cPLA2 activator peptide, PLAP, increases arachidonic acid release and apoptosis of vascular smooth muscle cells.
Apoptosis of vascular smooth muscle cells (VSMCs) has recently drawn a lot of interest in various laboratories due to its importance in atherogenesis. We have shown previously that nitric-oxide (NO) can induce apoptosis of VSMCs and that the NO-induced apoptosis is accompanied by an increase in arachidonic acid release via cytoplasmic Ca(2+)-dependent phospholipase A(2) (cPLA(2)). We have demonstrated here that NO-induced activation of cPLA(2) leading to increased arachidonic acid release can be mimicked via direct activation of cPLA(2) with a cPLA(2) activator peptide, PLAP. The PLAP induced arachidonic acid release and apoptosis is inhibitable by a cPLA(2)-specific inhibitor, AACOCF(3), indicating the direct involvement of cPLA(2). In this study, activation of cPLA(2) appears to be preceded by activation and binding by PLAP indicating that the cPLA(2) functions are mediated via PLAP.
Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, USA.
Cyril M
CM
Pilane
Edward F
EF
LaBelle
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D016718:Arachidonic Acid / Q000378:metabolism*; D002470:Cell Survival; D002478:Cells, Cultured; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D019301:Oleic Acid / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D051381:Rats
D004791:Enzyme Inhibitors; D011506:Proteins; C055324:phospholipase A2-activating protein; D016718:Arachidonic Acid; D019301:Oleic Acid; D009569:Nitric Oxide; D010741:Phospholipases A