EFFECT OF PROTEASOME INHIBITOR MG-132 ON MUSCLE DISUSE ATROPHY

Abstract

The purpose of this study was to evaluate whether administration of a proteasome inhibitor (MG-132) in vivo is able to prevent muscle atrophy caused by hindlimb unloading (HU). Twenty-seven NMRI mice were assigned to a weight-bearing control, a 6-day HU or a 6-day HU+MG-132 (1mg/kg/48h) treatment group. Soleus (SOL), gastrocnemius (GAS) and tibialis anterior (TA) muscles were removed and weighed. After HU muscle wasting was 20% in SOL, 7% in TA and 13% in GAS (P<0.05). MG-132 treatment prevented 50% of atrophy induced by HU in GAS only (P<0.05). In this muscle, HU was associated with an increased expression of MuRF-1 (P<0.05), Atrogin-1 (P<0.05) and myostatin mRNA (P<0.055), whereas E3α, Nedd-4 and IL-6 remained unchanged. A 19% increase in chymotrypsin-like proteasomal activity was observed in HU (P<0.05) but not in HU+MG-132 GAS. Interestingly, a repression of MurF-1 and myostatin mRNA was also observed with MG-132. In TA, pro-caspase-3 cytosolic expression was decreased by 60% with HU (P<0.05) and only by 20% with HU+MG-132 (P<0.05). These results suggest that in vivo administration of MG-132 can prevent partially muscle atrophy associated with disuse, but that this effect is not specific of a proteasome activity inhibition