Plasmalogens, phospholipases A(2), and signal transduction

Several lines of evidence indicate that the breakdown of plasmalogens in neural membranes during neurodegenerative diseases is a receptor-mediated process catalyzed by a plasmalogen-selective phospholipase A(2). This enzyme has recently been purified from bovine brain. It does not require Ca2+ and is localized in cytosol. It has a molecular mass of 39 kDa and is strongly inhibited by glycosaminoglycans, with the pattern of inhibition being heparan sulfate > hyaluronic acid > chondroitin sulfate > heparin. This plasmalogen-selective phospholipase A(2) is also inhibited by gangliosides and sialoglycoproteins. Substrate specificity and the effects of metal ions, detergents and inhibitors suggest that this phospholipase A, is different from the well-known 85 kDa Ca2+-dependent cytosolic phospholipase A(2) that has recently been cloned and is not plasmalogen-selective. The plasmalogen-selective phospholipase A(2) may be regulated by glycosaminoglycans and sialoglycoconjugates and may be involved in the regulation of K+ channels. This enzyme, which plays a major role in the release of fatty acids during ischemic injury and reperfusion, shows promise as a major target for drug therapy.