Skip to main content
Log in

Chronic resistance training decreases MuRF-1 and Atrogin-1 gene expression but does not modify Akt, GSK-3β and p70S6K levels in rats

  • Original Article
  • Published:
European Journal of Applied Physiology Aims and scope Submit manuscript

Abstract

Long-term adaptation to resistance training is probably due to the cumulative molecular effects of each exercise session. Therefore, we studied in female Wistar rats the molecular effects of a chronic resistance training regimen (3 months) leading to skeletal muscle hypertrophy in the plantaris muscle. Our results demonstrated that muscle proteolytic genes MuRF-1 and Atrogin-1 were significantly decreased in the exercised group measured 24 h after the last resistance exercise session (41.64 and 61.19%, respectively; P < 0.05). Nonetheless, when measured at the same time point, 4EBP-1, GSK-3β and eIF2Bε mRNA levels and Akt, GSK-3β and p70S6K protein levels (regulators of translation initiation) were not modified. Such data suggests that if gene transcription constitutes a control point in the protein synthesis pathway this regulation probably occurs in early adaptation periods or during extreme situations leading to skeletal muscle remodeling. However, proteolytic gene expression is modified even after a prolonged resistance training regimen leading to moderate skeletal muscle hypertrophy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Armstrong DD, Esser KA (2005) Wnt/beta-catenin signaling activates growth-control genes during overload-induced skeletal muscle hypertrophy. Am J Physiol Cell Physiol 289:C853–C859

    Article  PubMed  CAS  Google Scholar 

  • Bickel CS, Slade J, Mahoney E, Haddad F, Dudley GA, Adams GR (2005) Time course of molecular responses of human skeletal muscle to acute bouts of resistance exercise. J Appl Physiol 98:482–488

    PubMed  CAS  Google Scholar 

  • Bodine SC, Stitt TN, Gonzalez M, Kline WO, Stover GL, Bauerlein R, Zlotchenko E, Scrimgeour A, Lawrence JC, Glass DJ, Yancopoulos GD (2001) Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo. Nat Cell Biol 3:1014–1019

    Article  PubMed  CAS  Google Scholar 

  • Bolster DR, Kimball SR, Jefferson LS (2003) Translational control mechanisms modulate skeletal muscle gene expression during hypertrophy. Exerc Sport Sci 31:111–116

    Article  Google Scholar 

  • Carvalho CR, Thirone AC, Gontijo JA, Velloso LA, Saad MJ (1997) Effect of captopril losartan, and bradykinin on early steps of insulin action. Diabetes 46:1950–1957

    Article  PubMed  CAS  Google Scholar 

  • Childs TE, Spangenburg EE, Vyas DR, Booth FW (2003) Temporal alterations in protein signaling cascades during recovery from muscle atrophy. Am J Physiol Cell Physiol 285:C391–C398

    PubMed  CAS  Google Scholar 

  • Coffey VG, Hawley JA (2007) The molecular bases of training adaptation. Sports Med 37:737–763

    Article  PubMed  Google Scholar 

  • Coffey VG, Reeder DW, Lancaster GI, Yeo WK, Febbraio MA, Yaspelkis BB 3rd, Hawley JA (2007) Effect of high-frequency resistance exercise on adaptive responses in skeletal muscle. Med Sci Sports Exerc 39:2135–2144

    Article  PubMed  Google Scholar 

  • Duncan R, Hershey JW (1985) Regulation of initiation factors during translational repression caused by serum depletion. Abundance, synthesis, and turnover rates. J Biol Chem 260:5486–5492

    PubMed  CAS  Google Scholar 

  • Duncan ND, Williams DA, Lynch GS (1998) Adaptations in rat skeletal muscle following long-term resistance exercise training. Eur J Appl Physiol 77:372–378

    Article  CAS  Google Scholar 

  • Glynn EL, Lujan HL, Kramer VJ, Drummond MJ, DiCarlo SE, Rasmussen BB (2008) A chronic increase in physical activity inhibits fed-state mTOR/S6K1 signaling and reduces IRS-1 serine phosphorylation in rat skeletal muscle. Appl Physiol Nutr Metab 33:93–101

    Article  PubMed  CAS  Google Scholar 

  • Haddad F, Adams GR (2002) Selected contribution: acute cellular and molecular responses to resistance exercise. J Appl Physiol 93:394–403

    PubMed  CAS  Google Scholar 

  • Hansen AK, Fischer CP, Plomgaard P, Andersen JL, Saltin B, Pedersen BK (2005) Skeletal muscle adaptation: training twice every second day vs. training once daily. J Appl Physiol 98:93–99

    Article  PubMed  Google Scholar 

  • Hubal MJ, Gordish-Dressman H, Thompson PD, Price TB, Hoffman EP, Angelopoulos TJ, Gordon PM, Moyna NM, Pescatello LS, Visich PS, Zoeller RF, Seip RL, Clarkson PM (2005) Variability in muscle size and strength gain after unilateral resistance training. Med Sci Sports Exerc 37:964–972

    Article  PubMed  Google Scholar 

  • Kim PL, Staron RS, Phillips SM (2005) Fasted-state skeletal muscle protein synthesis after resistance exercise is altered with training. J Physiol 568:283–290

    Article  PubMed  CAS  Google Scholar 

  • Klitgaard H (1988) A model for quantitative strength training of hindlimb muscles of the rat. J Appl Physiol 64:1740–1745

    PubMed  CAS  Google Scholar 

  • Kostek MC, Chen YW, Cuthbertson DJ, Shi R, Fedele MJ, Esser KA, Rennie MJ (2007) Gene expression responses over 24 h to lengthening and shortening contractions in human muscle: major changes in CSRP3, MUSTN1, SIX1, and FBXO32. Physiol Genomics 31:42–52

    Article  PubMed  CAS  Google Scholar 

  • Kubica N, Kimball SR, Jefferson LS, Farrell PA (2004) Alterations in the expression of mRNAs and proteins that code for species relevant to eIF2B activity after an acute bout of resistance exercise. J Appl Physiol 96:679–687

    Article  PubMed  CAS  Google Scholar 

  • Larsen AE, Tunstall RJ, Carey KA, Nicholas G, Kambadur R, Crowe TC, Cameron-Smith D (2006) Actions of short-term fasting on human skeletal muscle myogenic and atrogenic gene expression. Ann Nutr Metab 50:476–481

    Article  PubMed  CAS  Google Scholar 

  • Léger B, Cartoni R, Praz M, Lamon S, Dériaz O, Crettenand A, Gobelet C, Rohmer P, Konzelmann M, Luthi F, Russell AP (2006) Akt signalling through GSK-3beta, mTOR and Foxo1 is involved in human skeletal muscle hypertrophy and atrophy. J Physiol 576:923–933

    Article  PubMed  Google Scholar 

  • Legerlotz K, Schjerling P, Langberg H, Brüggemann G-P, Niehoff A (2007) The effect of running, strength, and vibration strength training on the mechanical, morphological, and biochemical properties of the Achilles tendon in rats. J Appl Physiol 102:564–572

    Article  PubMed  CAS  Google Scholar 

  • Louis E, Raue U, Yang Y, Jemiolo B, Trappe S (2007) Time course of proteolytic, cytokine, and myostatin gene expression after acute exercise in human skeletal muscle. J Appl Physiol 103:1744–1751

    Article  PubMed  CAS  Google Scholar 

  • Mahoney DJ, Parise G, Melov S, Safdar A, Tarnopolsky MA (2005) Analysis of global mRNA expression in human skeletal muscle during recovery from endurance exercise. FASEB J 19:1498–1500

    PubMed  CAS  Google Scholar 

  • Marino JS, Tausch BJ, Dearth CL, Manacci MV, McLoughlin TJ, Rakyta SJ, Linsenmayer MP, Pizza FX (2008) Beta2-integrins contribute to skeletal muscle hypertrophy in mice. Am J Physiol 295:C1026–C1036

    Article  CAS  Google Scholar 

  • Mascher H, Tannerstedt J, Brink-Elfegoun T, Ekblom B, Gustafsson T, Blomstrand E (2007) Repeated resistance exercise training induces different changes in mRNA expression of MAFbx and MuRF-1 in human skeletal muscle. Am J Physiol Endocrinol Metab 294:E43–E51

    Article  PubMed  Google Scholar 

  • McElhinny AS, Kakinuma K, Sorimachi H, Labeit S, Gregorio CC (2002) Muscle-specific RING finger-1 interacts with titin to regulate sarcomeric M-line and thick filament structure and may have nuclear functions via its interaction with glucocorticoid modulatory element binding protein-1. J Cell Biol 157:125–136

    Article  PubMed  CAS  Google Scholar 

  • Mrosek M, Labeit D, Witt S, Heerklotz H, Von Castelmur E, Labeit S, Mayans O (2007) Molecular determinants for the recruitment of the ubiquitin-ligase MuRF-1 onto M-line titin. FASEB J 21:1383–1392

    Article  PubMed  CAS  Google Scholar 

  • Nedergaard A, Vissing K, Overgaard K, Kjaer M, Schjerling P (2007) Expression patterns of atrogenic and ubiquitin proteasome component genes with exercise: effect of different loading patterns and repeated exercise bouts. J Appl Physiol 103:1513–1522

    Article  PubMed  CAS  Google Scholar 

  • Norenberg KM, Fitts RH (2004) Contractile responses of the rat gastrocnemius and soleus muscles to isotonic resistance exercise. J Appl Physiol 97:2322–2332

    Article  PubMed  CAS  Google Scholar 

  • Phillips SM, Tipton KD, Ferrando AA, Wolfe RR (1999) Resistance training reduces the acute exercise-induced increase in muscle protein turnover. Am J Physiol 276:E118–E124

    PubMed  CAS  Google Scholar 

  • Rommel C, Bodine SC, Clarke BA, Rossman R, Nunez L, Stitt TN, Yancopoulos GD, Glass DJ (2001) Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 pathways. Nat Cell Biol 3:1009–1013

    Article  PubMed  CAS  Google Scholar 

  • Sellman JE, DeRuisseau KC, Betters JL, Lira VA, Soltow QA, Selsby JT, Criswell DS (2006) In vivo inhibition of nitric oxide synthase impairs upregulation of contractile protein mRNA in overloaded plantaris muscle. J Appl Physiol 100:258–265

    Article  PubMed  CAS  Google Scholar 

  • Spencer JA, Eliazer S, Ilaria RL Jr, Richardson JA, Olson EN (2000) Regulation of microtubule dynamics and myogenic differentiation by MURF, a striated muscle RING-finger protein. J Cell Biol 150:771–784

    Article  PubMed  CAS  Google Scholar 

  • Stevenson EJ, Giresi PG, Koncarevic A, Kandarian SC (2003) Global analysis of gene expression patterns during disuse atrophy in rat skeletal muscle. J Physiol 551:33–48

    Article  PubMed  CAS  Google Scholar 

  • Tamaki T, Uchiyama S, Nakano S (1992) A weight-lifting exercise model for inducing hypertrophy in the hindlimb muscles of rats. Med Sci Sports Exerc 24:881–886

    PubMed  CAS  Google Scholar 

  • Vyas DR, Spangenburg EE, Abraha TW, Childs TE, Booth FW (2002) GSK-3beta negatively regulates skeletal myotube hypertrophy. Am J Physiol Cell Physiol 283:C545–C551

    PubMed  CAS  Google Scholar 

  • Wirth O, Gregory EW, Cutlip RG, Miller GR (2003) Control and quantitation of voluntary weight-lifting performance of rats. J Appl Physiol 95:402–412

    PubMed  Google Scholar 

  • Wong TS, Booth FW (1988) Skeletal muscle enlargement with weight-lifting exercise by rats. J Appl Physiol 65:950–954

    PubMed  CAS  Google Scholar 

  • Yang Y, Creer A, Jemiolo B, Trappe S (2005) Time course of myogenic and metabolic gene expression in response to acute exercise in human skeletal muscle. J Appl Physiol 98:1745–1752

    Article  PubMed  CAS  Google Scholar 

  • Yang Y, Jemiolo B, Trappe S (2006) Proteolytic mRNA expression in response to acute resistance exercise in human single skeletal muscle fibers. J Appl Physiol 101:1442–1450

    Article  PubMed  CAS  Google Scholar 

  • Zanchi NE, Lancha-Jr AH (2008) Mechanical stimuli of skeletal muscle: implications on mTOR/p70S6K and protein synthesis. Eur J Appl Physiol 102:253–263

    Article  PubMed  CAS  Google Scholar 

  • Zanchi NE, Lira FS, Seelaender M, Lancha-Jr AH (2009) Experimental chronic low-frequency resistance training produces skeletal muscle hypertrophy in the absence of muscle damage and metabolic stress markers. J Strength Cond Res (in press)

Download references

Acknowledgments

We gratefully acknowledge the technical assistance of Emilia Ribeiro. This study (Grant no. 08/51090-1) was supported by the Brazilian Funding Agency (FAPESP—Fundação de Amparo à Pesquisa do Estado de São Paulo).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Nelo Eidy Zanchi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zanchi, N.E., de Siqueira Filho, M.A., Lira, F.S. et al. Chronic resistance training decreases MuRF-1 and Atrogin-1 gene expression but does not modify Akt, GSK-3β and p70S6K levels in rats. Eur J Appl Physiol 106, 415–423 (2009). https://doi.org/10.1007/s00421-009-1033-6

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00421-009-1033-6

Keywords

Navigation