PREVENTION OF MUSCLE DISUSE ATROPHY BY MG132 PROTEASOME INHIBITOR

Introduction: Our goal was to determine whether in vivo administration of the proteasome inhibitor MG132 can prevent muscle atrophy caused by hindlimb unloading (HU). Methods: Twenty-seven NMRI mice were assigned to a weight-bearing control, a 6-day HU, or a HU+MG132 (1 mg/kg/48 h) treatment group. Results: Gastrocnemius wasting was significantly less in HU+MG132 mice (-6.7 +/- 2.0%) compared with HU animals (-12.6 +/- 1.1%, P = 0.011). HU was also associated with an increased expression of MuRF-1 (P = 0.006), MAFbx (P = 0.001), and USP28 (P = 0.027) mRNA, whereas Nedd4, E3 alpha, USP19, and UBP45 mRNA did not change significantly. Increases in MuRF-1, MAFbx, and USP28 mRNA were largely repressed after MG132 administration. beta 5 proteasome activity tended to increase in HU (+16.7 +/- 6.1%, P = 0.086). Neither beta 1 and beta 2 proteasome activities nor ubiquitin-conjugated proteins were changed by HU. Conclusions: Our results indicate that in vivo administration of MG132 partially prevents muscle atrophy associated with disuse and highlight an unexpected regulation of MG132 proteasome inhibitor on ubiquitinligases. Muscle Nerve 43: 708-716, 2011