Related Experiment Videos
Insulin-like growth factor-I and high protein diet decrease calpain-mediated proteolysis in murine muscular dystrophy
M A Wingertzahn1, M M Zdanowicz, A E Slonim
1Department of Pediatrics, North Shore University Hospital-New York University School of Medicine, Manhasset 11030, USA.
Summary
High-protein diet and insulin-like growth factor I reduce muscle wasting in muscular dystrophy mice by decreasing calpain activity. These findings suggest potential therapeutic strategies for human muscular dystrophy.
Area of Science:
- Biochemistry
- Molecular Biology
- Physiology
Background:
- Muscle wasting in muscular dystrophy (MD) is linked to an imbalance between protein synthesis and degradation.
- Key proteolytic pathways in skeletal muscle include lysosomal cathepsin, calcium-dependent calpain, and ATP-dependent ubiquitin pathways.
- Insulin-like growth factor I (IGF-I) and high-protein diets (HPD) have shown promise in reducing muscle proteolysis.
Purpose of the Study:
- To investigate the effects of recombinant human IGF-I (rhIGF-I) and HPD on proteolytic pathways in the skeletal muscle of 129 ReJ dystrophic (dy) mice.
- To determine if rhIGF-I and/or HPD can ameliorate muscle wasting in a mouse model of MD.
- To elucidate the specific proteolytic pathways affected by these treatments.
Main Methods:
- Treatment of 129 ReJ dy mice with rhIGF-I alone or in combination with HPD for 6 weeks.
- Comparison with normal (Norm) nondystrophic (129 J) mice as controls.
- Analysis of net proteolysis, calpain activity, cathepsin B activity, and ubiquitin levels in skeletal muscle.
Main Results:
- Untreated dy mice showed increased net proteolysis, calpain activity, and ubiquitin levels compared to controls.
- Both HPD and rhIGF-I treatments reduced proteolysis in dy mice.
- Reduced proteolysis was associated with decreased calpain-mediated myofibrillar breakdown, potentially due to altered calpain autolysis or increased calpastatin.
- Cathepsin B activity increased with HPD and rhIGF-I + HPD treatments.
- Ubiquitin levels increased in rhIGF-I and rhIGF-I + HPD treated animals.
Conclusions:
- HPD and rhIGF-I effectively decrease proteolysis in the 129 ReJ dy mouse model.
- The observed reduction in muscle wasting is partly attributed to decreased calpain activity.
- These findings suggest that HPD and rhIGF-I may hold therapeutic potential for human MD.