BLOCKING OF RYANODINE RECEPTOR OXIDATION PREVENTS GROWTH OF PROTEOLYSIS MARKERS AND DECREASE OF PROTEIN SYNTHESIS PARAMETERS FOLLOWING 7-DAY HINDLIMB SUSPENSION IN RATS

Real and modeled microgravity fairly rapidly causes atrophy of muscular fibers that has a negative effect on the muscle functioning. Atrophy is an outcome of decreased synthesis of protein and activation of proteolytic mechanisms. However, we still lack full understanding of how microgravity contributes to these changes. One of the early molecular changes in the skeletal muscle under modeled microgravity is accumulation of Ca ions in myoplasm which, according to literary data, may be responsible for extent changes in molecular regulation as on the level of gene expression, so the activity of enzymic cascades. We hypothesized that drug S-107 that prevents oxidation and super-activation of ryanodine receptors would normalize Ca exchange and balance of protein synthesis and decay in postural m. soleus during 7-d hindlimb suspension in Wistar rats. The animals were divided into 3 groups: control (С), 7-day suspension (7HS) and 7-day suspension and feeding S-107 at a dose of 50 mg|1 kg of body mass (7HSS). In 7HS, we observed considerable decreases of the soleus mass index and absolute muscle mass, reductions of ribosomal RNA РНК 18S and 28S and growth in expression of mRNA ubiquitin E3 ligases Atrogin-1 and MuRF-1. In group 7HSS, all these changes were fully or partly prevented, excluding growth of Atrogin-1 expression and loss in absolute muscle mass evidencing for the role of oxidation and excessive activation of ryanodine receptors in m. soleus atrophy due to the modeled microgravity.