ИСТИНА

We hypothesized that calpaines can serve an initial link which launches further protein ubiquitination under gravitational unloading of muscle. The aim of our study was to evaluate the role of calpaines in the regulation of muscle protein metabolism during hindlimb unloading: the work of ubiquitin-proteasome as well as protein synthesis (Akt-mTOR-S6K and MAPK/Erk) pathways. For this reason we inhibited µ-calpaines in m.soleus of rats by PD150606 administration during 3-day hindlimb unloading (group UPD, n=7). Gr. U was suspended without treatment, gr.C served as Control (C, n=7). We found that µ-calpain mRNA level did not increase and soleus atrophy was prevented in UPD group (in contrast to U group). mRNA E3 ligase atrogine-1(but not MuRF-1) and conjugated ubiquitin levels did not increase in this group either (as opposed to the U rats). The pFOXO3 content was equal in control and UPD groups as well as the level of eEF2k mRNA expression (in contrast to U group, p<0,05). At the same time nNOS and HSP70 mRNA expression in U soleus was reduced (in comparison to C group,p<0,05). Conclusion: the raise of µ-calpain level under hindlimb suspension leads to the increase of proteins ubiquitination and atrogine-1 level (which represented the ubiquitin-proteasome pathway).The change of μ-calpain level expression is associated with the regulation of protein synthesis, which is controlled not only by Akt-mTOR-S6K signaling pathway, but also by other factors regulating it at the level of elongation.