Regulation of myogenin protein expression in denervated muscles from young and old rats

Myogenin is a muscle-specific transcription factor participating in denervation-induced increases in nicotinic ACh receptor (nAChR) gene expression. Although myogenin RNA expression in denervated muscle is well documented, surprisingly little is known about myogenin protein expression. Therefore, we assayed myogenin protein and RNA in innervated and denervated muscles from young (4 mo) and old (24-32 mo) rats and compared this expression to that of the nAChR alpha-subunit RNA. These assays revealed increased myogenin protein expression within 1 day of denervation, preceding detectable increases in nAChR RNA. By 3 days of denervation, myogenin and nAChR alpha-subunit RNA were increased 500- and 130-fold, respectively, whereas myogenin protein increased 14-fold. Interestingly, old rats (32 mo) had 6-fold higher myogenin protein and approximately 80-fold higher mRNA levels than young rats. However, after denervation, expression levels were similar for young and old animals. The increased myogenin expression during aging, which tends to localize to small fibers, likely reflects spontaneous denervation and/or regeneration. Our results show that increased myogenin protein in denervated muscles correlates with the upregulation of its mRNA.