Inhibition of Proteasomes by Bortezomib Decreases MuRF-1 and MAFbx mRNA Expression in Rat Soleus during Hindlimb Unloading
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Skeletal muscle atrophy caused by unloading is accompanied by increased proteolysis and decreased protein synthesis. It is established that in conditions of muscle unloading, concentration of free amino acids is increased. We hypothesized that proteasome inhibition may decrease amino acid accumulation in skeletal muscle and prevent the atrophy. To test this hypothesis, we treated rats with bortezomib (a proteasome inhibitor) during 7-day hindlimb suspension. Content of key signaling proteins of various signaling pathways was measured by Western-blotting; mRNA level of E3 ligases by RT-PCR, rate of protein synthesis by SUnSET technique. Soleus muscle weight and intensity of the protein synthesis in the groups of “hindlimb suspension” (HS) and “HS + bortezomib” (HSB) were equally reduced as compared to control. Levels of MuRF-1 and MAFbx mRNAs, content of MuRF-1 and calpain-1 proteins, and level of the protein ubiquitination were increased only in the HS group and remained unchanged in the HSB group as compared to the control group. We conclude that inhibition of proteasomes during m. soleus unloading prevents increase in activity of some components of catabolic signaling pathways. However, this is not sufficient to reduce rate of the atrophic processes in skeletal muscle.
Keywords:skeletal muscle atrophy proteasome E3 ubiquitin ligase calpain
The work was supported by the Russian Foundation for Basic Research (project no. 17-04-01838) and by the Program of Basic Researches SSC RF IMPB RAS (project no. 65.3).
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Conflict of interests. The authors declare that they have no conflict of interest.
Statement on the welfare of animals. All procedures were performed in accordance with the European Communities Council Directive (November 24, 1986; 86/609/EEC) and the Declaration on humane treatment of animals. All procedures with the animals were approved by the Biomedicine Ethics Committee of the Institute of Biomedical Problems of the Russian Academy of Sciences/Physiology section of the Russian Bioethics Committee (protocols no. 385, 24.03.2015).
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