PMID- 18620060
OWN - NLM
STAT- MEDLINE
DCOM- 20081029
LR  - 20211203
IS  - 1095-9327 (Electronic)
IS  - 1044-7431 (Linking)
VI  - 39
IP  - 1
DP  - 2008 Sep
TI  - Mammalian target of rapamycin (mTOR) is involved in the neuronal differentiation 
      of neural progenitors induced by insulin.
PG  - 118-24
LID - 10.1016/j.mcn.2008.06.003 [doi]
AB  - 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.
FAU - Han, Jin
AU  - Han J
AD  - Key laboratory of Molecular Developmental Biology, Institute of Genetics and 
      Developmental Biology, Chinese Academy of Sciences, Beijing 100190, China.
FAU - Wang, Bin
AU  - Wang B
FAU - Xiao, Zhifeng
AU  - Xiao Z
FAU - Gao, Yuan
AU  - Gao Y
FAU - Zhao, Yanhong
AU  - Zhao Y
FAU - Zhang, Jing
AU  - Zhang J
FAU - Chen, Bing
AU  - Chen B
FAU - Wang, Xia
AU  - Wang X
FAU - Dai, Jianwu
AU  - Dai J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080617
PL  - United States
TA  - Mol Cell Neurosci
JT  - Molecular and cellular neurosciences
JID - 9100095
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Insulin)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Cell Differentiation/*drug effects/physiology
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - Immunosuppressive Agents/metabolism
MH  - Insulin/*pharmacology
MH  - Neurons/cytology/*physiology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Protein Kinases/genetics/*metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/physiology
MH  - Sirolimus/metabolism
MH  - *Stem Cells/drug effects/physiology
MH  - TOR Serine-Threonine Kinases
EDAT- 2008/07/16 09:00
MHDA- 2008/10/31 09:00
CRDT- 2008/07/16 09:00
PHST- 2008/04/30 00:00 [received]
PHST- 2008/06/02 00:00 [revised]
PHST- 2008/06/05 00:00 [accepted]
PHST- 2008/07/16 09:00 [pubmed]
PHST- 2008/10/31 09:00 [medline]
PHST- 2008/07/16 09:00 [entrez]
AID - S1044-7431(08)00156-5 [pii]
AID - 10.1016/j.mcn.2008.06.003 [doi]
PST - ppublish
SO  - Mol Cell Neurosci. 2008 Sep;39(1):118-24. doi: 10.1016/j.mcn.2008.06.003. Epub 
      2008 Jun 17.