Submitted to: Journal of Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 25, 2013
Publication Date: July 1, 2013
Repository URL: http://handle.nal.usda.gov/10113/56939
Citation: Kemp, C.M., Oliver, W.T., Wheeler, T.L., Chishti, A.H., Koohmaraie, M. 2013. The effects of Capn1 gene inactivation on skeletal muscle growth, development, and atrophy, and the compensatory role of other proteolytic systems. Journal of Animal Science. 91(7):3155-3167. Interpretive Summary: Protein turnover is an essential component of muscle growth and development, requiring proteolytic enzymes such as µ-calpain to degrade skeletal muscle proteins so they can be replaced with new proteins. The objective of this study was to determine the difference in muscle growth and development of normal mice and those deficient in µ-calpain. We have shown that there were no differences in body or muscle mass between control mice and mice deficient in the enzyme µ-calpain, during the early growth and development phase. However, during this period, other enzymes were up-regulated to compensate for the lack of µ-calpain which provides an explanation for the lack of difference in muscle growth. These results highlight the interaction and cross-talk between muscle enzyme systems and their importance in muscle growth.
Technical Abstract: 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 µ-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.