Key Anabolic Markers in Human M. Soleus after 21-Day Head-Down Tilt Bedrest

Abstract

Prolonged bed rest can have a significant negative effect on skeletal muscle, leading to muscle wasting and reduced strength. This process can occur in as little as 10 days in healthy individuals, with the loss of muscle mass and strength being particularly pronounced during the first week of immobilization. Head-down tilt bed rest (HDT) is a method used to simulate the physiological changes that occur in weightlessness during spaceflight. This technique involves lying in bed with the head tilted downward. This paper is dedicated to the analysis of key anabolic markers of the soleus muscle during 21 days of HDT BR. The HDT BR experiment was conducted at the Institute of Biomedical Problems, Russian Academy of Sciences. Six healthy male volunteers, aged 25–35 years, were subjected to 21 days of strict bed rest with a tilt angle of –6°. A needle biopsy of the m.soleus was performed using the Bergström method before the start of HDT BR and on day 21 of HDT BR. The biopsy material was immediately frozen in liquid nitrogen for further Western blot and PCR analysis. Examination of mTORC1 substrates showed a significant decrease in p70 and 4EBP1 phosphorylation after HDT BR. We also observed a significant decrease in the phosphorylation of another ribosomal kinase, p90RSK, a significant increase in eEF2 phosphorylation and an increase in eEF2k mRNA expression. In addition, the phosphorylation of AMPK and its substrate ACC decreased after HDT BR. The data obtained in this work support the hypothesis that a decrease in protein synthesis, together with an increase in proteolysis, contributes to the development of human m. soleus atrophy after 21 days of HDT BR.