| 郭钰丽 闫浩 张荣庆 李聪叶 张英梅 王海昌.线粒体乙醛脱氢酶2(ALDH2)通过AMPK/FOXO3a 通路
改善高糖导致的心肌细胞凋亡[J].,2014,14(11):2024-2028 |
| 线粒体乙醛脱氢酶2(ALDH2)通过AMPK/FOXO3a 通路
改善高糖导致的心肌细胞凋亡 |
| Mitochondrial aldehyde dehydrogenase 2 (ALDH2) rescues highglucose-induced cardiomyocyte apoptosis through AMPK/FOXO3a pathway |
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| DOI： |
| 中文关键词: 乙醛脱氢酶2 高糖 心肌细胞 腺苷酸活化蛋白激酶 FOXO3a |
| 英文关键词: ALDH2 high glucose Myocardial cell AMPK FOXO3a |
| 基金项目:国家自然科学基金面上项目（81370195） |
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| 中文摘要: |
| 目的：观察乙醛脱氢酶2(ALDH2)对高糖诱导的H9C2 心肌细胞存活及凋亡的影响，并探讨腺苷酸活化蛋白激酶(AMPK)
/FOXO3a 信号通路在高糖导致的心肌细胞凋亡中的调控作用。方法：以30 mmol/L 葡萄糖诱导培养H9C2 心肌细胞48 h，经
ALDH2 激动剂Alda-1 及AMPK 抑制剂Compound C干预后，用MTT 法检测细胞的存活情况，TUNEL 试剂盒检测细胞凋亡情
况，Western blot检测ALDH2、磷酸化AMPK和FOXO3a 蛋白的表达水平。结果：与对照组相比，高浓度葡萄糖培养H9C2 心肌细
胞后，细胞的存活率显著降低、凋亡指数明显升高，磷酸化AMPK的表达水平明显上调，ALDH2 和磷酸化FOXO3a 的蛋白表达
显著降低(P<0.05)。ALDH2 的激动剂Alda-1 处理可显著提高高糖诱导的H9C2心肌细胞的存活率、降低其凋亡率，减少磷酸化
AMPK 的蛋白表达，增加ALDH2 的表达和FOXO3a 蛋白的磷酸化；而进一步采用AMPK 的抑制剂Compound C处理，可显著抑
制Alda-1 对高糖诱导的H9C2 心肌细胞的这些影响。结论：ALDH2 的激动剂Alda-1 对高糖诱导的心肌细胞凋亡具有保护作用，
可能与其激活AMPK，进而抑制心肌细胞FOXO3a 的活性有关。 |
| 英文摘要: |
| Objective: To observe the impact of ALDH2 on the cell viability and apoptosis of H9C2 cells, and explore the role of
adenosine monophosphate-activated protein kinase (AMPK)/FOXO3a pathways in high glocuse-induced apoptosis in the
cardiomyocytes.Methods: H9C2 cells were cultured in DMEMwith high doses (30 mM) of glucose for 48 h, in the absence or presence
of ALDH2 activator Alda-1 (20 滋M) and AMPK inhibitor CompoundC (10 mM). The cell viability was examined by MTT assay, the
apoptosis was measured by terminal deoxvnucleotidy1 transferase-mediated dUTP nick-end labeling (TUNEL) assay. Western blotting
was used to evaluate the expression of ALDH2, phosphorylated AMPK and FOXO3a.Results: Compared with the control group, the cell
viability, the expression of ALDH2 and p-FOXO3a were significantly decreased, cell apoptosis index and expression of p-AMPK were
markedly increased, in high concentration of glucose induced H9C2 cells (P<0.05). Alda-1 increased the cell viability, reduced the cell
apoptosis, and the expression of p-AMPK, upregulated the ALDH2 expression and phosphorylation of FOXO3a induced by high
concentration of glucose, these effect of Alda-1 was obliterated by Compound C.Conclusion:ALDH2 activator Alda-1 had a protective
effect on high glucose-induced cardiomyocyte injury, which may be mediated by the activation of AMPK and thus the suppression of
FOXO3a transcription factor activity. |
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