title: Involvement of AMPK in regulating slow-twitch muscle atrophy during hindlimb unloading in mice.
abstract: AMPK is considered to have a role in regulating skeletal muscle mass. However, there are no studies investigating the function of AMPK in modulating skeletal muscle mass during atrophic conditions. In the present study, we investigated the difference in unloading-associated muscle atrophy and molecular functions in response to 2-wk hindlimb suspension between transgenic mice overexpressing the dominant-negative mutant of AMPK (AMPK-DN) and their wild-type (WT) littermates. Male WT (n = 24) and AMPK-DN (n = 24) mice were randomly divided into two groups: an untreated preexperimental control group (n = 12 in each group) and an unloading (n = 12 in each group) group. The relative soleus muscle weight and fiber cross-sectional area to body weight were decreased by ∼30% in WT mice by hindlimb unloading and by ∼20% in AMPK-DN mice. There were no changes in puromycin-labeled protein or Akt/70-kDa ribosomal S6 kinase signaling, the indicators of protein synthesis. The expressions of ubiquitinated proteins and muscle RING finger 1 mRNA and protein, markers of the ubiquitin-proteasome system, were increased by hindlimb unloading in WT mice but not in AMPK-DN mice. The expressions of molecules related to the protein degradation system, phosphorylated forkhead box class O3a, inhibitor of κBα, microRNA (miR)-1, and miR-23a, were decreased only in WT mice in response to hindlimb unloading, and 72-kDa heat shock protein expression was higher in AMPK-DN mice than in WT mice. These results imply that AMPK partially regulates unloading-induced atrophy of slow-twitch muscle possibly through modulation of the protein degradation system, especially the ubiquitin-proteasome system.
authors.affiliation: Department of Physiology, Graduate School of Health Sciences, Toyohashi SOZO University, Toyohashi, Aichi, Japan;
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Egawa
authors.affiliation: Department of Physiology, Graduate School of Health Sciences, Toyohashi SOZO University, Toyohashi, Aichi, Japan; Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto, Japan;
authors.forename: Ayumi
authors.initials: A
authors.lastname: Goto
authors.affiliation: Laboratory of Physiology, School of Health Sciences, Toyohashi SOZO University, Toyohashi, Aichi, Japan;
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Ohno
authors.affiliation: Laboratory of Physiology, School of Health Sciences, Toyohashi SOZO University, Toyohashi, Aichi, Japan;
authors.forename: Shingo
authors.initials: S
authors.lastname: Yokoyama
authors.affiliation: Department of Physiology, Graduate School of Health Sciences, Toyohashi SOZO University, Toyohashi, Aichi, Japan;
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ikuta
authors.affiliation: Department of Physiology, Graduate School of Health Sciences, Toyohashi SOZO University, Toyohashi, Aichi, Japan;
authors.forename: Miho
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Department of Exercise and Sports Physiology, Faculty of Education, Yamaguchi University, Yamaguchi, Japan;
authors.forename: Takao
authors.initials: T
authors.lastname: Sugiura
authors.affiliation: Graduate School of Health and Sports Science, Doshisha University, Kyotanabe, Kyoto, Japan; and.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Ohira
authors.affiliation: Hirosaki Gakuin University, Hirosaki, Aomori, Japan.
authors.forename: Toshitada
authors.initials: T
authors.lastname: Yoshioka
authors.affiliation: Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto, Japan;
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Department of Physiology, Graduate School of Health Sciences, Toyohashi SOZO University, Toyohashi, Aichi, Japan; gotok@sepia.ocn.ne.jp.
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Goto
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000502:physiology*; D000818:Animals; D003345:Corticosterone / Q000097:blood; D005799:Genes, Dominant; D019417:Hindlimb Suspension; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism / Q000473:pathology*; D009133:Muscular Atrophy / Q000097:blood / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D009929:Organ Size / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis
chemical_list: D055372:AMP-Activated Protein Kinases; D046988:Proteasome Endopeptidase Complex; D003345:Corticosterone
keywords: AMP-activated protein kinase; autophagy; heat shock protein; microRNA; protein degradation; ubiquitin-proteasome