Neuronal expression and neuritogenic action of group X secreted phospholipase A2
Neuronal expression and neuritogenic action of group X secreted phospholipase A2
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DOI：
10.1074/jbc.m500985200
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发表时间：
2005-06-17
影响因子：
4.8
通讯作者：
Kudo, I
中科院分区：
文献类型：
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作者：
Masuda, S;Murakami, M;Kudo, I
尽管哺乳动物分泌型磷脂酶A（2）（sPLA（2））的酶表现出独特的组织和细胞分布，但每种酶的细胞类型特异性功能仍然很大程度上未知。在这项研究中，我们通过免疫组织化学发现，X组sPLA（2）（sPLA（2）-X）是唯一位于外周神经纤维，这一观察结果得到了其在神经元细胞系PC 12和原代背根神经节神经元中的转录本和蛋白检测的支持。在PC 12细胞中腺病毒表达的sPLA（2）-X促进了神经突起的生长，特别是当与次优浓度的神经生长因子结合时。在神经元分化的PC 12细胞中，sPLA（2）-X优先定位于高尔基体和生长锥，并且酶原向成熟酶的蛋白水解转化主要发生在分泌过程之后。sPLA（2）-X的神经突延伸能力依赖于其催化产物溶血磷脂酰胆碱的产生。此外，抗sPLA（2）-X抗体或针对sPLA（2）-X的小干扰RNA适度但显著地减弱了神经生长因子诱导的PC 12细胞的轴突延伸。这些观察结果表明，sPLA（2）-X对神经元分化的潜在贡献，并可能在某些条件下修复。
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.