Lysophosphatidylcholine enhances NGF-induced MAPK and Akt signals through the extracellular domain of TrkA in PC12 cells.
Lysophosphatidylcholine enhances NGF-induced MAPK and Akt signals through the extracellular domain of TrkA in PC12 cells.
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DOI：
10.1016/j.fob.2013.05.003
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发表时间：
2013
期刊：
影响因子：
2.6
通讯作者：
Arioka M
中科院分区：
文献类型：
--
作者：
Wuhanqimuge;Itakura A;Matsuki Y;Tanaka M;Arioka M
溶血磷脂酰胆碱（LPC）是主要由磷脂酶A2（PLA 2）介导的磷脂酰胆碱（PC）水解产生的主要溶血磷脂之一。我们以前发现LPC在大鼠嗜铬细胞瘤PC 12细胞和小脑颗粒神经元中显示神经营养素样活性，但分子机制尚不清楚。我们在这里报告，LPC特异性增强神经生长因子（NGF）诱导的信号在PC 12细胞。当用NGF处理PC 12细胞时，MAPK被磷酸化，但当LPC一起加入时，这种磷酸化显著升高。与此一致，LPC上调了NGF诱导的即刻早期基因c-fos和NGF-IA的表达。磷酸化的上游组件，MEK和神经生长因子受体TrkA，也促进LPC，这是在增加Akt的磷酸化。与此相反，LPC没有增强表皮生长因子（EGF），碱性成纤维细胞生长因子，或胰岛素样生长因子-1诱导的信号。使用TrkA/EGF受体嵌合体的研究表明，TrkA的胞外结构域，而不是跨膜或胞内结构域，是LPC的作用的原因。外源性添加的分泌型PLA 2（sPLA 2）增强了NGF诱导的MAPK磷酸化水平与LPC相当，表明LPC原位产生的sPLA 2介导的水解膜PC刺激NGF-TrkA信号。综上所述，这些结果表明LPC对NGF-TrkA信号通路的特定作用和功能。LPC增强PC 12细胞中NGF诱导的MAPK和Akt磷酸化。LPC增强NGF诱导的MEK和TrkA磷酸化。LPC不影响EGF、FGF和IGF-1的信号。LPC的作用需要TrkA的胞外结构域。sPLA 2还增强NGF诱导的MAPK磷酸化。
Lysophosphatidylcholine (LPC) is one of the major lysophospholipids mainly generated by phospholipase A2 (PLA2)-mediated hydrolysis of phosphatidylcholine (PC). We previously found that LPC displays neurotrophin-like activity in the rat pheochromocytoma PC12 cells and in cerebellar granule neurons, but the molecular mechanism remains unclear. We report here that LPC specifically enhances nerve growth factor (NGF)-induced signals in PC12 cells. When PC12 cells were treated with NGF, MAPK was phosphorylated, but this phosphorylation was significantly elevated when LPC was added together. In accordance, NGF-induced expression of immediate early genes, c-fos and NGF-IA, was upregulated by LPC. Phosphorylation of the upstream components, MEK and NGF receptor TrkA, was also promoted by LPC, which was in line with increased phosphorylation of Akt. In contrast, LPC did not enhance epidermal growth factor (EGF)-, basic fibroblast growth factor-, or insulin-like growth factor-1-induced signals. Studies using TrkA/EGF receptor chimeras demonstrated that the extracellular domain, but not the transmembrane or intracellular domains, of TrkA is responsible for the effect of LPC. Exogenously-added secretory PLA2 (sPLA2) enhanced NGF-induced MAPK phosphorylation at a comparable level to LPC, suggesting that LPC generated in situ by sPLA2-mediated hydrolysis of membrane PC stimulated NGF-TrkA signal. Taken together, these results indicate a specific role and function of LPC on NGF-TrkA signaling pathway. LPC potentiates NGF-induced MAPK and Akt phosphorylation in PC12 cells. LPC enhances NGF-induced MEK and TrkA phosphorylation. LPC does not affect the signals of EGF, FGF, and IGF-1. The effect of LPC requires the extracellular domain of TrkA. sPLA2 also potentiates NGF-induced MAPK phosphorylation.