线粒体乙醛脱氢酶2在有氧运动抑制衰老骨骼肌细胞凋亡中的作用及机制

项目名称： 线粒体乙醛脱氢酶2在有氧运动抑制衰老骨骼肌细胞凋亡中的作用及机制

项目编号： No.31500961

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生理学与整合生物学

项目作者： 李方晖

作者单位： 肇庆学院

项目金额： 20万元

中文摘要： 体育运动可通过抑制肌细胞凋亡来防治肌肉减少症，但具体机制不清。我们前期实验从蛋白质组学角度揭示了有氧运动改善肌肉减少症的整体机制，筛选出生物标示物线粒体乙醛脱氢酶2(ALDH2)。已知ALDH2基因缺失导致的4-羟基壬烯醛(4-HNE)积累会引起骨骼肌氧化损伤和线粒体功能失调。研究证实老龄骨骼肌4-HNE增加与肌细胞凋亡有关。据此推测“衰老肌细胞凋亡与ALDH2活性下调有关，有氧运动经ALDH2抑制肌细胞凋亡来防治肌肉减少症”。为了证实该假说，本课题进一步观察不同鼠龄大鼠骨骼肌ALDH2活性与肌细胞凋亡关联，给予ALDH2抑制剂，证实ALDH2介导有氧运动的保护作用。体外培养大鼠骨骼肌细胞，探讨ALDH2对自噬、线粒体损伤和凋亡的影响，证明ALDH2发挥作用依赖的信号级联。本课题首次在器官、细胞及分子水平上探讨ALDH2介导有氧运动抑制肌细胞凋亡及其机制，为肌肉减少症的防治提供理论基础。

中文关键词： 肌少症；有氧运动；细胞凋亡；乙醛脱氢酶2；自噬

英文摘要： Physical exercise is currently considered the primary countermeasure to sarcopenia through attenuating age-related increase in myocyte apoptosis. However, the underlying cellular and molecular mechanisms are not well understood. We used an unbiased proteomic approach reveal the overall mechanism of the aerobic exercise improved sarcopenia. As a biomarkers, mitochondrial aldehyde dehydrogenase 2 (ALDH2) was identified further. Recent evidence has insinuated that loss of ALDH2 enzyme in the knockout mice cause accumulation of mitochondrial 4-HNE, which may contribute to skeletal muscle oxidative damage and mitochondrial dysfunction. The previous study confirmed that 4-HNE is closely related to age-related increase in myocyte apoptosis. It may thus be speculated that ALDH2 deficiency augments skeletal muscle 4-HNE levels, exacerbates muscle cell mitochondrial damage and apoptosis, the aerobic exercise may be inhibit myocyte apoptosis through upregulating the activity and expression of ALDH2. The present study is designed to evaluate the impact of ALDH2 activity on age-related increase in myocyte apoptosis and ALDH2 inhibitor was administrated，confirming that ALDH2 plays a pivotal positive role in mediating the aerobic exercise against myocyte apoptosis. Culture L6 muscle cells in vitro, to investigate the effect of ALDH2 on autophagy, apoptosis, mitochondrial damage, reveal which ALDH2 act via pathways. This project is the first study evaluating ALDH2-mediated protection of myocyte apoptosis by the aerobic exercise on both a cellular and a molecular level.

英文关键词： Sarcopenia;aerobic exercise;apoptosis;ALDH2;autophagy