Phospholipase A2 (PLA2) activity in gerbil brain: characterization of cytosolic and membrane-associated forms and effects of ischemia and reperfusion on enzymatic activity.

Phospholipases A2 comprise a family of enzymes that hydrolyze the acyl bond at the sn-2 position of phospholipids to generate free fatty acids and lysophospholipids. In the central nervous system products of PLA2 regulate neurotransmission. In addition, the lysophospholipids, free fatty acids, eicosanoids, platelet activating factor and reactive oxygen species, generated by enhanced PLA2 activity and arachidonic acid metabolism, may be responsible for many destructive cellular processes in neuronal tissue. There are interactions between glutamate and PLA2 and its products which suggest that PLA2 activity plays an important role in excitotoxic neuronal cell injury associated with ischemia. Our laboratory has demonstrated that multiple forms of Ca(2+)-dependent PLA2 are present in the gerbil brain. These forms differ from previously described forms and from each other. After ischemia and reperfusion, cytosolic, mitochondrial/synaptosomal and microsomal PLA2 enzymatic activities are enhanced. These stable modifications of enzymatic activity cannot be explained by a direct effect of Ca2+ alone and our data suggest that regulatory influences other than Ca2+ may play an important role in PLA2 activation and mediation of cellular injury after an ischemic insult.