Neuronal Expression and Neuritogenic Action of Group X Secreted Phospholipase A2

Abstract

Although individual mammalian secreted phospholipase A 2 (sPLA 2 ) enzymes exhibit unique tissue and cellular distributions, the cell type-specific functions of each enzyme remain largely unknown. In this study, we found by immunohistochemistry that group X sPLA 2 (sPLA 2 -X) is uniquely located in the peripheral neuronal fibers, an observation that was supported by detection of its transcript and protein in the neuronal cell line PC12 and in primary dorsal root ganglia neurons. Adenoviral expression of sPLA 2 -X in PC12 cells facilitated neurite outgrowth, particularly when combined with a suboptimal concentration of nerve growth factor. In neuronally differentiated PC12 cells, sPLA 2 -X was preferentially localized in the Golgi apparatus and growth cones, and proteolytic conversion of the proenzyme to mature enzyme mainly occurred after the secretion process. The neurite-extending ability of sPLA 2 -X depended on the production of its catalytic product, lysophosphatidylcholine. Moreover, nerve growth factor-induced neurite extension of PC12 cells was modestly but significantly attenuated by an anti-sPLA 2 -X antibody or by a small interfering RNA for sPLA 2 -X. These observations suggest the potential contribution of sPLA 2 -X to neuronal differentiation, and possibly repair, under certain conditions.

Phospholipase A2 and Signaling Pathways in Pheochromocytoma PC12 Cells

“…Such a "neuritogenic" property has been already reported for sPLA2s of groups IA and IB from cobra venom (Makarova et al, 2006;Osipov et al, 2010), IIA from viper venom (Makarova et al, 2006), III from bee venom (Nakashima et al, 2003) and from human neuronal cells (Masuda et al, 2008), V from mouse (Nakashima et al, 2003), X from mouse (Nakashima et al, 2003) and human (Ikeno et al, 2005;Masuda et al, 2005), as well as XIII from bacteria and fungi (Nakashima et al, 2003). According to the early report (Hanada et al, 1996), fungal PLA2 p15 promotes only NGF-induced neuritogenesis but itself alone fails to induce neurite outgrowth in PC12; however, under some conditions p15 can displays neuritogenic properties (Wakatsuki et al, 1999).…”

A new era of secreted phospholipase A2

“…sPLA 2 -V is an active mature enzyme ( 13 ). This processing occurs either before secretion intracellularly by furin-like convertase or after secretion extracellularly ( 108,109 ). Among the sPLA 2 s, sPLA 2 -X has the highest affi nity for PC and thus exhibits the most potent ability to hydrolyze plasma membrane phospholipids in intact cells ( 110,111 ).…”

Integration of cytokine biology and lipid metabolism in stroke

“…There have been few reports on the use of siRNA in animal models (193) and the development of appropriate vector systems is a prerequisite (194) before siRNA can be regarded as a suitable experimental tool for in vivo studies (195). Use of siRNA in cell culture has been achieved with striking potency at a relatively low concentration (190,196,199).…”