High glucose induces apoptosis and suppresses proliferation of adult rat neural stem cells following in vitro ischemia

BMC Neuroscience

Sheng Tan²  Zhenzhou Chen¹  Tianzhu Liu¹  Ruiqing Chen²  Wei Cheng²  Yang Guo²  Jian Chen² 

[1] Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China;Key Laboratory of Brain Function Repair and Regeneration of Guangdong, Department of Neurology, Zhujiang Hospital, Southern Medical University, Guangzhou, China

关键词: Mitogen-activated protein kinases (MAPKs);    Apoptosis;    Proliferation;    Hyperglycemia;    Neural stem cells;   

Others  :  1140439
DOI  :  10.1186/1471-2202-14-24

 received in 2012-10-04, accepted in 2013-02-27,  发布年份 2013

【 摘 要 】

Background

Post-stroke hyperglycemia appears to be associated with poor outcome from stroke, greater mortality, and reduced functional recovery. Focal cerebral ischemia data support that neural stem cells (NSCs) play an important role in post-ischemic repair. Here we sought to evaluate the negative effects of hyperglycemia on the cellular biology of NSCs following anoxia, and to test whether high glucose affects NSC recovery from ischemic injury.

Results

In this study, we used immortalized adult neural stem cells lines and we induced in vitro ischemia by 6 h oxygen and glucose deprivation (OGD) in an anaerobic incubator. Reperfusion was performed by returning cells to normoxic conditions and the cells were then incubated in experimental medium with various concentrations of glucose (17.5, 27.75, 41.75, and 83.75 mM) for 24 h. We found that high glucose (≥27.75 mM) exposure induced apoptosis of NSCs in a dose-dependent manner after exposure to OGD, using an Annexin V/PI apoptosis detection kit. The cell viability and proliferative activity of NSCs following OGD in vitro, evaluated with both a Cell Counting kit-8 (CCK-8) assay and a 5-ethynyl-2’-deoxyuridine (EdU) incorporation assay, were inhibited by high glucose exposure. Cell cycle analysis showed that high glucose exposure increased the percentage of cells in G0/G1-phase, and reduced the percentage of cells in S-phase. Furthermore, high glucose exposure was found to significantly induce the activation of c-Jun N-terminal protein kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) and suppress extracellular signal-regulated kinase 1/2 (ERK1/2) activity.

Conclusions

Our results demonstrate that high glucose induces apoptosis and inhibits proliferation of NSCs following OGD in vitro, which may be associated with the activation of JNK/p38 MAPK pathways and the delay of G1-S transition in the cells.

【 授权许可】

   
2013 Chen et al; licensee BioMed Central Ltd.

【 图 表 】

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