Roles of phospholipases A2 in brain cell and tissue injury associated with ischemia and excitotoxicity

Abstract

Phospholipase A₂ (PLA₂) activity is an important contributor to destructive cellular processes in the central nervous system. Two cytosolic forms of calcium independent PLA₂ have been characterized in the gerbil brain and the neuronal cultures from rat brain. PLA₂ 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 PLA₂ activity. Stable activation of the two cytosolic forms of PLA₂ occur prior to evidence of cell death and this activation is reversible. The larger molecular mass form was characterized as cPLA₂. The smaller form (∼ 14 kDa) was distinct from Group I and II PLA₂. Exposure to glutamate shifted the calcium activation curve of the smaller form to the left suggesting a novel mechanism of regulation of PLA₂. Glutamate-induced stable enhancement of PLA₂ 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.