Han Jin, Wang Bin, Xiao Zhifeng, Gao Yuan, Zhao Yanhong, Zhang Jing, Chen Bing, Wang Xia, Dai Jianwu
Key laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100190, China.
Mol Cell Neurosci. 2008 Sep;39(1):118-24. doi: 10.1016/j.mcn.2008.06.003. Epub 2008 Jun 17.
The fate of neural progenitor cells (NPCs) is determined by many extracellular cues. Among them, insulin and insulin-like growth factor (IGF) family are found to promote the neuronal differentiation of NPCs. Akt activation has been indicated to be responsible for the insulin/IGF-I induced neuronal differentiation. However, the mechanism by which insulin/IGF-I-PI3K-Akt pathway induces neurogenesis of NPCs is not clear. In this study, we have demonstrated that mTOR is involved in the insulin-induced neuronal differentiation. Insulin induces neurogenesis of NPCs in a dose-dependent manner. Phosphorylated mTOR has been up-regulated in a PI3K-Akt dependent manner during NPC differentiation induced by insulin. The specific inhibitor of mTOR, rapamycin, can abrogate the increase of differentiated neurons stimulated by insulin. In addition, this is not the result from the apoptosis of neurons or NPCs. This research has extended the understanding of functions of mTOR and the mechanism of NPC differentiation regulated by insulin.
神经祖细胞(NPCs)的命运由许多细胞外信号决定。其中,胰岛素和胰岛素样生长因子(IGF)家族被发现可促进NPCs的神经元分化。已有研究表明Akt激活介导胰岛素/IGF-I诱导的神经元分化。然而,胰岛素/IGF-I-PI3K-Akt信号通路诱导NPCs神经发生的机制尚不清楚。在本研究中,我们证实mTOR参与胰岛素诱导的神经元分化。胰岛素以剂量依赖的方式诱导NPCs的神经发生。在胰岛素诱导的NPCs分化过程中,磷酸化的mTOR以PI3K-Akt依赖的方式上调。mTOR的特异性抑制剂雷帕霉素可消除胰岛素刺激引起的分化神经元增加。此外,这并非神经元或NPCs凋亡的结果。本研究拓展了对mTOR功能以及胰岛素调节NPCs分化机制的认识。