A novel neurotrophic role of secretory phospholipases A₂ for cerebellar granule neurons

Abstract

Cultured cerebellar granule neurons (CGNs) require membrane depolarization or neurotrophic factors for their survival in vitro and undergo apoptosis when deprived of these survival-promoting stimuli. Here, we show that secretory phospholipases A(2)s (sPLA(2)s) rescue CGNs from apoptosis after potassium deprivation. The neurotrophic effect required the enzymatic activity of sPLA(2)s, since catalytically inactive mutants of sPLA(2)s failed to protect CGNs from apoptosis. Consistently, the ability of sPLA(2)s to protect CGNs from apoptosis correlated with the extent of sPLA(2)-induced arachidonic acid release from live CGNs. The survival-promoting effect of sPLA(2) was inhibited by depletion of extracellular Ca(2+) or by the presence of L-type Ca(2+) channel blocker nicardipine, suggesting that Ca(2+) influx occurs upon sPLA(2) treatment. Among the mammalian sPLA(2)s tested, only group X sPLA(2), but not group IB nor IIA sPLA(2)s, displayed neurotrophic activity. These results suggest a novel, unexpected neurotrophin-like role of sPLA(2) in the nervous system.