Exercise ameliorates the detrimental effect of chloroquine on skeletal muscles in mice via restoring autophagy flux. Acta Pharm Sin.
Dan Jiang, Kai Chen, Xuan Lu, Hong-Jian Gao, Zheng-Hong Qin, Fang Lin*.
Acta Pharmacol Sin. 2014 Jan; 35(1):135-42. ( IF=2.3)
Abstract:
Aim: To study the role of autophagy in muscle establishment during long term exercise.
Methods: The female mouse exercise model with wheel running scheduled was 6 m/min, 15 min/time, 3 times/d (on 8:00, 14:00, and 20:00), 5d/week for 2 months. Mice were also treated by autophagy activator trehalose (1% aqueous solution as a daily drinking water) or autophagy inhibitor chloroquine (intraperitoneal injection, 10mg/kg) before exercise training. The analysis of Western blot, TUNEL, H&E staining and transmission electron microscopic examination were employed to evaluate the autophagy level and muscle fibers structure.
Results: Exercise increased the antioxidant capacity, stimulated the formation of autophagosomes, increased LC3-II, Cathepsin L, Bcl-2 and lowered P62 and Bnip 3 levels. Meanwhile, the morphology of mitochondrial and the apoptosis significantly improved, and cytochrome c expression was higher in mitochondrial and lower in cytoplasm after the training. Trehalose increased autophagy level and protect the muscle fibers from apoptosis whereas chloroquine blocked autophagy flux and caused toxicity on skeletal muscles. Exercise could enhance the structure of skeletal muscle impaired by chloroquine.
Conclusion: Long-term regular exercise activated autophagy process which associated with muscle establishment, and exercise ameliorates the detrimental effect of chloroquine on skeletal muscles through restoring autophagy flux.
Keywords: autophagy; skeletal muscle; exercise; mitochondria; trehalose; chloroquine
