with the Golgi apparatus of confluent endothelial cells correlates with decreased prostaglandin synthesis. Golgi association blocks arachidonic acid release and prevents functional coupling between cPLA2α and COX-mediated prostaglandin synthesis. When inactivated at the Golgi apparatus of confluent endothelial cells, cPLA2α is associated with the phospholipid-binding protein annexin A1. Furthermore, the siRNA-mediated knockdown of endogenous annexin A1 significantly reverses the inhibitory effect of confluence on endothelial cell prostaglandin generation. Thus the confluence-dependent interaction of cPLA2α and annexin A1 at the Golgiacts as a novel moleculars witch controlling cPLA2α activity and endothelial cell prostaglandin generation. © 2007 by The American Society for Biochemistry and Molecular Biology, Inc.
    Original languageEnglish
    Pages (from-to)34469-34478
    Number of pages9
    JournalJournal of Biological Chemistry
    Issue number47
    Publication statusPublished - 23 Nov 2007


    • Annexin A1/antagonists & inhibitors/*metabolism
    • Arachidonic Acid/metabolism
    • Calcium/metabolism
    • Cells, Cultured
    • Dinoprostone/*biosynthesis
    • Endothelial Cells/cytology/*enzymology
    • Enzyme Activation/drug effects
    • Golgi Apparatus/*enzymology
    • Group IV Phospholipases A2/*metabolism
    • Humans
    • Lysophospholipids/metabolism
    • Prostaglandin-Endoperoxide Synthases/metabolism
    • RNA, Small Interfering/pharmacology


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