The aim of this study was to improve our understanding and the current treatment of
denervation-induced skeletal muscle
atrophy. We used isobaric tags for relative and absolute quantification (iTRAQ) coupled with two-dimensional liquid chromatography-tandem mass spectrometry (2D LC-MS/MS) to identify the differentially expressed
proteins in the tibialis anterior (TA) muscle of rats at 1 and 4 weeks following sciatic nerve transection. A total of 110
proteins was differentially expressed and was further classified using terms from the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases to unravel their molecular functions. Among the differentially expressed metabolic
enzymes involved in glycolysis, Krebs cycle and oxidative phosphorylation, α- and β-
enolase displayed an increased and decreased expression, respectively, which was further validated by western blot analysis and immunohistochemistry. These findings suggest that the
enolase isozymic switch during
denervation-induced
muscle atrophy is the reverse of that occurring during muscle maturation. Notably, protein‑protein interaction analysis using the STRING database indicated that the
protein expression of
tumor necrosis factor receptor-associated factor-6 (
TRAF6), muscle ring-finger
protein 1 (MuRF1) and
muscle atrophy F-box (MAFBx) was also upregulated during denervation‑induced skeletal muscle
atrophy, which was confirmed by western blot analysis.
TRAF6 knockdown experiments in L6 myotubes suggested that the decreased expression of
TRAF6 attenuated glucocorticoid‑induced myotube
atrophy. Therefore, we hypothesized that the upregulation of
TRAF6 may be involved in the development of denervation‑induced
muscle atrophy, at least in part, by regulating the expression of MAFBx and MuRF1
proteins. The data from the present study provide valuable insight into the molecular mechanisms regulating
denervation-induced
muscle atrophy.