Liu Jianhui, Zheng Xuxu, Yin Fei, Hu Yinhe, Guo Lixia, Deng Xiaohong, Chen Gang, Jiajia Jing, Zhang Heng
Research Center of Pharmaceutical Chemistry & Chemobiology, Chongqing Technology and Business University, Chongqing 400067, China.
Int J Dev Neurosci. 2006 Nov;24(7):419-24. doi: 10.1016/j.ijdevneu.2006.08.009. Epub 2006 Oct 11.
The emerging data show that the insulinotrophic hormone glucagon-like peptide-1(GLP-1) and its agonist extendin-4 have neurotrophic function to inducing neuronal differentiation of PC12 cells and prevent neurons damage challenged by oxidative stress. Here, with the model of high throughput screen for GLP-1 receptor agonists, we screen and identify that geniposide is a novel agonist for GLP-1 receptor. Furthermore, geniposide induces the neuronal differentiation of PC12 cells with resulting neurites outgrowth; we also observe an increase in expression of growth-associated protein-43. U0126, a selective MEK inhibitor, prevents neurites out growth and phosphorylation of mitogen-activated kinase proteins in PC12 cells induced by geniposide. All these results show that activation of GLP-1 receptor by geniposide to induce the neuronal differentiation of PC12 cells involves in MAPK signaling cascade.
新出现的数据表明，促胰岛素激素胰高血糖素样肽-1（GLP-1）及其激动剂艾塞那肽-4具有神经营养功能，可诱导PC12细胞的神经元分化，并预防氧化应激所引发的神经元损伤。在此，利用针对GLP-1受体激动剂的高通量筛选模型，我们筛选并鉴定出栀子苷是一种新型GLP-1受体激动剂。此外，栀子苷可诱导PC12细胞的神经元分化并导致神经突生长；我们还观察到生长相关蛋白-43的表达增加。U0126，一种选择性MEK抑制剂，可阻止栀子苷诱导的PC12细胞中的神经突生长和丝裂原活化激酶蛋白的磷酸化。所有这些结果表明，栀子苷激活GLP-1受体以诱导PC12细胞的神经元分化涉及丝裂原活化蛋白激酶信号级联反应。
