title: Maintenance of muscle mass is not dependent on the calcineurin-NFAT pathway.
abstract: In this study, the role of the calcineurin pathway in skeletal muscle atrophy and atrophy-reducing interventions was investigated in rat soleus muscles. Because calcineurin has been suggested to be involved in skeletal and cardiac muscle hypertrophy, we hypothesized that blocking calcineurin activity would eliminate beneficial effects of interventions that maintain muscle mass in the face of atrophy-inducing stimuli. Hindlimb suspension and spinal cord transection were used to induce atrophy, and intermittent reloading and exercise were used to reduce atrophy. Cyclosporin (CsA, 25 mg x kg(-1) x day(-1)) was administered to block calcineurin activity. Soleus muscles were studied 14 days after the onset of atrophy. CsA administration did not inhibit the beneficial effects of the two muscle-maintaining interventions, nor did it change muscle mass in control or atrophied muscles, suggesting that calcineurin does not play a role in regulating muscle size during atrophy. However, calcineurin abundance was increased in atrophied soleus muscles, and this was associated with nuclear localization of NFATc1 (a nuclear factor of activated T cells). Therefore, results suggest that calcineurin may be playing opposing roles during skeletal muscle atrophy and under muscle mass-maintaining conditions.
authors: Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA. dupontesthere@uams.edu
authors: Esther E
authors: EE
authors: Dupont-Versteegden
authors: Micheal
authors: M
authors: Knox
authors: Cathy M
authors: CM
authors: Gurley
authors: John D
authors: JD
authors: Houlé
authors: Charlotte A
authors: CA
authors: Peterson
mesh_terms: D000818:Animals; D001284:Atrophy / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D019771:Axotomy; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism*; D065095:Calcineurin Inhibitors; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D016572:Cyclosporine / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005081:Exercise Therapy; D005260:Female; D019417:Hindlimb Suspension; D064326:MEF2 Transcription Factors; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology*; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000378:metabolism; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D013116:Spinal Cord / Q000503:physiopathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D065095:Calcineurin Inhibitors; D004268:DNA-Binding Proteins; D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D016572:Cyclosporine; D019703:Calcineurin