Secretory phospholipases A2 induce neurite outgrowth in PC12 cells through lysophosphatidylcholine generation and activation of G2A receptor

We previously demonstrated that secretory phospholipase A(2) (sPLA(2)) and lysophosphatidylcholine (LPC) exhibit neurotrophin-like neuritogenic activity in the rat pheochromocytoma cell line PC12. In this study, we further analyzed the mechanism whereby sPLA2 displays neurite-inducing activity. Exogenously added mammalian group X sPLA(2) (sPLA(2)-X), but not group IB and IIA sPLA(2)s, induced neuritogenesis, which correlated with the ability of sPLA(2)-X to liberate LPC into the culture media. In accordance, blocking the effect of LPC by supplementation of bovine serum albumin or phospholipase B attenuated neuritogenesis by sPLA(2) or LPC. Overproduction or suppression of G2A, a G-protein-coupled receptor involved in LPC signaling, resulted in the enhancement or reduction of neuritogenesis induced by sPLA(2) treatment. These results indicate that the neuritogenic effect of sPLA(2) is mediated by generation of LPC and subsequent activation of G2A.