Skeletal muscle is composed of two types of muscle fiber, slow and fast, which have different capabilities -- slow fibers do not tire easily and are high endurance, whereas fast fibers tire easily and are low endurance.
The relative amount of each fiber type is determined by muscle usage -- exercise training causes fast fibers to become slow fibers, whereas inactivity that results in muscle atrophy (for example inactivity induced by spinal cord injury and unloading caused by space flight or tail suspension) causes slow fibers to become fast fibers.
Two studies in mice appearing in the November issue of the Journal of Clinical Investigation have provided insight into the molecular mechanisms that regulate muscle function. As discussed in the accompanying commentary by David Glass from Novartis Institutes for BioMedical Research, these two studies provide much fodder for researchers looking to develop new therapeutics for the treatment of skeletal muscle diseases.
Eric Olson and colleagues from the University of Texas Southwestern Medical Center, Dallas, showed that in mice, proteins known as class II HDACs repress the activity of MEF2, which is required for the expression of genes that cause muscle fibers to be slow fibers. Furthermore, in slow fibers, class II HDACs were degraded by the ubiquitin proteasome system such that slow fiber identity was maintained.
In the second study, Shin'ichi Takeda and colleagues from the National Center of Neurology and Psychiatry, Tokyo, showed that in mice, one mechanism by which tail suspension causes muscle atrophy is that it alters the function of a protein known as nNOS, which leads to the activation of Foxo3a, which, in turn, upregulates the expression of various atrophy-related genes. Importantly, pharmacological inhibition of nNOS attenuated muscle atrophy in the mice.
Article: Histone deacetylase degradation and MEF2 activation promote the formation of slow-twitch myofibers
Materials provided by Journal of Clinical Investigation. Note: Content may be edited for style and length.
Cite This Page: