Zhang Qiuping, Zheng Jianheng, Qiu Jun, Wu Xiahong, Xu Yangshuo, Shen Weili, Sun Mengwei
Key Laboratory of State General Administration of Sport, Shanghai Research Institute of Sports Science, Shanghai 200030, People's Republic of China.
Shanghai Key Laboratory of Hypertension, Department of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, People's Republic of China.
Biochem Biophys Res Commun. 2017 Apr 15;485(4):753-760. doi: 10.1016/j.bbrc.2017.02.124. Epub 2017 Feb 27.
Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is highly expressed in heart and skeletal muscles, and is the major enzyme that metabolizes acetaldehyde and toxic aldehydes. The cardioprotective effects of ALDH2 during cardiac ischemia/reperfusion injury have been recognized. However, less is known about the function of ALDH2 in skeletal muscle. This study was designed to evaluate the effect of ALDH2 on exhaustive exercise-induced skeletal muscle injury.
We created transgenic mice expressing ALDH2 in skeletal muscles. Male wild-type C57/BL6 (WT) and ALDH2 transgenic mice (ALDH2-Tg), 8-weeks old, were challenged with exhaustive exercise for 1 week to induce skeletal muscle injury. Animals were sacrificed 24 h post-exercise and muscle tissue was excised.
ALDH2-Tg mice displayed significantly increased treadmill exercise capacity compared to WT mice. Exhaustive exercise caused an increase in mRNA levels of the muscle atrophy markers, Atrogin-1 and MuRF1, and reduced mitochondrial biogenesis and fusion in WT skeletal muscles; these effects were attenuated in ALDH2-Tg mice. Exhaustive exercise also enhanced mitochondrial autophagy pathway activity, including increased conversion of LC3-I to LC3-II and greater expression of Beclin1 and Bnip3; the effects of which were mitigated by ALDH2 overexpression. In addition, ALDH2-Tg reversed the increase of an oxidative stress biomarker (4-hydroxynonenal) and decreased levels of mitochondrial antioxidant proteins, including manganese superoxide dismutase and NAD(P)H:quinone oxidoreductase 1, in skeletal muscle induced by exhaustive exercise.
ALDH2 may reverse skeletal muscle mitochondrial dysfunction due to exhaustive exercise by regulating mitochondria dynamic remodeling and enhancing the quality of mitochondria.
线粒体乙醛脱氢酶2（ALDH2）在心脏和骨骼肌中高表达，是代谢乙醛和有毒醛类的主要酶。ALDH2在心脏缺血/再灌注损伤期间的心脏保护作用已得到认可。然而，关于ALDH2在骨骼肌中的功能知之甚少。本研究旨在评估ALDH2对力竭运动诱导的骨骼肌损伤的影响。
我们构建了在骨骼肌中表达ALDH2的转基因小鼠。8周龄的雄性野生型C57/BL6（WT）和ALDH2转基因小鼠（ALDH2-Tg）接受1周的力竭运动以诱导骨骼肌损伤。运动后24小时处死动物并切除肌肉组织。
与WT小鼠相比，ALDH2-Tg小鼠的跑步机运动能力显著提高。力竭运动导致WT骨骼肌中肌肉萎缩标志物Atrogin-1和MuRF1的mRNA水平升高，并减少线粒体生物发生和融合；这些效应在ALDH2-Tg小鼠中减弱。力竭运动还增强了线粒体自噬途径活性，包括LC3-I向LC3-II的转化增加以及Beclin1和Bnip3的表达增加；ALDH2过表达减轻了这些效应。此外，ALDH2-Tg逆转了力竭运动诱导的骨骼肌中氧化应激生物标志物（4-羟基壬烯醛）的增加以及线粒体抗氧化蛋白水平的降低，包括锰超氧化物歧化酶和NAD(P)H：醌氧化还原酶1。
ALDH2可能通过调节线粒体动态重塑和提高线粒体质量来逆转力竭运动引起的骨骼肌线粒体功能障碍。
