title: Intermittent reloading attenuates muscle atrophy through modulating Akt/mTOR pathway.
abstract: OBJECTIVE
  The aim of this study is to investigate the effects of intermittent reloading during hindlimb unloading (HU) on the changes in intracellular signaling pathways in skeletal muscle.
  
  
  METHODS
  Male Wister rats were divided randomly into one of three experimental groups: 1) nonsuspended control, 2) HU for 7 d, and 3) HU with intermittent reloading (HU/IR) for 4 h.d(-1). After each experimental period, the antigravitational soleus muscle was analyzed.
  
  
  RESULTS
  After 7 d of HU treatment, muscle fiber atrophy (decrease in relative muscle mass: 0.28 mg.g(-1) in the HU group vs 0.36 mg.g(-1) in the control group, P < 0.05; decrease in fiber CSA: 1682.6 microm2 in the HU group vs 2673.0 microm2 in the control group, P < 0.05) and a decrease in phosphorylation levels of anabolic signaling pathway (Akt and mTOR) were observed. Additionally, expressions of two types of muscle-specific E3 ubiquitin ligase mRNA (muscle atrophy F-box (MAFbx), and muscle ring finger 1 (MuRF1)) were upregulated during muscle atrophy. Increases in binding activities of nuclear factor kappa B (NFkappaB) were also determined. In contrast, IR treatment attenuated the muscle fiber atrophy (0.33 mg.g(-1) and 2067.5 microm2) and partially increased the phosphorylation levels of anabolic signaling molecules. Expression of MAFbx and MuRF1 mRNA were returned to the control level, and binding activities of nuclear NFkappaB was suppressed with the effects of IR.
  
  
  CONCLUSIONS
  These results suggest that IR-induced attenuation of skeletal muscle atrophy is achieved by the synergy between increased anabolic and decreased catabolic signaling mechanisms.
authors.affiliation: Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY, USA.
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Miho
authors.initials: M
authors.lastname: Noguchi
authors.forename: Tohru
authors.initials: T
authors.lastname: Takemasa
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology*; D009133:Muscular Atrophy / Q000378:metabolism* / Q000503:physiopathology*; D011494:Protein Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases
chemical_list: D011494:Protein Kinases; C546845:mTOR protein, rat; C494920:Akt1 protein, rat; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases