Effect of enhanced muscle tone on the expression of atrogenes and cytoskeletal proteins during postural muscle unloading

Abstract

Skeletal muscle unloading leads to the decreased electrical activity and decline of muscle tone.

Aims: Current study evaluated the effect of muscle tone preservation achieved by tetanus toxin (TeNT) treatment on signaling pathways regulating atrophic processes during unloading.

Main methods: Four groups of rats were used: non-treated control (C), control rats with TeNT administration (CT), 7 days of unloading/hindlimb suspension with placebo (HS), and 7 days of unloading with TeNT administration (HST).

Key findings: Absolute and relative force of tetanic contractions was decreased by 65% in soleus muscle of HS rats when compared with C. Treatment with TeNT significantly lessened force decline in soleus muscle of HST rats when compared with HS. TeNT administration increased myosin heavy chain I beta (MyHC Iβ) expression in CT rats and prevented MyHC Iβ loss in HST group when compared with C rats. Desmin content was lower by 31.4% (p < 0.05) in HS group when compared with HST. Calpain-1 expression was increased in HS group when compared with C, CT and HST. There was a decrease in p-p70S6K content (41%, p < 0,05) and an increase in p-eEF2 content (77%, p < 0,05) in HS group when compared with C, while there were no significant differences in the content of these proteins between HST, CT and C groups.

Significance: Treatment with TeNT significantly diminished unloading-induced decline of soleus muscle mass and mechanical properties and affected the regulation of MyHC Iβ expression. These effects are mediated by signaling pathways regulating protein synthesis and degradation.

Keywords: Calpain-1; Desmin; MAFbx; MuRF1; Muscle tone; Muscle unloading; Myosin heavy chain.