ROLES OF PHOSPHOLIPASES A(2) IN BRAIN-CELL AND TISSUE-INJURY ASSOCIATED WITH ISCHEMIA AND EXCITOTOXICITY (VOL 14, PG 15, 1996)

Phospholipase A(2) (PLA(2)) activity is an important contributor to de structive cellular processes in the central nervous system. Two cytoso lic forms of calcium dependent PLA(2) have been characterized in the g erbil brain and the neuronal cultures from rat brain. PLA(2) enzymatic activity in cell free extracts from cortical neuronal cultures is upr egulated after cells are exposed to glutamate. Brief exposure to a cal cium ionophore or phorbol 12-myristate 13-acetate (PMA) stably enhance d PLA(2) activity. Stable activation of the two cytosolic forms of PLA (2) occur prior to evidence of cell death and this activation is rever sible. The larger molecular mass form was characterized as cPLA(2). Th e smaller form (similar to 14 kDa) was distinct from Group I and II PL A(2). Exposure to glutamate shifted the calcium activation curve of th e 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 pot ential molecular switch likely mediating changes in synaptic function and contributing to excitotoxicity.