2016 年 62 巻 Suppl.1 号 p. 172-178
Objective: The aim of the present study was to investigate the involvement of AMPK in regulating skeletal muscle atrophy during hindlimb unloading.
Methods: Transgenic (AMPK-DN) mice expressing a dominant negative mutant of AMPKα1 in the skeletal muscle and their wild-type littermates (WT) mice were randomly divided into two groups: untreated preexperimental control (n=12/group) and unloading (n=12/group) groups. Mice of the unloading group were subjected to continuous hindlimb suspension for 2 weeks.
Results: Soleus muscle weight relative to body weight in WT mice was decreased by 30% in response to hindlimb suspension, whereas by 20% in AMPK-DN mice. The expressions of ubiquitinated proteins and MuRF1 mRNA, markers of ubiquitin-proteasome system activation, were upregulated by hindlimb suspension in WT mice, but no changes were observed in AMPK-DN mice. The expression of phosphorylated FoxO3a was decreased by hindlimb suspension in WT mice, but not in AMPK-DN mice. HSP72 expression was higher in AMPK-DN mice compared to WT mice during the experiment, and reduced more in WT mice by hindlimb suspension than AMPK-DN mice.
Conclusions: The present study demonstrated that the repression of skeletal muscle AMPK activation suppressed the progress of unloading-induced skeletal muscle atrophy. Our findings suggest that AMPK is involved in adaptation of skeletal muscle mass to atrophic stimuli.
