Masuda Seiko, Yamamoto Kei, Hirabayashi Tetsuya, Ishikawa Yukio, Ishii Toshiharu, Kudo Ichiro, Murakami Makoto
Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan.
Biochem J. 2008 Jan 15;409(2):429-38. doi: 10.1042/BJ20070844.
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.
人分泌型磷脂酶A2-III [III组分泌型磷脂酶A2（磷脂酶A2）]是一种非典型的分泌型磷脂酶A2同工酶，由一个中央III组分泌型磷脂酶A2结构域以及两侧独特的N端和C端结构域组成。在本研究中，我们发现分泌型磷脂酶A2-III在神经元细胞中表达，如外周神经纤维、脊髓背根神经节（DRG）神经元和小脑浦肯野细胞。分泌型磷脂酶A2-III在PC12细胞（嗜铬细胞瘤细胞）或DRG外植体中的腺病毒表达促进了神经突生长，而催化失活的分泌型磷脂酶A2-III突变体的表达或使用针对分泌型磷脂酶A2-III的小干扰RNA（siRNA）则减少了神经生长因子（NGF）诱导的神经突发生。分泌型磷脂酶A2-III还抑制了由NGF剥夺诱导的神经元死亡。脂质质谱分析显示，分泌型磷脂酶A2-III的过表达增加了溶血磷脂酰胆碱的细胞水平，溶血磷脂酰胆碱是一种具有神经突发生和神经营养活性的磷脂酶A2反应产物，而siRNA敲低则降低了溶血磷脂酰胆碱的水平。这些观察结果表明分泌型磷脂酶A2-III在神经元分化及其在某些条件下的功能中具有潜在作用。
