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

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 A2s (sPLA2s) rescue CGNs from apoptosis after potassium deprivation. The neurotrophic effect required the enzymatic activity of sPLA2s, since catalytically inactive mutants of sPLA2s failed to protect CGNs from apoptosis. Consistently, the ability of sPLA2s to protect CGNs from apoptosis correlated with the extent of sPLA2-induced arachidonic acid release from live CGNs. The survival-promoting effect of sPLA2 was inhibited by depletion of extracellular Ca2+ or by the presence of L-type Ca2+ channel blocker nicardipine, suggesting that Ca2+ influx occurs upon sPLA2 treatment. Among the mammalian sPLA2s tested, only group X sPLA2, but not group IB nor IIA sPLA2s, displayed neurotrophic activity. These results suggest a novel, unexpected neurotrophin-like role of sPLA2 in the nervous system.