Mechanical and signaling responses of unloaded rat soleus muscle to chronically elevated β-myosin activity.

Autor: Sergeeva KV; Institute of Biomedical Problems of the Russian Academy of Sciences, Moscow, Russia. Electronic address: sergeeva_xenia@mail.ru., Tyganov SA; Institute of Biomedical Problems of the Russian Academy of Sciences, Moscow, Russia., Zaripova KA; Institute of Biomedical Problems of the Russian Academy of Sciences, Moscow, Russia., Bokov RO; Institute of Biomedical Problems of the Russian Academy of Sciences, Moscow, Russia., Nikitina LV; Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Sciences, Ekaterinburg, Russia., Konstantinova TS; Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Moscow, Russia., Kalamkarov GR; Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Moscow, Russia., Shenkman BS; Institute of Biomedical Problems of the Russian Academy of Sciences, Moscow, Russia.
Jazyk: angličtina
Zdroj: Archives of biochemistry and biophysics [Arch Biochem Biophys] 2024 Apr; Vol. 754, pp. 109961. Date of Electronic Publication: 2024 Mar 14.
DOI: 10.1016/j.abb.2024.109961
Abstrakt: It has been reported that muscle functional unloading is accompanied by an increase in motoneuronal excitability despite the elimination of afferent input. Thus, we hypothesized that pharmacological potentiation of spontaneous contractile soleus muscle activity during hindlimb unloading could activate anabolic signaling pathways and prevent the loss of muscle mass and strength. To investigate these aspects and underlying molecular mechanisms, we used β-myosin allosteric effector Omecamtiv Mekarbil (OM). We found that OM partially prevented the loss of isometric strength and intrinsic stiffness of the soleus muscle after two weeks of disuse. Notably, OM was able to attenuate the unloading-induced decrease in the rate of muscle protein synthesis (MPS). At the same time, the use of drug neither prevented the reduction in the markers of translational capacity (18S and 28S rRNA) nor activation of the ubiquitin-proteosomal system, which is evidenced by a decrease in the cross-sectional area of fast and slow muscle fibers. These results suggest that chemically-induced increase in low-intensity spontaneous contractions of the soleus muscle during functional unloading creates prerequisites for protein synthesis. At the same time, it should be assumed that the use of OM is advisable with pharmacological drugs that inhibit the expression of ubiquitin ligases.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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