title: Exercise ameliorates the detrimental effect of chloroquine on skeletal muscles in mice via restoring autophagy flux.
abstract: OBJECTIVE
  To study the roles of autophagy in muscle establishment during long-term exercise in mice.
  
  
  METHODS
  Female ICR mice were submitted to exercise training with a wheel running regimen: 6 m/min, 15 min/time, 3 times/d (on 8:00, 14:00, and 20:00), 5 d/week for 2 months. The mice were treated with the autophagy activator trehalose (1% aqueous solution as a daily drinking water) or the autophagy inhibitor chloroquine (10 mg/kg, ip, 5 times a week) before the training. Western blotting analysis, TUNEL staining, H&E staining and transmission electron microscope were used to evaluate the activity of autophagy and the structure of the muscle fibers.
  
  
  RESULTS
  The exercise training significantly stimulated the formation of autophagosomes, increased the LC3-II, cathepsin L and Bcl-2 levels, lowered the P62 level and increased the antioxidant capacity in the muscles. Meanwhile, the exercise training significantly improved the morphology of mitochondria, reduced the release of cytochrome c from mitochondria to cytoplasm, and slightly decreased the apoptosis rate in the muscles. Administration of trehalose increased the level of autophagy and protected the muscle fibers from apoptosis. Administration of chloroquine blocked autophagy flux and exerted detrimental effects on the muscles, which were ameliorated by the exercise training.
  
  
  CONCLUSIONS
  Long-term regular exercise activates autophagy process associated with muscle establishment, and ameliorates the detrimental effects of chloroquine on skeletal muscles via restoring autophagy flux.
authors: Department of Pharmacology, Laboratory of Aging and Nervous Diseases (SZS0703), Soochow University School of Pharmaceutical Science, Suzhou 215123, China.
authors: Dan
authors: D
authors: Jiang
authors: Department of Cancer, the First Affiliated Hospital of Soochow University, Suzhou 215006, China.
authors: Kai
authors: K
authors: Chen
authors: Department of Pharmacology, Laboratory of Aging and Nervous Diseases (SZS0703), Soochow University School of Pharmaceutical Science, Suzhou 215123, China.
authors: Xuan
authors: X
authors: Lu
authors: Electron Microscopy Core Laboratory, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors: Hong-jian
authors: HJ
authors: Gao
authors: Department of Pharmacology, Laboratory of Aging and Nervous Diseases (SZS0703), Soochow University School of Pharmaceutical Science, Suzhou 215123, China.
authors: Zheng-hong
authors: ZH
authors: Qin
authors: Department of Pharmacology, Laboratory of Aging and Nervous Diseases (SZS0703), Soochow University School of Pharmaceutical Science, Suzhou 215123, China.
authors: Fang
authors: F
authors: Lin
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D002738:Chloroquine / Q000633:toxicity*; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D010805:Physical Conditioning, Animal / Q000379:methods / Q000502:physiology*; D052097:Quadriceps Muscle / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D002738:Chloroquine