Effect of resistance training on mTOR and P70S6K Signaling pathway in skeletal muscle of rats

Document Type : original article



Introduction: Elucidating cell signaling mechanisms involved in muscle hypertrophy is one of the challenges
of sport biologists. Purpose: The mammalian target of Rapamycin (mTOR) is the most important factor in
this process that regulated through phosphorylated the ribosomal protein S6 kinase of 70 kDa (p70S6K) and
increases protein synthesis in skeletal muscle. The purpose of this study was to determine the effect of
resistance training (RT) on total (TmTOR) and phosphorylated (PmTOR) mTOR protein content and total
(TP70) and phosphorylated p70s6k (PhP70) protein content, as markers of hypertrophy regulation in flexor
hallucis longus (FHL) in normal male rats undergoing RT. For this purpose, 12 male Sprague Dawley rats
were randomly divided into control (6 = n) and RT (6 = n). The RT consisted of climbing a ladder carrying a
load suspended from the tail for 8 weeks (5 session week). The load of training was progressively changed 30-
200 % of subject's bodyweight. To investigate muscle samples, 48 hour after the last training session, FHL
muscle was removed while animals were anestheitized. TmTOR, PmTOR, TP70PC and PhP70PC was
measured by ELISA in muscle extract. One-way ANNOVA was used. Results:The results showed RT muscle
had a significantly greater Pour and p70s6k (P=0.001) (P=0.04).but no significant difference in TmTOR and
p70s6k (p=0.421) (p=0.94). Totally, these Conclusion: findings, demonstrate that RT causes hypertrophy
with increased phosphorylation of mTOR and p70s6k fitted.


  1. A. Otto and K. Patel. (2010). Signalling and the control of skeletal muscle size, Exp. Cell Res. 316, (18): 3059–3066.
  2. V. G. Coffey and J. A. Hawley. (2007) The molecular bases of training adaptation, Sport. Med. 37(9): 737–763.
  3. O. A. J. Adegoke, A. Abdullahi, and P. Tavajohi-Fini. (2012). mTORC1 and the regulation of skeletal muscle anabolism and mass, Appl. Physiol. Nutr. Metab.37(3), 395–406,.
  4. K. Watson and K. Baar. (2014). mTOR and the health benefits of exercise, in Seminars in cell & developmental biology. in press.
  5. S. M. Phillips, K. D. Tipton, A. Aarsland, S. E. Wolf, and R. R. Wolfe. (1997). Mixed muscle protein synthesis and breakdown after resistance exercise in humans, Am. J. Physiol. Metab., 36(1). E99.
  6. M. A. Egerman and D. J. Glass. (2013) Signaling pathways controlling skeletal muscle mass, Crit. Rev. Biochem. Mol. Biol. 49 (1): 59–68.
  7. L. Bar-Peled and D. M. Sabatini, Regulation of mTORC1 by amino acids. (2014). Trends Cell Biol. in press
  8. M. Laplante and D. M. Sabatini, mTOR signaling in growth control and disease. (2012). Cell. 149(2): 274–293.
  9. S. Davies, H. Reddy, M. Caivano, and P. Cohen. (2000). Specificity and mechanism of action of some commonly used protein kinase inhibitors, Biochem. J. 351 (1): 95–105.
  10. M. Laplante and D. M. Sabatini. (2009). mTOR signaling at a glance, J. Cell Sci. 122 (20): 3589–3594.
  11. C. A. Goodman. (2014) The Role of mTORC1 in Regulating Protein Synthesis and Skeletal Muscle Mass in Response to Various Mechanical Stimuli,. in press.
  12. S. Sengupta, T. R. Peterson, and D. M. Sabatini. (2010) Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress,
  13. C. A. Goodman, J. W. Frey, D. M. Mabrey, B. L. Jacobs, H. C. Lincoln, J.-S. You, and T. A. Hornberger. (2011). The role of skeletal muscle mTOR in the regulation of mechanical load-induced growth, J. Physiol., 589(22): 5485–5501.
  14. F. K. Haraguchi, C. Lopes de Brito Magalhães, L. X. Neves, R. Cardoso dos Santos, M. L. Pedrosa, and M. Eustaquio Silva. (2013) Whey Protein Modifies Gene Expression Related to Protein Metabolism Affecting Muscle Weight in Resistance-Exercised Rats, Nutrition,40(2): 310–322.
  15. J. Nemati, M. Norshahi, H. Rajabi, and R. Ghrakhanlo. (2010). The effects of eight weeks of resistance training on fast and slow twitch muscle protein content integrin in Wistar rat,. olympic,1 (61): 35–45.[persion].
  16. A. Sofer, K. Lei, C. M. Johannessen, and L. W. Ellisen. (2005). Regulation of mTOR and cell growth in response to energy stress by REDD1, Mol. Cell. Biol., 25 (14): 5834–5845.
  17. N. Eidy, Z. Antonio, and H. Lancha. (2008). Mechanical stimuli of skeletal muscle : implications on mTOR / p70s6k and protein synthesis, Eur. J. Appl. Physiol., 1(102): 253–263.
  18. T. Reynolds, S. Bodine, and J. J. Lawrence. (2002). Control of Ser 2448 phosphorylation in the mammalian target of rapamycin by insulin and skeletal muscle load., J. Biol Chem, 1(277): 17657–17662.
  19. E. Spangenburg, D. Le Roith, C. Ward, and S. Bodine. (2008). A functional insulin-like growth factor receptor is not necessary for load-induced skeletal muscle hypertrophy, J. Physiol. 1(586): 283–291.
  20. A. Philp, D. Hamilton, and K. Baar. (2011). Signals mediating skeletal muscle remodeling by resistance exercise: PI3-kinase independent activation of mTORC1, J. Appl. Physiol. 1(110): 561–568.
  21. R. Pankov, E. Cukierman, K. Clark, K. Matsumoto, C. Hahn, and B. Poulin.(2003). Speciï‌c beta1 integrin site selectively regulates Akt/protein kinase B signaling via local activation of protein phosphatase 2A, J. Biol Chem. 1(278): 18671–18681.
  22. I. Rybakova, J. Patel, and J. Ervasti. (2000) The dystrophin complex forms a mechan- ically strong link between the sarcolemma and costameric actin, Juornal Cell Biol., 1, (150): 1209–1214.
  23. E. Spangenburg and T. McBride. (2006). Inhibition of stretch-activated channels during eccentric muscle contraction attenuates p70S6K activation, J. Appl. Physiol. 1(100): 129–135.
  24. J. M. Joy, D. M. Gundermann, R. P. Lowery, R. Jäger, S. A. Mccleary, M. Purpura, M. D. Roberts, S. M. C. Wilson, T. A. Hornberger, and J. M. Wilson. (2014) Phosphatidic acid enhances mTOR signaling and resistance exercise induced hypertrophy, Nutrition&Metabolism. 1(277): 1–10.
  25. M.-S. Yoon, Y. Sun, E. Arauz, Y. Jiang, and J. Chen. (2011). Phosphatidic acid activates mammalian target of rapamycin complex 1 (mTORC1) kinase by displacing FK506 binding protein 38 (FKBP38) and exerting an allosteric effect., J. Biol Chem. 1(286): 29568–29574.
  26. J. You, J. Frey, and T. Hornberger. (2012). Mechanical stimulation induces mTOR signaling via an ERK-independent mechanism: implications for a direct activation of mTOR by phosphatidic acid, PLoS One. 1(7): 47258.
  27. R. Pearson, P. Dennis, J. Han, N. Williamson, S. Kozma, R. Wettenhall, and G. Thomas. (1995). The principal target of rapamycin-induced p70s6k inactivation is a novel phosphorylation site within a conserved hydrophobic domain, EMBO J. 1(14): 5279–5287.
  28. C. Mayer, J. Zhao, X. Yuan, and I. Grummt. (2004). mTOR-dependent activation of the transcription factor TIF-IA links rRNA synthesis to nutrient availability, Genes Dev., 18 (4): 423–434.
Volume 8, Issue 1 - Serial Number 1
February 2016
Pages 1149-1156
  • Receive Date: 09 February 2016
  • Revise Date: 11 June 2024
  • Accept Date: 31 December 2020
  • First Publish Date: 31 December 2020
  • Publish Date: 21 April 2015