Atrogin-1/MAFbx mRNA expression is regulated by histone deacetylase 1 in rat soleus muscle under hindlimb unloading

Abstract

It is known that MuRF-1 and atrogin-1/MAFbx mRNA expression is increased in rat soleus muscle under unloading conditions. We aimed to determine the role of histone deacetylase 1 (HDAC1) in the activation of MuRF-1 and MAFbx expression in rat soleus muscle at the early stage of hindlimb suspension (HS). To this end, male Wistar rats (195–215 g) were divided into 3 groups (n = 8/group): control (C), 3-day HS (HS) and 3-day HS + HDAC1 inhibitor CI-994 (1 mg/kg/day) (HS + CI). Protein content and mRNA expression levels of regulatory molecules were determined by Western-blotting and RT-PCR. CI-994 treatment prevented HS-induced increase in HDAC1 nuclear content. As expected, 3-day HS induced a significant upregulation in MAFbx, MuRF-1 and ubiquitin. CI-994 administration resulted in an attenuation of HS-mediated increase in MAFbx and ubiquitin expression levels but did not affect MuRF-1 expression. A decrease in histone acetyltransferase p300 nuclear content in the HS group was prevented by CI-994 administration. There were no significant differences in the content of phosphorylated anabolic signaling molecules between HS group and HS + CI group. Thus, inhibition of HDAC1 prevented a HS-mediated increase in MAFbx and ubiquitin expression, but did not affect MuRF-1 gene expression.