Calcineurin differentially regulates maintenance and growth of phenotypically distinct muscles.
Adequate muscle mass is critical for human health. The molecular pathways regulating maintenance and growth of adult skeletal muscle are little understood. Calcineurin (CN) is implicated as a key signaling molecule in hypertrophy. Whether CN is involved in all forms of muscle growth or in different muscles is unknown. Here, we examine the role of CN in regulating maintenance of muscle size and growth of atrophied muscle in the soleus (slow) and plantaris (fast). The CN inhibitor cyclosporin A (CsA) differentially affects muscle growth and maintenance depending on muscle phenotype. The plantaris is more severely affected by CsA than the soleus in both growth conditions. One-week vs. 2-wk CsA treatment suggests that both CN-dependent and CN-independent growth occur in the atrophied soleus, whereas plantaris growth appears to be totally CN dependent. Our results suggest that CN regulates multiple types of muscle growth, depending both on muscle phenotype and stage of myofiber growth. Differential expression of components of the CN pathway occurs and may contribute to the differences between muscles.
Mitchell
Patrick O
PO
Department of Pharmacology and Graduate Program in Cell and Developmental Biology, Emory University, Atlanta, Georgia 30322, USA.
Mills
Stephen T
ST
Pavlath
Grace K
GK
D000818:Animals; D019703:Calcineurin / Q000378:metabolism*; D065095:Calcineurin Inhibitors; D021983:Cyclophilins / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology*; D005260:Female; D019417:Hindlimb Suspension; D006801:Humans; D006984:Hypertrophy / Q000503:physiopathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism; D009133:Muscular Atrophy / Q000503:physiopathology; D019696:Peptidylprolyl Isomerase; D010641:Phenotype; D011897:Random Allocation; D015398:Signal Transduction / Q000502:physiology
D065095:Calcineurin Inhibitors; C081786:cyclophilin B; D016572:Cyclosporine; D019703:Calcineurin; D021983:Cyclophilins; D019696:Peptidylprolyl Isomerase