Resistance Exercise Increases Muscle Protein Synthesis and Translation of Eukaryotic Initiation Factor 2Bϵ mRNA in a Mammalian Target of Rapamycin-dependent Manner

The contribution of mammalian target of rapamycin (mTOR) signaling to the resistance exercise-induced stimulation of skeletal muscle protein synthesis was assessed by administering rapamycin to Sprague-Dawley rats 2 h prior to a bout of resistance exercise. Animals were sacrificed 16 h postexercise, and gastrocnemius protein synthesis, mTOR signaling, and biomarkers of translation initiation were assessed. Exercise stimulated the rate of protein synthesis; however, this effect was prevented by pretreatment with rapamycin. The stimulation of protein synthesis was mediated by an increase in translation initiation, since exercise caused an increase in polysome aggregation that was abrogated by rapamycin administration. Taken together, the data suggest that the effect of rapamycin was not mediated by reduced phosphorylation of eukaryotic initiation factor 4E (eIF4E) binding protein 1 (BP1), because exercise did not cause a significant change in 4E-BP1(Thr-70) phosphorylation, 4E-BP1-eIF4E association, or eIF4F complex assembly concomitant with increased protein synthetic rates. Alternatively, there was a rapamycin-sensitive decrease in relative eIF2Bepsilon(Ser-535) phosphorylation that was explained by a significant increase in the expression of eIF2Bepsilon protein. The proportion of eIF2Bepsilon mRNA in polysomes was increased following exercise, an effect that was prevented by rapamycin treatment, suggesting that the increase in eIF2Bepsilon protein expression was mediated by an mTOR-dependent increase in translation of the mRNA encoding the protein. The increase in eIF2Bepsilon mRNA translation and protein abundance occurred independent of similar changes in other eIF2B subunits. These data suggest a novel link between mTOR signaling and eIF2Bepsilon mRNA translation that could contribute to the stimulation of protein synthesis following acute resistance exercise.