Lysophosphatidylethanolamine in Grifola frondosa as a neurotrophic activator via activation of MAPK
Lysophosphatidylethanolamine in Grifola frondosa as a neurotrophic activator via activation of MAPK
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DOI：
10.1194/jlr.m600045-jlr200
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发表时间：
2006-07-01
影响因子：
6.5
通讯作者：
Furukawa, Shoei
中科院分区：
文献类型：
--
作者：
Nishina, Atsuyoshi;Kimura, Hirokazu;Furukawa, Shoei
我们发现，灰树花提取物诱导有丝分裂原活化蛋白激酶（MAPK）在培养的PC 12细胞，一个线的大鼠嗜铬细胞瘤细胞。通过几个色谱步骤（包括高效液相色谱法）分离活性物质，并通过各种结构分析鉴别为溶血磷脂酰乙醇胺（LPE）。从G.灰树花提取物（GLPE）能诱导体外培养的PC 12细胞MAPK活化，并能抑制血清剥夺诱导的细胞凝聚和DNA梯状条带的产生，提示GLPE具有抗凋亡作用。此外，GLPE引起的形态学变化和上调的神经丝M表达的PC 12细胞，表明GLPE可以诱导这些细胞的神经元分化。表皮生长因子受体（EGFR）拮抗剂AG 1478和MAPK激酶（MEK 1/2）抑制剂U 0126可抑制GLPE对MAPK的激活作用，而TrkA抑制剂K252 a和百日咳毒素则不能抑制GLPE对MAPK的激活作用。这些结果表明，GLPE诱导PC 12细胞的MAPK级联[EGFR-MEK 12-细胞外信号调节蛋白激酶（ERK 12）]，其激活诱导神经元分化并抑制血清剥夺诱导的凋亡。本研究首次阐明了MAPK信号级联在LPE作用中的参与。
We found that Grifola frondosa extracts induced the activation of mitogen-activated protein kinase ( MAPK) in cultured PC12 cells, a line of rat pheochromocytoma cells. The active substance was isolated by a few chromatographic steps, including high-performance liquid chromatography, and was identified to be lysophosphatidylethanolamine (LPE) from various structural analyses. LPE from G. frondosa ( GLPE) was confirmed to induce the activation of MAPK of cultured PC12 cells and was found to suppress cell condensation and DNA ladder generation evoked by serum deprivation, suggesting that the GLPE had antiapoptotic effects. Moreover, GLPE caused morphological changes in and upregulation of neurofilament M expression of PC12 cells, demonstrating that the GLPE could induce neuronal differentiation of these cells. The activation of MAPK by GLPE was suppressed by AG1478, an antagonist of epidermal growth factor receptor ( EGFR), and by U0126, an inhibitor of MAPK kinase (MEK1/2), but not by K252a, an inhibitor of TrkA, or by pertussis toxin. These results demonstrate that GLPE induced the MAPK cascade [EGFR-MEK1/2-extracellular signal-regulated protein kinases (ERK1/2)] of PC12 cells, the activation of which induced neuronal differentiation and suppressed serum deprivation-induced apoptosis. This study has clarified for the first time the involvement of the MAPK signal cascade in LPE actions.