title: AMP-activated kinase α2 deficiency protects mice from denervation-induced skeletal muscle atrophy.
abstract: AMP-activated protein kinase (AMPK) is a master regulator of skeletal muscle metabolic pathways. Recently, AMPK activation by AICAR has been shown to increase myofibrillar protein degradation in C2C12 myotubes via stimulating autophagy and ubiquitin proteasome system. However, the impact of AMPKα on denervation induced muscle atrophy has not been tested. In this study, we performed sciatic denervation on hind limb muscles in both wild type (WT) and AMPKα2(-/-) mice. We found that AMPKα was phosphorylated in atrophic muscles following denervation. In addition, deletion of AMPKα2 significantly attenuated denervation induced skeletal muscle wasting and protein degradation, as evidenced by preserved muscle mass and myofiber area, as well as lower levels of ubiquitinated protein, Atrogin-1 and MuRF-1 expression, and LC3-II/I ratio in tibial anterior (TA) muscles. Interestingly, the phosphorylated FoxO3a at Ser253 was significantly decreased in atrophic TA muscles, which was preserved in AMPKα2(-/-) mice. Collectively, our data support the notion that the activation of AMPKα2 contributes to the atrophic effects of denervation.
authors.affiliation: College of Life Science, University of Chinese Academy of Sciences, Beijing, 100049, China; National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Guo
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Meng
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Yinglong
authors.initials: Y
authors.lastname: Tang
authors.affiliation: College of Life Science, University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wei
authors.affiliation: College of Life Science, University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Run
authors.initials: R
authors.lastname: Feng
authors.affiliation: Department of Cardiovascular Surgery, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Gong
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Huiwen
authors.initials: H
authors.lastname: Wang
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. Electronic address: gj28@ibp.ac.cn.
authors.forename: Guangju
authors.initials: G
authors.lastname: Ji
authors.affiliation: College of Life Science, University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address: luzhongbing@ucas.ac.cn.
authors.forename: Zhongbing
authors.initials: Z
authors.lastname: Lu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009121:Muscle Denervation; D009133:Muscular Atrophy / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control*
chemical_list: C534978:Prkaa2 protein, mouse; D055372:AMP-Activated Protein Kinases
keywords: AMPK; Denervation; Muscle atrophy