title: ALDH2 restores exhaustive exercise-induced mitochondrial dysfunction in skeletal muscle.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  ALDH2 may reverse skeletal muscle mitochondrial dysfunction due to exhaustive exercise by regulating mitochondria dynamic remodeling and enhancing the quality of mitochondria.
authors.affiliation: Key Laboratory of State General Administration of Sport, Shanghai Research Institute of Sports Science, Shanghai 200030, People's Republic of China.
authors.forename: Qiuping
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Key Laboratory of State General Administration of Sport, Shanghai Research Institute of Sports Science, Shanghai 200030, People's Republic of China.
authors.forename: Jianheng
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Key Laboratory of State General Administration of Sport, Shanghai Research Institute of Sports Science, Shanghai 200030, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Qiu
authors.affiliation: Key Laboratory of State General Administration of Sport, Shanghai Research Institute of Sports Science, Shanghai 200030, People's Republic of China.
authors.forename: Xiahong
authors.initials: X
authors.lastname: Wu
authors.affiliation: Key Laboratory of State General Administration of Sport, Shanghai Research Institute of Sports Science, Shanghai 200030, People's Republic of China.
authors.forename: Yangshuo
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Shanghai Key Laboratory of Hypertension, Department of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, People's Republic of China.
authors.forename: Weili
authors.initials: W
authors.lastname: Shen
authors.affiliation: Key Laboratory of State General Administration of Sport, Shanghai Research Institute of Sports Science, Shanghai 200030, People's Republic of China. Electronic address: sunmengwei@gmail.com.
authors.forename: Mengwei
authors.initials: M
authors.lastname: Sun
mesh_terms: D000071396:Aldehyde Dehydrogenase, Mitochondrial / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001343:Autophagy; D000071186:Beclin-1 / Q000378:metabolism; D015153:Blotting, Western; D015870:Gene Expression; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008931:Mitochondria, Muscle / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism*; D009133:Muscular Atrophy / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D010805:Physical Conditioning, Animal; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics; D013482:Superoxide Dismutase / Q000378:metabolism; D000070584:Tripartite Motif Proteins / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
chemical_list: D000071186:Beclin-1; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D009124:Muscle Proteins; D000070584:Tripartite Motif Proteins; D013482:Superoxide Dismutase; C515029:ALDH2 protein, mouse; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C486691:Fbxo32 protein, mouse; D044843:SKP Cullin F-Box Protein Ligases; C499084:Trim63 protein, mouse; D044767:Ubiquitin-Protein Ligases
keywords: ALDH2; Exhaustive exercise; Skeletal muscle