Human group III secreted phospholipase A₂ promotes neuronal outgrowth and survival

Human sPLA₂-III [group III secreted PLA₂ (phospholipase A₂)] is an atypical sPLA₂ isoenzyme that consists of a central group III sPLA₂ domain flanked by unique N- and C-terminal domains. In the present study, we found that sPLA₂-III is expressed in neuronal cells, such as peripheral neuronal fibres, spinal DRG (dorsal root ganglia) neurons and cerebellar Purkinje cells. Adenoviral expression of sPLA₂-III in PC12 cells (pheochromocytoma cells) or DRG explants facilitated neurite outgrowth, whereas expression of a catalytically inactive sPLA₂-III mutant or use of sPLA₂-III-directed siRNA (small interfering RNA) reduced NGF (nerve growth factor)-induced neuritogenesis. sPLA₂-III also suppressed neuronal death induced by NGF deprivation. Lipid MS revealed that sPLA₂-III overexpression increased the cellular level of lysophosphatidylcholine, a PLA₂ reaction product with neuritogenic and neurotropic activities, whereas siRNA knockdown reduced the level of lysophosphatidylcholine. These observations suggest the potential contribution of sPLA₂-III to neuronal differentiation and its function under certain conditions.