Exercise ameliorates the detrimental effect of chloroquine on skeletal muscles in mice via restoring autophagy flux

• Published in: Acta pharmacologica Sinica Vol. 35; no. 1; pp. 135 - 142
• Main Authors: Jiang, Dan, Chen, Kai, Lu, Xuan, Gao, Hong-jian, Qin, Zheng-hong, Lin, Fang
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.01.2014
• Subjects: Animals; Antioxidants; Autophagy - drug effects; Autophagy - physiology; Chloroquine - toxicity; Female; ICR小鼠; Mice; Mice, Inbred ICR; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Original; Physical Conditioning, Animal - methods; Physical Conditioning, Animal - physiology; Quadriceps Muscle - drug effects; Quadriceps Muscle - metabolism; Quadriceps Muscle - pathology; Western印迹; 氯喹; 细胞质; 自噬作用; 运动训练; 通量; 骨骼肌
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/aps.2013.144

Aim： 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. Conclusion： 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.