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 dependent 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 (approximately 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 contributing to excitotoxicity.