The Role of MuRF1 in Glucocorticoid Induced Skeletal Muscle Atrophy

Skeletal muscle atrophy occurs under a variety of conditions and is the result of a shift in the balance of protein turnover from net synthesis towards net degradation. Expression of MuRF1, an E3 ubiquitin ligase, is an excellent marker of muscle atrophy and increases under divergent atrophy‐inducing conditions such as denervation and glucocorticoid treatment. While deletion of MuRF1 has been reported to spare muscle mass following 14 days of denervation (Bodine et al . Science 294:2001), its role in other atrophy conditions is unclear. The goal of this study was to determine whether MuRF1 has a more universal role in regulating muscle atrophy, especially under metabolic disorders. The response of the gastrocnemius (GA) and tibialis anterior (TA) muscles to 14 days of dexamethasone (Dex) treatment (3 mg/kg daily) was examined in 4 month old male and female wild type (WT) and MuRF1 knock out (KO) mice. Following 14 days of Dex, muscle wet weight was significantly decreased in the GA and TA of male and female WT mice. Comparison of WT and KO mice revealed significant sparing of mass in the KO mice of both genders. Further, analysis of fiber cross‐sectional area in the GA showed significant sparing in the KO mice compared to WT. These data reveal that MuRF1 has a significant role in atrophy induced by signals other than disuse. In contrast, analysis of MAFbx KO mice under the same conditions showed no muscle sparing effects. This work was supported by NIH RO1 DK75801.