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J Biol Chem, Vol. 274, Issue 31, 21908-21912, July 30, 1999
From the Department of Chemistry and Biochemistry, Neuromuscular
Research Laboratory, Laurentian University, Sudbury, Ontario P3E 2C6,
Canada
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.
Calcineurin Is Required for Skeletal Muscle Hypertrophy
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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V. Horsley and G. K. Pavlath Nfat: ubiquitous regulator of cell differentiation and adaptation J. Cell Biol., March 4, 2002; 156(5): 771 - 774. [Abstract] [Full Text] [PDF]
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E. E. Dupont-Versteegden, M. Knox, C. M. Gurley, J. D. Houle, and C. A. Peterson Maintenance of muscle mass is not dependent on the calcineurin-NFAT pathway Am J Physiol Cell Physiol, June 1, 2002; 282(6): C1387 - C1395. [Abstract] [Full Text] [PDF]
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P. O. Mitchell, S. T. Mills, and G. K. Pavlath Calcineurin differentially regulates maintenance and growth of phenotypically distinct muscles Am J Physiol Cell Physiol, May 1, 2002; 282(5): C984 - C992. [Abstract] [Full Text] [PDF]
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