Roles of phospholipases A(2) in brain cell and tissue injury associated with ischemia and excitotoxicity

Phospholipase A(2) (PLA(2)) activity is an important contributor to destructive cellular processes in the central nervous system. Two cytosolic forms of calcium independent PLA(2) have been characterized in the gerbil brain and the neuronal cultures from rat brain. PLA(2) enzymatic activity in cell free extracts from cortical neuronal cultures is upregulated after cells are exposed to glutamate. Brief exposure to a calcium ionophore or phorbol 12-myristate 13-acetate (PMA) stably enhanced PLA(2) activity. Stable activation of the two cytosolic forms of PLA(2) occur prior to evidence of cell death and this activation is reversible. The larger molecular mass form was characterized as cPLA(2). The smaller form (similar to 14 kDa) was distinct from Group I and II PLA(2). Exposure to glutamate shifted the calcium activation curve of the smaller form to the left suggesting a novel mechanism of regulation of PLA(2). Glutamate-induced stable enhancement of PLA(2) activity, by processes involving calcium and protein kinase C activation, is a potential molecular switch likely mediating changes in synaptic function and contribution to excitotoxicity.