title: Mitochondrial Dysfunction Launches Dexamethasone-Induced Skeletal Muscle Atrophy via AMPK/FOXO3 Signaling.
abstract: Muscle atrophy occurs in several pathologic conditions such as diabetes and chronic obstructive pulmonary disease (COPD), as well as after long-term clinical administration of synthesized glucocorticoid, where increased circulating glucocorticoid accounts for the pathogenesis of muscle atrophy. Others and we previously reported mitochondrial dysfunction in muscle atrophy-related conditions and that mitochondria-targeting nutrients efficiently prevent kinds of muscle atrophy. However, whether and how mitochondrial dysfunction involves glucocorticoid-induced muscle atrophy remains unclear. Therefore, in the present study, we measured mitochondrial function in dexamethasone-induced muscle atrophy in vivo and in vitro, and we found that mitochondrial respiration was compromised on the 3rd day following after dexamethasone administration, earlier than the increases of MuRF1 and Fbx32, and dexamethasone-induced loss of mitochondrial components and key mitochondrial dynamics proteins. Furthermore, dexamethasone treatment caused intracellular ATP deprivation and robust AMPK activation, which further activated the FOXO3/Atrogenes pathway. By directly impairing mitochondrial respiration, FCCP leads to similar readouts in C2C12 myotubes as dexamethasone does. On the contrary, resveratrol, a mitochondrial nutrient, efficiently reversed dexamethasone-induced mitochondrial dysfunction and muscle atrophy in both C2C12 myotubes and mice, by improving mitochondrial function and blocking AMPK/FOXO3 signaling. These results indicate that mitochondrial dysfunction acts as a central role in dexamethasone-induced skeletal muscle atrophy and that nutrients or drugs targeting mitochondria might be beneficial in preventing or curing muscle atrophy.
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University , Xi'an 710049, China.|Tianjin Key Laboratory of Exercise Physiology and Sports Medicine, Tianjin University of Sport , Tianjin 300381, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University , Xi'an 710049, China.|Tianjin Key Laboratory of Exercise Physiology and Sports Medicine, Tianjin University of Sport , Tianjin 300381, China.
authors.forename: Yunhua
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University , Xi'an 710049, China.|Tianjin Key Laboratory of Exercise Physiology and Sports Medicine, Tianjin University of Sport , Tianjin 300381, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Wang
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University , Xi'an 710049, China.|Tianjin Key Laboratory of Exercise Physiology and Sports Medicine, Tianjin University of Sport , Tianjin 300381, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University , Xi'an 710049, China.|Tianjin Key Laboratory of Exercise Physiology and Sports Medicine, Tianjin University of Sport , Tianjin 300381, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Qin
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University , Xi'an 710049, China.|Tianjin Key Laboratory of Exercise Physiology and Sports Medicine, Tianjin University of Sport , Tianjin 300381, China.
authors.forename: Le
authors.initials: L
authors.lastname: Shi
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University , Xi'an 710049, China.|Tianjin Key Laboratory of Exercise Physiology and Sports Medicine, Tianjin University of Sport , Tianjin 300381, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University , Xi'an 710049, China.|Tianjin Key Laboratory of Exercise Physiology and Sports Medicine, Tianjin University of Sport , Tianjin 300381, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Cao
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University , Xi'an 710049, China.|Tianjin Key Laboratory of Exercise Physiology and Sports Medicine, Tianjin University of Sport , Tianjin 300381, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University , Xi'an 710049, China.|Tianjin Key Laboratory of Exercise Physiology and Sports Medicine, Tianjin University of Sport , Tianjin 300381, China.
authors.forename: Jiangang
authors.initials: J
authors.lastname: Long
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University , Xi'an 710049, China.|Tianjin Key Laboratory of Exercise Physiology and Sports Medicine, Tianjin University of Sport , Tianjin 300381, China.
authors.forename: Jiankang
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009133:Muscular Atrophy / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism*; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D013267:Stilbenes; D003907:Dexamethasone; D000077185:Resveratrol
keywords: AMPK; Dexamethasone; Mitochondrial dysfunction; Muscle atrophy; Resveratrol