PMID- 19909792
OWN - NLM
STAT- MEDLINE
DCOM- 20100308
LR  - 20220408
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 165
IP  - 3
DP  - 2010 Feb 3
TI  - Hypoxia stimulates proliferation of rat neural stem cells with influence on the 
      expression of cyclin D1 and c-Jun N-terminal protein kinase signaling pathway in 
      vitro.
PG  - 705-14
LID - 10.1016/j.neuroscience.2009.11.007 [doi]
AB  - Ischemia/hypoxia is known to induce the neural stem cells proliferation and 
      neural differentiation in rodent and human brain; however its mechanisms remain 
      largely unknown. In this study we investigated the effect of hypoxia on neural 
      stem cells (NSCs) proliferation with the expression of cyclin D1 and the 
      phosphorylation of mitogen-activated protein kinases (MAPK) signaling molecules. 
      NSCs were cultured from cortex of fetal Sprague-Dawley rats on embryonic day 5.5. 
      The hypoxia was made using a microaerophilic incubation system. The NSCs 
      proliferation was evaluated by 
      3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, 
      diameter measurement of neurospheres, bromodeoxyuridine (BrdU) incorporation 
      assay and cell cycle analysis. The cell death of NSCs was evaluated by terminal 
      dUTP nick-end labeling (TUNEL) assay. The expression of cyclin D1, phosphorylated 
      extracellular signal regulated kinase (ERK), c-Jun N-terminal protein kinase 
      (JNK) and p38 were analyzed by immunoblotting assay. The results showed that 
      hypoxia increased NSCs proliferation in cell amount, diameter of neurospheres, 
      BrdU incorporation and cell division, and the highest proliferation of the NSCs 
      was observed with 12 h hypoxic treatment; hypoxia did not decrease cell death of 
      NSCs; after hypoxic treatment, the expression of cyclin D1 increased, meanwhile 
      P-JNK2 level increased, P-p38 decreased, and no significant change in P-ERK2 
      level compared to normoxic cultures. JNK inhibitor SP600125 attenuated the 
      increase of cyclin D1 induced by hypoxia. These findings propose that hypoxia 
      increases cyclin D1 expression through activation of JNK in NSCs of rat in vitro, 
      suggesting a novel possible mechanism for hypoxia-induced proliferation of NSCs.
CI  - Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Chen, X
AU  - Chen X
AD  - Institute of Neurobiology, Environment and Genes Related to Diseases Key 
      Laboratory of Education Ministry, The State Key Subject for Physiology, Xi'an 
      Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, PR China.
FAU - Tian, Y
AU  - Tian Y
FAU - Yao, L
AU  - Yao L
FAU - Zhang, J
AU  - Zhang J
FAU - Liu, Y
AU  - Liu Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091110
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Ccnd1 protein, rat)
RN  - 136601-57-5 (Cyclin D1)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Animals
MH  - Apoptosis/physiology
MH  - Cell Cycle/physiology
MH  - Cell Hypoxia/physiology
MH  - *Cell Proliferation
MH  - Cells, Cultured
MH  - Cyclin D1/*metabolism
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism
MH  - MAP Kinase Signaling System/physiology
MH  - Neurons/enzymology/*physiology
MH  - Oxygen/*metabolism
MH  - Phosphorylation
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Stem Cells/enzymology/*physiology
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
EDAT- 2009/11/17 06:00
MHDA- 2010/03/10 06:00
CRDT- 2009/11/14 06:00
PHST- 2009/05/11 00:00 [received]
PHST- 2009/10/26 00:00 [revised]
PHST- 2009/11/04 00:00 [accepted]
PHST- 2009/11/14 06:00 [entrez]
PHST- 2009/11/17 06:00 [pubmed]
PHST- 2010/03/10 06:00 [medline]
AID - S0306-4522(09)01824-7 [pii]
AID - 10.1016/j.neuroscience.2009.11.007 [doi]
PST - ppublish
SO  - Neuroscience. 2010 Feb 3;165(3):705-14. doi: 10.1016/j.neuroscience.2009.11.007. 
      Epub 2009 Nov 10.