Selective plasmalogen substrate utilization by thrombin-stimulated Ca(2+)-independent PLA(2) in cardiomyocytes.
Thrombin stimulation of rabbit ventricular myocytes activates a membrane-associated, Ca(2+)-independent phospholipase A(2) (PLA(2)) capable of hydrolyzing plasmenylcholine (choline plasmalogen), plasmanylcholine (alkylacyl choline phospholipid), and phosphatidylcholine substrates. To identify the endogenous phospholipid substrates, we quantified the effects of thrombin stimulation on diradyl phospholipid mass and arachidonic acid and lysophospholipid production. Thrombin stimulation resulted in a selective decrease in arachidonylated plasmenylcholine, with no change in arachidonylated phosphatidylcholine. The decrease in arachidonylated plasmenylcholine was accompanied by an increase in plasmenylcholine species containing linoleic and linolenic acids at the sn-2 position. A decrease in arachidonylated plasmenylethanolamine was also observed after thrombin stimulation, with no concomitant change in arachidonylated phosphatidylethanolamine. Thrombin stimulation resulted in the selective production of lysoplasmenylcholine, with no increase in lysophosphatidylcholine content. There was no evidence for significant acetylation of lysophospholipids to form platelet-activating factor. Arachidonic acid released after thrombin stimulation was rapidly oxidized to prostacyclin. Thus thrombin-stimulated Ca(2+)-independent PLA(2) selectively hydrolyzes arachidonylated plasmalogen substrates, resulting in production of lysoplasmalogens and prostacyclin as the principal bioactive products.
McHowat
J
J
Department of Pathology, St. Louis University School of Medicine, Missouri 63104, USA. mchowatj@slucare1.sluh.edu
Creer
M H
MH
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000502:physiology; D011464:Epoprostenol / Q000096:biosynthesis; D005260:Female; D019787:Linoleic Acid / Q000032:analysis; D008244:Lysophosphatidylcholines / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010084:Oxidation-Reduction; D010741:Phospholipases A / Q000378:metabolism*; D010955:Plasmalogens / Q000737:chemistry / Q000378:metabolism*; D011817:Rabbits; D013379:Substrate Specificity; D013917:Thrombin / Q000494:pharmacology*; D017962:alpha-Linolenic Acid / Q000032:analysis
D008244:Lysophosphatidylcholines; D010955:Plasmalogens; C032459:choline plasmalogens; C020791:phosphatidal ethanolamines; D017962:alpha-Linolenic Acid; D016718:Arachidonic Acid; D019787:Linoleic Acid; D011464:Epoprostenol; D010741:Phospholipases A; D013917:Thrombin; D002118:Calcium