The Regulatory Mechanism of Autophagy Pathway in Hypoxia Exposure-Induced Skeletal Muscle Atrophy

FU Pengyu¹^,2, JIA Jie², ZHU Rongxin³, YU Jiabei⁴, ZOU Beiyang², GONG Lijing²^,5*

(¹Department of Physical Education, Northwestern Polytechnical University, Xi’an 710072, China; ²China Institute of Sport and Health Science, Beijing Sport University, Beijing 100084, China; ³Shanghai Research Institute of Sports Science (Shanghai Anti-Doping Center), Shanghai 200030, China; ⁴Beijing Research Institute of Sports Science, Beijing 100075, China; ⁵Key Laboratory of Physical Fitness and Exercise, Ministry of Education, Beijing Sport University, Beijing 100084, China)

Abstract:

This study intends to observe the phenomenon of hypoxia exposure-induced muscle atrophy through in vivo and in vitro experiments, and to explore whether its mechanism of action is related to the autophagy pathway. SD rats were exposed to hypoxia (12.4% O2). After 4 weeks, the body weight, body composition, wet weight of EDL (extensor digitorum longus) were measured. Muscle fiber morphology was observed; muscle FCSA (fiber cross-sectional area) was calculated, and the function of autophagy differentially expressed genes was analyzed by PCR array. In hypoxic environment, the autophagy inhibitor 3-MA was used to intervene in L6 myotube cells and the protein expressions of SQSTM1/p62 (sequestosome 1), Beclin1 (coiled-coil myosin-like BCL2-interacting protein 1), LC3 (microtubule-associated protein light chain) (key autophagy protein), Myosin (myosin heavy chain), MuRF1 (muscle-specific ring finger 1), Atrogin1 (muscle-specific F-box protein) (muscle atrophy related protein) and the myotube diameter were detected. The results showed that the body weight, lean body mass and its percentage, EDL wet weight and its percentage, FCSA were significantly reduced after hypoxia (P<0.05, P<0.01); The expression of autophagy differential genes in EDL was mainly up-regulated, and the function was mainly enriched in the process of autophagic vesicle formation after hypoxia; the expression of key autophagy and muscle atrophy-related proteins increased, and myotubes diameter decreased in L6 myotube cells after hypoxia, while the expression levels of key autophagy proteins were inhibited, and the degrees of myotube atrophy were relieved after the use of the inhibitor 3-MA under hypoxia (P<0.05). The results showed that hypoxia exposure can lead to muscle atrophy by increasing the level of autophagy, and the activation of the early stage of autophagy played an important role in this process.

CSTR: 32200.14.cjcb.2021.06.0012