Insulin-Like Growth Factor-I and High Protein Diet Decrease Calpain-Mediated Proteolysis in Murine Muscular Dystrophy

Mark A. Wingertzahn, Martin M. Zdanowicz, Alfred E. Slonim

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


In muscular dystrophy (MD) the imbalance between muscle protein synthesis and degradation may be an important factor leading to muscle wasting. The three major pathways of muscle proteolysis identified in skeletal muscle are: the lysosomal cathepsin pathway, the calcium-dependent calpain pathway, and the ATP-dependent ubiquitin pathway. Insulin-like growth factor I (IGF-I) and a high-protein diet (HPD) have been shown to reduce proteolysis in skeletal muscle. We examined the effect of 6 weeks of recombinant human IGF-I (rhIGF-I) alone or in combination with HPD treatment on the proteolytic pathways in skeletal muscle of 129 ReJ dystrophic (dy) mice. (A group of normal (Norm) nondystrophic (129 J) mice were Included as controls). Untreated dy mice exhibited increased net proteolysis (P < 0.05), elevated net calpain activity (P < 0.01), and increased ubiquitin levels when compared to control mice (P < 0.05). Our evidence suggests that HPD and rhIGF-I decrease proteolysis in the 129 ReJ dy mouse. This effect appears attributable, at least in part, to reduced calpain-mediated myofibrillar breakdown (P < 0.05) due to decreased calpain autolysis or increased calpastatin levels. In contrast to calpain, cathepsin B activity was increased in HPD and rhIGF-I + HPD-treated dy muscle (P < 0.05) and unaltered in the rhIGF-I treated animals. Levels of free and protein-conjugated ubiquitin were also increased in rhIGF-I, and rhIGF-I + HPD treated dy animals (P < 0.05). The amelioration of muscle wasting in the 129 ReJ dy model by HPD and/or rhIGF-I may have potential implications in the treatment of human MD.

Original languageEnglish (US)
Pages (from-to)244-250
Number of pages7
JournalExperimental Biology and Medicine
Issue number3
StatePublished - 1998
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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