Expression of e3-ubiquitin ligases murf-1 and mafbx in human postural and locomotor muscles during head-down hypokinesia

Functional unloading of skeletal muscles enhances proteasome degradation in which the key role is played by Е3-ligases atrogin-1/MAFbx and MuRF-1. Their expression starts growing on the first day of unloading. There is actually little literature on expression of ubiquitin ligases in dry immersion or bedrest. Our purpose was to investigate MuRF-1 and MAFbx expression and control in postural m. soleus and locomotor m. vastus lateralis during a 21-day bedrest study. The observed reduction of cross-section areas in slow fibers of m. soleus and m. vastus lateralis was accompanied by activation of MuRF-1 and MAFbx in m. soleus and MAFbx in m. vastus lateralis, respectively. The investigation of E3 ligases signal pathways showed an increased expression of myogenin and IL-6 receptors in both muscles, whereas transcriptional activation of FoxO3 was seen in m. soleus only. These results suggest elevated expression of Е3-ubiquitin ligases MuRF-1 and MAFbx in m. soleus and MAFbx in m. vastus lateralis, as well as their key signal pathways in bedrested human subjects. Also, our findings argue against the previously stated notion that degradation of protein has no influence on skeletal muscles atrophy due to hypokinesia.