Myocardial phospholipases A(2) and their membrane substrates.
Many of the adverse sequelae of acute myocardial ischemia result from the degradation of sarcolemmal phospholipid constituents mediated by the activation of intracellular phospholipases. The consequent deleterious changes in sarcolemmal membrane properties precipitate ischemic membrane dysfunction resulting in electrophysiologic alterations and myocytic cell death. In myocardium, the overwhelming majority of phospholipase activity is catalyzed by a novel class of calcium-independent plasmalogen-selective phospholipases A(2) that is rapidly and reversibly activated within minutes of myocardial ischemia. Elucidation of the molecular mechanisms underlying the regulation of these phospholipases A(2) will define novel therapeutic targets that can potentially be pharmacologically manipulated to attenuate the deleterious effects of ischemia and reperfusion on myocardial function.
Director of the Division of Bioorganic Chemistry and Molecular Pharmacology at the Washington University School of Medicine, St. Louis, MO 63110, USA.
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Gross