Mammalian target of rapamycin (mTOR) is involved in the neuronal differentiation of neural progenitors induced by insulin
Mammalian target of rapamycin (mTOR) is involved in the neuronal differentiation of neural progenitors induced by insulin
复制标题
DOI：
10.1016/j.mcn.2008.06.003
复制
发表时间：
2008-09-01
影响因子：
3.5
通讯作者：
Dai, Jianwu
中科院分区：
文献类型：
--
作者：
Han, Jin;Wang, Bin;Dai, Jianwu
神经前体细胞（NPC）的命运是由许多细胞外信号决定的。其中，胰岛素和胰岛素样生长因子（IGF）家族被发现促进NPC的神经元分化。Akt激活已被表明是胰岛素/IGF-I诱导的神经元分化的原因。然而，胰岛素/IGF-I-PI 3 K-Akt通路诱导NPC神经发生的机制尚不清楚。在这项研究中，我们已经证明了mTOR参与胰岛素诱导的神经元分化。胰岛素以剂量依赖性方式诱导NPC的神经发生。在胰岛素诱导的NPC分化过程中，磷酸化mTOR以PI 3 K-Akt依赖的方式上调。mTOR的特异性抑制剂雷帕霉素可以抑制胰岛素刺激的分化神经元的增加。此外，这不是神经元或NPC凋亡的结果。本研究为深入了解mTOR的功能和胰岛素调控鼻咽癌分化的机制提供了新的思路。(C)2008年爱思唯尔公司All rights reserved.
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 insuIin/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. (C) 2008 Elsevier Inc. All rights reserved.