title: Calcineurin-mediated slow-type fiber expression and growth in reloading condition.
abstract: OBJECTIVE
  Calcineurin (CaN) signaling pathway has been implicated in the transcriptional regulation of slow muscle fiber genes and in muscle hypertrophy. Our aim was to investigate the functional role of CaN as a regulator of muscle growth and/or muscle fiber type under conditions of recovery from inactivity.
  
  
  METHODS
  Female ICR mice (8 wk of age, 28-32 g) were used. To examine the effects of hindlimb suspension (HS) and reloading on skeletal muscle fiber size and muscle fiber type, animals were designated to 8 wk of HS and subsequent reloading for 4 wk. During reloading, animals were treated with pharmacological inhibitors for CaN (FK506) by intraperitoneal administration (3-5 mg.kg.d). After each experimental period, antigravitational soleus muscle was analyzed.
  
  
  RESULTS
  HS treatment resulted in obvious muscle atrophy and slow-to-fast fiber-type transformation in the soleus muscle. Subsequent reloading for 4 wk following HS induced muscle regrowth and fiber-type reversion toward a slow profile. FK506 administration prevented this kind of reloading-induced transformation of muscle fiber type. Furthermore, it was confirmed that FK506 administration attenuated maintenance of fiber cross-sectional area and reloading-induced fiber regrowth, specifically in slow-type muscle fibers.
  
  
  CONCLUSIONS
  Reloading-induced fiber-type reversion toward a slow profile is prevented by the pharmacological inhibition of CaN. Additionally, inhibition of CaN prevented maintenance and regrowth of slow-type muscle fibers. These results implicate that the CaN signaling pathway is required in the slow-type muscle fiber program under maintenance and suspension-reloading conditions.
authors.affiliation: Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, JAPAN.
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Hitomi
authors.forename: Takako
authors.initials: T
authors.lastname: Kizaki
authors.forename: Hideki
authors.initials: H
authors.lastname: Ohno
authors.forename: Toshihito
authors.initials: T
authors.lastname: Katsumura
authors.forename: Shukoh
authors.initials: S
authors.lastname: Haga
authors.forename: Tohru
authors.initials: T
authors.lastname: Takemasa
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000502:physiology*; D065095:Calcineurin Inhibitors; D005260:Female; D019417:Hindlimb Suspension; D007166:Immunosuppressive Agents / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D024510:Muscle Development / Q000187:drug effects / Q000502:physiology; D018656:Muscle Fibers, Fast-Twitch / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D018657:Muscle Fibers, Slow-Twitch / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000187:drug effects / Q000503:physiopathology / Q000648:ultrastructure; D009133:Muscular Atrophy / Q000473:pathology / Q000503:physiopathology*; D018995:Myosin Heavy Chains / Q000032:analysis; D020033:Protein Isoforms / Q000032:analysis; D020127:Recovery of Function / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D016559:Tacrolimus / Q000494:pharmacology; D016474:Weight-Bearing / Q000502:physiology*
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D020033:Protein Isoforms; D019703:Calcineurin; D018995:Myosin Heavy Chains; D016559:Tacrolimus