Arachidonic acid release by cPLA2 may be causally related to NO-induced apoptosis in vascular smooth muscle cells.
Apoptosis has been shown to occur in vascular smooth muscle cells during the development of atherosclerosis. In order to investigate the possible role of arachidonic acid during apoptosis in vascular smooth muscle, we induced apoptosis in cultured rat aortal smooth muscle cells (SMCs) by treatment with either UV (ultraviolet) radiation, tumor necrosis factor-alpha (TNF-alpha) or NO donor drugs (sodium nitroprusside, or S-nitroso-N-acetyl-D-penicillamine, SNAP). Apoptosis was detected by either DNA fragmentation analysis or by TUNEL analysis. UV radiation, TNF-alpha and NO were observed to stimulate apoptosis in the cells as well as to stimulate arachidonate release from the cells. NO also increased levels of cPLA2 in the cells, which is an enzyme that is frequently activated in cells that release arachidonate. These agents stimulated arachidonate release somewhat earlier than they stimulated apoptosis in the cells. The inhibition of cPLA2 by arachidonyl trifluoromethyl ketone (AACOCF3) also led to the inhibition of arachidonate release from the cells as well as the inhibition of nitroprusside stimulated apoptosis. Arachidonic acid itself could induce apoptosis in the cultured cells. These observations provide evidence that arachidonate may be involved in apoptosis in vascular smooth muscle.
Pilane
Cyril M
CM
Department of Pharmacology and Physiology, MCP-Hahnemann University, Philadelphia, Pennsylvania 19102, USA.
LaBelle
Edward F
EF
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D016718:Arachidonic Acid / Q000378:metabolism* / Q000494:pharmacology; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D054513:Group IV Phospholipases A2; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology* / Q000528:radiation effects; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D014466:Ultraviolet Rays
D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D016718:Arachidonic Acid; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D010741:Phospholipases A; D054513:Group IV Phospholipases A2