The Early Mtor Signaling Responses To Resistance Exercise Stimuli In Skeletal Muscle In Well-trained Athletes

Abstract

INTRODUCTION: Muscle contractile activity associated with physical exercise stimulates multiple signaling pathways and induces transient changes in gene transcription. The bulk of skeletal muscle is regulated by the control of hypertrophy (anabolic) and atrophy (catabolic) processes. Muscle protein synthesis (MPS) is stimulated, while a small suppression of muscle protein breakdown (MPB) occurs, such that protein balance becomes positive (MPS > MPB). Recently several line of studies has been focused on the role played by the mammalian target of rapamycin (mTOR) signal pathway, i.e., activation of mTOR and its downstream signaling proteins p70 ribosomal protein S6 kinase (p70S6k) and eukaryotic initiation factor (eIF) 4E-binding protein (4E-BP1), in regulating translation initiation to syntheses of muscle protein. Furthermore, more recent work has shown that artificial activation of AMPK suppresses muscle protein synthesis by inhibiting the mTOR signaling pathway. Therefore, we hypothesized that the cellular mechanism for the decrease in muscle protein synthesis during an acute bout of resistance exercise in humans would be associated with an activation of AMPK in addition to an inhibition of the downstream components of the mTOR signaling pathway (4E-BP1 Thr37/46 and S6K1 Thr421/Ser424). METHODS: Eight healthy elite male (n=4) and female (n=4) athletes (22.8±1yrs) performed 10 sets of 10 leg extensions at 60°deg/sec. Muscle biopsies were taken from the vastus lateralis at rest, and 30 s after stopping the exercise. Western blotting with phosphospecific and pan antibodies was used to determine the phosphorylation status of AMPK, 4E-BP1, mTOR, and p70S6k. Blood samples were analysed for serum estradiol(E2), testosterone, insulin, GH and IGF- 1. RESULTS: The phosphorylation states of p70S6k on Thr421/Ser424 and AMPK on Thr172 were increased by 137% and 27% (p<.05). However, high intensity of resistance exercise did not induce any significant changes in mTOR and 4E-BP1 phosphorylations after acute exercise. In addition, estradiol(E2) and growth hormone were increased by 21% (p<.05) and 1784% (p<.001), whereas insulin was decreased by 112% (p<.05) after exercise. CONCLUSION: The present study demonstrates that resistance exercise increases AMPK activity and inhibit mTOR, 4E-BP1 phosphorylation and protein synthesis in human skeletal muscle. Thus, we postulated that one session of resistance exercise activates rather p70S6k in human muscle via an Akt-independent pathway as reported in the previous studies. KEY WORDS: resistance exercise, mTOR, AMPK, 4E-BP1, p70S6K and Western blotting *[email protected]