{Reference Type}: Journal Article
{Title}: Mechanical and signaling responses of unloaded rat soleus muscle to chronically elevated β-myosin activity.
{Author}: Sergeeva KV;Tyganov SA;Zaripova KA;Bokov RO;Nikitina LV;Konstantinova TS;Kalamkarov GR;Shenkman BS;
{Journal}: Arch Biochem Biophys
{Volume}: 754
{Issue}: 0
{Year}: 2024 Apr 14
{Factor}: 4.114
{DOI}: 10.1016/j.abb.2024.109961
{Abstract}: 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.