Expression and phosphorylation of eukaryotic translation initiation factor 4-gamma (eIF4G) in denervated atrophic and hypertrophic mouse skeletal muscle

Abstract

The eukaryotic translation initiation factor 4-gamma (eIF4G) is important for the initiation of protein synthesis and phosphorylation on S1108 regulates this function of eIF4G. Thus, increased phosphorylation has been reported in conditions associated with increased protein synthesis such as meal feeding and insulin/IGF-1 treatment whereas decreased phosphorylation occurs following starvation, dexamethasone treatment, in sepsis and in atrophic denervated hind-limb muscle. The aim of the present study was to test the hypothesis that S1108 phosphorylation of eIF4G is differentially affected in denervated atrophic hind-limb muscles and denervated hypertrophic hemidiaphragm muscle. Protein expression and phosphorylation in innervated and 6-days denervated atrophic hind-limb muscles (pooled gastrocnemius and soleus) and hypertrophic hemidiaphragms were studied semi-quantitatively using Western blots. Total expression of eIF4G did not change in denervated hind-limb muscles but increased about 77% in denervated hemidiaphragm. S1108 phosphorylated eIF4G decreased about 64% in denervated hind-limb muscles but increased about 1.3-fold in denervated hemidiaphragm. The ratio of S1108 phosphorylated eIF4G to total eIF4G decreased about 60% in denervated hind-limb muscles but no statistically significant change was observed in denervated hemidiaphragm. The differential effect of denervation on eIF4G expression and S1108 phosphorylation in hemidiaphragm (hypertrophic) and hind-limb muscle (atrophic) may represent a regulatory mechanism that helps clarify the differential response of these muscles following denervation.

Keywords: atrophy; denervation; gastrocnemius; hemidiaphragm; hypertrophy; soleus.