ABSTRACT

　It is known that muscle mass is determined by the balance between protein synthesis and protein degradation. The ubiquitin-proteasome pathway is a major route of protein degradation. Recently, we reported that the muscle-specific deletion of a crucial proteasomal gene, Rpt3, in mice induced the muscle loss in mice. The purpose of present study was to clarify the metabolomic profile in skeletal muscle of musclespecific proteasome dysfunction mice.
　We crossed the Rpt3 floxed mice with a transgenic line expressing Cre recombinase under the control of a myosin light chain 1 fast promoter to generate muscle-specific Rpt3-knockout mice (KO mice). We evaluated the metabolomic profile in the skeletal muscle of control mice and KO mice by using the metabolome analysis. The appearance of skeletal muscle of KO mice was distinct from those of control mice. The absolute weights of the tibialis anterior, gastrocnemius and soleus muscles were smaller in KO mice (p<0.05). In the metabolome analyses of the 112 metabolites, 64 metabolites were significance in skeletal muscle of KO mice compared to control mice (p<0.05). These results suggest that muscle-specific proteasome dysfunction may induce metabolic disorders in the skeletal muscle. These findings will contribute to further clarify the molecular mechanisms of muscle atrophy.

DESCENTE SPORTS SCIENCE Vol.37/THE DESCENTE AND ISHIMOTO MEMORIAL FOUNDATION FOR THE PROMOTION SPORTS SCIENCE