Human sPLA(2)-III [group III secreted PLA(2) (phospholipase A(2))] is an atypical sPLA(2) isoenzyme that consists of a central group III sPLA(2) domain flanked by unique N- and C-terminal domains. In the present study, we found that sPLA(2)-III is expressed in neuronal cells, such as peripheral neuronal fibres, spinal DRG (dorsal root ganglia) neurons and cerebellar Purkinje cells. Adenoviral expression of sPLA(2)-III in PC12 cells (pheochromocytoma cells) or DRG explants facilitated neurite outgrowth, whereas expression of a catalytically inactive sPLA(2)-III mutant or use of sPLA(2)-III-directed siRNA (small interfering RNA) reduced NGF (nerve growth factor)-induced neuritogenesis. sPLA(2)-III also suppressed neuronal death induced by NGF deprivation. Lipid MS revealed that sPLA(2)-III overexpression increased the cellular level of lysophosphatidylcholine, a PLA(2) reaction product with neuritogenic and neurotropic activities, whereas siRNA knockdown reduced the level of lysophosphatidylcholine. These observations suggest the potential contribution of sPLA(2)-III to neuronal differentiation and its function under certain conditions.
Human group III secreted phospholipase A(2) promotes neuronal outgrowth and survival. Publishing Authors By Initials
