Disuse-induced nuclear accumulation of histone deacetylase 4 in rat skeletal muscle

Abstract

Skeletal muscle wasting induced by prolonged periods of muscle disuse due to immobilization, chronic bed rest, physical inactivity, or spaceflight causes dramatic muscle atrophy via multiple signaling pathways. However, the molecular mechanisms of muscle wasting are not completely understood. Histone deacetylase (HDAC) 4 is a central component of muscle transcriptional reprogramming upon denervation. We recently examined the changes in the nuclear expression of HDAC4 and its downstream targets in immobilization-induced rat skeletal muscle atrophy. Nuclear abundance of HDAC4 was found to enhance the transcription of myogenin and MyoD , muscle-specific transcriptional regulators, and induce the expression of atrogin-1, a central component of muscle atrophy. These data demonstrated that the cellular localization of HDAC4 and downstream proteins may play an important role in disuse-induced rat skeletal muscle atrophy.