Effect of hypoxia on 2-deoxyglucose uptake and cell cycle regulatory protein expression of mouse embryonic stem cells:: Involvement of Ca2+/PKC, MAPKs and HIF-1α

被引:28
作者
Lee, Sang Hun [1 ]
Heo, Jung Sun [1 ]
Han, Ho Jae [1 ]
机构
[1] Chonnam Natl Univ, Coll Vet Med, Dept Vet Physiol, Biotherapy Human Resources Ctr,BK21, Kwangju 500757, South Korea
关键词
embryonic stem (ES) cell; hypoxia; 2-DG uptake; cell cycle regulatory proteins; PKC; p44/42; MAPKs;
D O I
10.1159/000100646
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
This study investigated the signal molecules linking the alteration in 2-dexoyglucose (2-DG) uptake and DNA synthesis in mouse embryonic stem (ES) cells under hypoxia. Hypoxia increased the 2-DG uptake and GLUT-1 protein expression level while the undifferentiated state of ES cells and cell viability were not affected by the hypoxia (1-48h). Subsequently, [H-3] thymidine incorporation was significantly increased at 12 hours of hypoxic exposure. Hypoxia increased the Ca2+ uptake and PKC beta(1), epsilon, and zeta translocation from the cytosol to the membrane fraction. Moreover, hypoxia increased the level of p44/42 mitogen-activated protein kinases (MAPKs) phosphorylation and hypoxia inducible factor-1 alpha (HIF-1 alpha) in a time-dependent manner. On the other hand, inhibition of these pathways blocked the hypoxia-induced increase in the 2-DG uptake and GLUT-1 protein expression level. Under hypoxia, cell cycle regulatory protein expression [cyclin D1, cyclin E, cyclin-dependent kinase (CDK) 2, and CDK 4] were increased in a time-dependent manner, which were blocked by PD 98059. pRB protein was also increased in a time-dependent manner. In conclusion, under hypoxia, there might be a parallel relationship between the expression of GLUT1 and DNA synthesis, which is mediated by the Ca2+/ PKC, MAPK, and the HIF-1 alpha signal pathways in mouse ES cells. Copyright (c) 2007 S. Karger AG, Basel.
引用
收藏
页码:269 / 282
页数:14
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