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Muscle Nerve. 2011 May;43(5):708-16. doi: 10.1002/mus.21949. Epub 2011 Apr 1.

Prevention of muscle disuse atrophy by MG132 proteasome inhibitor.

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  • 1Research Group in Muscle and Exercise Physiology, Institute of Neuroscience, Université Catholique de Louvain, Place Pierre de Coubertin 1, Louvain-la-Neuve B-1348, Belgium.

Abstract

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, E3α, USP19, and UBP45 mRNA did not change significantly. Increases in MuRF-1, MAFbx, and USP28 mRNA were largely repressed after MG132 administration. β5 proteasome activity tended to increase in HU (+16.7 ± 6.1%, P = 0.086). Neither β1 and β2 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 ubiquitin-ligases.

Copyright © 2011 Wiley Periodicals, Inc.

PMID:
21462205
[PubMed - indexed for MEDLINE]
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