线粒体乙醛脱氢酶2通过提高细胞自噬改善高糖导致的心肌损伤
《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]
- 期数:
- 2015年第3期
- 页码:
- 249-254
- 栏目:
- 基础研究
- 出版日期:
- 2015-01-11
文章信息/Info
- Title:
- Mitochondrial aldehyde dehydrogenase 2 enhances cardiomyocytes viability exposed to high glucose by autophagy
- Author(s):
- LIU Min; ZHANG Le; MA Ying; MA Mei-juan; ZHANG Ying-mei; LI Yan
- (Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, China)
- Keywords:
- aldehyde dehydrogenase 2; autophagy; high glucose; myocardial cell; rat
- 分类号:
- R392.3
- DOI:
- -
- 文献标识码:
- A
- 摘要:
- 目的:明确乙醛脱氢酶2(ALDH2)对高糖状态下H9c2大鼠心肌细胞自噬表达水平的影响及其对细胞存活的作用。方法:以33 mmol/L葡萄糖培养大鼠H9c2心肌细胞72 h。经ALDH2激动剂Alda-1及自噬抑制剂3-甲基腺嘌呤(3-MA)干预后，用Western blot检测ALDH2、自噬基因相关蛋白5(ATG5)、微管相关蛋白质1轻链3(LC3)的表达水平。用免疫荧光法检测细胞内自噬体的数量，CCK-8法检测细胞的存活率，TUNEL法检测细胞凋亡。结果:与对照组相比，高糖导致心肌细胞自噬相关蛋白表达水平下降，减少自噬体的数量，降低细胞存活率，增加细胞凋亡；而ALDH2能提高高糖状态下自噬相关蛋白表达水平，增加自噬体的数量，增强细胞的存活率，减少细胞凋亡；应用自噬抑制剂3-MA处置后，可减弱ALDH2的上述作用。结论:ALDH2能够提高高糖状态下心肌细胞的自噬表达水平，提高细胞的存活率，减少细胞凋亡。
- Abstract:
- AIM:To investigate the role of ALDH2 in autophagy and cell survival in cardiomyocytes exposed to high glucose (HG). METHODS: H9c2 myocytes were cultured in DMEM with normal (5.5 mmol/L) or high doses (33 mmol/L) of glucose for 72 h in absence or presence of ALDH2 agonist Alda-1 (20 μmol/L) and autophagy inhibitor 3-methyladenine (3-MA) (10 mmol/L). The expression of ALDH2, autophagy gene-related protein 5 (ATG5), and microtubule-associated protein 1 light chain 3 (LC3) were analyzed by Western blot. The number of autophagosomes was measured by immunofluorescence, cell viability was detected by CCK-8 assay and the apoptotic index was examined by TUNEL. RESULTS: Compared with control group, HG induced decreased protein expression of ALDH2, ATG5 and LC3II, significantly reduced cell viability and increased the cell apoptosis index. Alda-1 upregulated the expression of ALDH2, ATG5 and LC3II and autophagosome cultured with high glucose, enhanced the cell viability and reduced the apoptosis index, which were reversed by 3-MA. CONCLUSION: ALDH2 increases cell viability and downregulates the apoptosis index in cardiomyocytes exposed to high glucose by autophagy.
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备注/Memo
- 备注/Memo:
- 收稿日期：2014-06-26.
基金项目：国家自然科学基金项目资助（81370195）
通讯作者：李妍，副教授，主要从事冠心病的基础和临床研究Email：liyanfmmu@hotmail.com
共同通讯作者：张英梅，副教授，主要从事糖尿病心肌病研究Email：Zhangym@fmmu.edu.cn
作者简介：刘敏，硕士生Email：lium418@sina.com
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