Cytosolic phospholipase A2-α mediates endothelial cell proliferation and is inactivated by association with the Golgi apparatus

S. P. Herbert, S. Ponnambalam, J. H. Walker

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Arachidonic acid and its metabolites are implicated in regulating endothelial cell proliferation. Cytosolic phospholipase A2-α (cPLA2α) is responsible for receptor-mediated arachidonic acid evolution. We tested the hypothesis that cPLA2α activity is linked to endothelial cell proliferation. The specific cPLA2α inhibitor, pyrrolidine-1, inhibited umbilical vein endothelial cell (HUVEC) proliferation in a dose-dependent manner. Exogenous arachidonic acid addition reversed this inhibitory effect. Inhibition of sPLA2 did not affect HUVEC proliferation. The levels of cPLA2α did not differ between subconfluent and confluent cultures of cells. However, using fluorescence microscopy we observed a novel, confluence-dependent redistribution of cPLA2α to the distal Golgi apparatus in HUVECs. Association of cPLA2α with the Golgi was linked to the proliferative status of HUVECs. When associated with the Golgi apparatus, cPLA 2α activity was seen to be 87% inhibited. Relocation of cPLA2α to the cytoplasm and nucleus, and cPLA 2α enzyme activity were required for cell cycle entry upon mechanical wounding of confluent monolayers. Thus, cPLA2α activity and function in controlling endothelial cell proliferation is regulated by reversible association with the Golgi apparatus. © 2005 by The American Society for Cell Biology.
    Original languageEnglish
    Pages (from-to)3800-3809
    Number of pages9
    JournalMolecular Biology of the Cell
    Volume16
    Issue number8
    DOIs
    Publication statusPublished - Aug 2005

    Keywords

    • Cell Proliferation
    • Cells, Cultured
    • Cytosol/*enzymology
    • Endothelial Cells/*cytology/*enzymology
    • Enzyme Activation
    • Enzyme Inhibitors/pharmacology
    • Golgi Apparatus/*enzymology
    • Group IV Phospholipases A2
    • Humans
    • Ki-67 Antigen/metabolism
    • Phospholipases A/antagonists & inhibitors/*metabolism
    • Phospholipases A2
    • Up-Regulation

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