Three days of unloading induces pre‐translational changes in human skeletal muscle

Abstract

Any change in skeletal muscle mass is controlled by the balance of protein synthesis and degradation. These processes require signalling through the PI3K‐Akt‐mTOR and ubiquitin‐proteasome pathways. This study explored whether these pathways are activated soon after withdrawal of weight bearing. Muscle biopsies were obtained from m. vastus lateralis and m. soleus, of eight healthy men prior to and following three days unilateral lower limb suspension (ULLS). mRNA levels of IGF1, Caspase‐3, Calpain‐2, Foxo1A, Foxo3A, Atrogin‐1, MuRF‐1, 4E‐BP1, and Myostatin were quantified in combination with protein measurements of Akt, Foxo 1 and 3, p38 and mTOR. Caspase‐3, Calpain‐2, Atrogin‐1, MuRF‐1 and 4E‐BP1 mRNA increased after ULLS in m vastus lateralis but not in m soleus. Myostatin increased in both muscles and to a greater extent in m. soleus. Total amounts and phosphorylation of Akt, Foxo1 and 3, p38 and mTOR were unaltered (p>0.05). These results suggest that Caspase‐3, Calpain‐2, Atrogin1, MuRF1, 4E‐BP1 and Myostatin are pretranslational regulated in human skeletal muscle within three days of ULLS. Given that neither of measured signalling pathways was altered, it appears that other pathways stimulated the transcription of Atrogin1 and MuRF1. The difference in the gene expression pattern across m soleus and m vastus lateralis muscles indicates the atrophy mechanism may be different in the two muscle types.