Calcineurin Is Required for Skeletal Muscle Hypertrophy

Molecular signaling pathways linking increases in skeletal muscle usage to alterations in muscle size have not been identified. In the present study, we tested the hypothesis that calcineurin, a calcium-regulated phosphatase recently implicated in the signaling of some forms of cardiomyopathic growt...

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Bibliographic Details
Published in:The Journal of biological chemistry 1999-07, Vol.274 (31), p.21908-21912
Main Authors: Dunn, Shannon E., Burns, Jennifer L., Michel, Robin N.
Format: Article
Language:English
Subjects:
Animals
Calcineurin - physiology
Calcineurin Inhibitors
Cyclosporine - pharmacology
Gene Expression Regulation - drug effects
Gene Expression Regulation - physiology
Hindlimb
Hypertrophy
Major Histocompatibility Complex
Male
Mice
Muscle Fibers, Fast-Twitch - drug effects
Muscle Fibers, Fast-Twitch - pathology
Muscle Fibers, Fast-Twitch - physiology
Muscle Fibers, Slow-Twitch - drug effects
Muscle Fibers, Slow-Twitch - pathology
Muscle Fibers, Slow-Twitch - physiology
Muscle, Skeletal - drug effects
Muscle, Skeletal - pathology
Muscle, Skeletal - physiology
Myofibrils - drug effects
Myofibrils - physiology
Protein Isoforms - genetics
Signal Transduction - drug effects
Tacrolimus - pharmacology
Transcription, Genetic
Troponin I - genetics
Weight-Bearing
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Summary:Molecular signaling pathways linking increases in skeletal muscle usage to alterations in muscle size have not been identified. In the present study, we tested the hypothesis that calcineurin, a calcium-regulated phosphatase recently implicated in the signaling of some forms of cardiomyopathic growth, is required to induce skeletal muscle hypertrophy and muscle fiber type conversions associated with functional overload in vivo. Administration of the specific calcineurin inhibitors cyclosporin (CsA) or FK506 to mice, for which the fast plantaris muscle was overloaded for 1–4 weeks, prevented the rapid doubling of mass and individual fiber size and the 4–20-fold increase in the number of slow fibers that characterize this condition. CsA treatment influenced the expression of muscle myofibrillar protein genes in a way reflective of fiber phenotype transformations but only in the long term of the overload condition, suggesting that the control of this growth response by calcineurin is not limited to the transcriptional activation of these muscle-specific genes. Clinically, these results provide insight to the post-surgical muscle wasting and weakness observed in recovering transplant recipients administered therapeutic dosages of these immunosuppressants.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.274.31.21908