Calcium-independent phospholipase A2 is regulated by a novel protein kinase C in human coronary artery endothelial cells

Maureen C. Meyer, Pamela J. Kell, Michael H. Creer, Jane McHowat

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34 Scopus citations


We demonstrated previously that thrombin stimulation of endothelial cells activates a membrane-associated, Ca2+-independent phospholipase A2 (iPLA2) that selectively hydrolyzes arachidonylated plasmalogen phospholipids. We report that incubation of human coronary artery endothelial cells (HCAEC) with phorbol 12-myristate 13-acetate (PMA) to activate protein kinase C (PKC) resulted in hydrolysis of cellular phospholipids similar to that observed with thrombin stimulation (0.05 IU/ml; 10 min). Thrombin stimulation resulted in a decrease in arachidonylated plasmenylcholine (2.7 ± 0.1 vs. 5.3 ± 0.4 nmol PO4/mg of protein) and plasmenylethanolamine (7.5 ± 1.0 vs. 12.0 ± 0.9 nmol PO 4/mg of protein). Incubation with PMA resulted in decreases in arachidonylated plasmenylcholine (3.2 ± 0.3 nmol PO4/mg of protein) and plasmenylethanolamine (6.0 ± 1.0 nmol PO4/g of protein). Incubation of HCAEC with the selective iPLA2 inhibitor bromoenol lactone (5 mM; 10 min) inhibited accelerated plasmalogen phospholipid hydrolysis in response to both PMA and thrombin stimulation. Incubation of HCAEC with PMA (100 nM; 5 min) resulted in increased arachidonic acid release (7.1 ± 0.3 vs. 1.1 ± 0.1%) and increased production of lysoplasmenylcholine (1.4 ± 0.2 vs. 0.6 ± 0.1 nmol PO 4/mg of protein), similar to the responses observed with thrombin stimulation. Downregulation of PKC by prolonged exposure to PMA (100 nM; 24 h) completely inhibited thrombin-stimulated increases in arachidonic acid release (7.1 ± 0.6 to 0.5 ± 0.1%) and lysoplasmenylcholine production (2.0 ± 0.1 to 0.2 ± 0.1 nmol PO4/mg of protein). These data suggest that PKC activates iPLA2 in HCAEC, leading to accelerated plasmalogen phospholipid hydrolysis and increased phospholipid metabolite production.

Original languageEnglish (US)
Pages (from-to)C475-C482
JournalAmerican Journal of Physiology - Cell Physiology
Issue number2 57-2
StatePublished - Feb 2005

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cell Biology


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