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The effects of Capn 1 gene inactivation on skeletal muscle growth, development, and atrophy, and the compensatory role of other proteolytic systems

Kemp, C. M., Oliver, W. T., Wheeler, T. L., Chishti, A. H., Koohmaraie, M.
Journal of animal science 2013 v.91 no.7 pp. 3155
DNA, RNA, calpain, caspase-3, caspase-7, cell adhesion, contractile proteins, developmental stages, enzyme activity, gene silencing, genes, genotype, homeostasis, knockout mutants, lipids, mice, muscle development, muscle fibers, muscle protein, muscles, muscular atrophy, protein content, protein synthesis, proteolysis, skeletal muscle
Myofibrillar protein turnover is a key component of muscle growth and degeneration, requiring proteolytic enzymes to degrade the skeletal muscle proteins. The objective of this study was to investigate the role of the calpain proteolytic system in muscle growth development using ?-calpain knockout (KO) mice in comparison to control wild type (WT) mice, and evaluate the subsequent effects of silencing this gene on other proteolytic systems. No differences in muscle development between genotypes were observed during the early stages of growth due to the up-regulation of other proteolytic systems. The KO mice showed significantly higher m-calpain protein levels (P < 0.01) and activity (P < 0.001), and higher caspase 3/7 activity (P < 0.05). At 30 wk of age, KO mice showed increased protein/DNA (P < 0.05) and RNA/DNA ratios (P < 0.01), higher protein content (P < 0.01) at the expense of lipid deposition (P < 0.05), and an increase in size and number of fast-twitch glycolytic muscle fibers (P < 0.05), suggesting that KO mice exhibit an increased capacity to accumulate and maintain protein in their skeletal muscle. Also, expression of proteins associated with muscle regeneration: neural cell adhesion molecule and myoD; were both reduced in the mature KO mice (P < 0.05 and P < 0.01, respectively) indicating less muscle regeneration and, therefore, less muscle damage. These findings indicate the concerted action of proteolytic systems ensure muscle protein homeostasis in vivo. Furthermore, these data contribute to the existing evidence of the importance of the calpain systems involvement in muscle growth, development, and atrophy. Collectively, these data suggest that there are opportunities to target the calpain system to promote the growth and(or) restoration of skeletal muscle mass.