Int J Sports Med 2012; 33(10): 846-853
DOI: 10.1055/s-0032-1311585
Genetics & Molecular Biology
© Georg Thieme Verlag KG Stuttgart · New York

Effects of Overtraining on Skeletal Muscle Growth and Gene Expression

W. Xiao
1   Department of Sports Medicine, Shanghai University of Sport, Shanghai, China
,
P. Chen
1   Department of Sports Medicine, Shanghai University of Sport, Shanghai, China
,
J. Dong
1   Department of Sports Medicine, Shanghai University of Sport, Shanghai, China
› Author Affiliations
Further Information

Publication History



accepted after revision 27 February 2012

Publication Date:
16 May 2012 (online)

Abstract

The aim of this study was to investigate the effects of overtraining on skeletal muscle growth and growth-related gene expression. The rats of overtraining group (OT) and overtraining recovery group (OTR) were subject to 11 experimental weeks of overtraining protocol. It was found that the absolute gastrocnemius muscle wet weight of the OT group was significantly lower than that of the sedentary group (23.6%, P<0.01). Serum creatine kinase was significantly higher in the OT and OTR groups than the sedentary group. CD68, CD163, MyoD, myogenin, IL-1β, TNF-α, IGF-I and MGF mRNA did not change in the OT group as compared with the sedentary group. IL-6 and TGF-β1 mRNA in the OT group increased significantly as compared with the sedentary group (2.17 fold and 1.78 fold, respectively; P<0.01). IL-10 mRNA decreased significantly in the OT group (63%, P<0.01) and the OTR group (77%, P<0.01) compared to the sedentary group. COX-2 mRNA decreased significantly in the OT group (60%, P<0.01) and the OTR group (69%, P<0.01) from the sedentary group. uPA mRNA in the OT group was significantly lower than that in the sedentary group (32%, P<0.01). These data suggest that inflammatory cytokines, COX-2 and uPA may play roles in the inhibition of skeletal muscle growth induced by overtraining.

 
  • References

  • 1 Adams GR. Role of insulin-like growth factor-I in the regulation of skeletal muscle adaptation to increased loading. Exerc Sport Sci Rev 1998; 26: 31-60
  • 2 Akdis CA, Blaser K. Mechanisms of interleukin-10-mediated immune suppression. Immunology 2001; 103: 131-136
  • 3 Allbrook D. Skeletal muscle regeneration. Muscle Nerve 1981; 4: 234-245
  • 4 Arnold L, Henry A, Poron F, Baba-Amer Y, van Rooijen N, Plonquet A, Gherardi RK, Chazaud B. Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis. J Exp Med 2007; 204: 1057-1069
  • 5 Bark TH, McNurlan MA, Lang CH, Garlick PJ. Increased protein synthesis after acute IGF-I or insulin infusion is localized to muscle in mice. Am J Physiol 1998; 275: E118-E123
  • 6 Bonavaud S, Charriere-Bertrand C, Rey C, Leibovitch MP, Pedersen N, Frisdal E, Planus E, Blasi F, Gherardi R, Barlovatz-Meimon G. Evidence of a non-conventional role for the urokinase tripartite complex (uPAR/uPA/PAI-1) in myogenic cell fusion. J Cell Sci 1997; 110: 1083-1089
  • 7 Bondesen BA, Mills ST, Kegley KM, Pavlath GK. The COX-2 pathway is essential during early stages of skeletal muscle regeneration. Am J Physiol 2004; 287: C475-C483
  • 8 Carlson ME, Conboy MJ, Hsu M, Barchas L, Jeong J, Agrawal A, Mikels AJ, Agrawal S, Schaffer DV, Conboy IM. Relative roles of TGF-β1 and Wnt in the systemic regulation and aging of satellite cell responses. Aging Cell 2009; 8: 676-689
  • 9 Charge SB, Rudnicki MA. Cellular and molecular regulation of muscle regeneration. Physiol Rev 2004; 84: 209-238
  • 10 Chirgwin JM, Przybyla AE, McDonald RJ, Rutter WJ. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry 1979; 18: 5294-5299
  • 11 Cooney RN, Maish III GO, Gilpin T, Shumate ML, Lang CH, Vary TC. Mechanism of IL-1 induced inhibition of protein synthesis in skeletal muscle. Shock 1999; 11: 235-241
  • 12 Cornelison DD, Wold BJ. Single-cell analysis of regulatory gene expression in quiescent and activated mouse skeletal muscle satellite cells. Dev Biol 1997; 191: 270-283
  • 13 De la Vega E, Hall MR, Wilson KJ, Reverter A, Woods RG, Degnan BM. Stress-induced gene expression profiling in the black tiger shrimp Penaeus monodon. Physiol Genomics 2007; 31: 126-138
  • 14 Dong J, Chen P, Wang R, Yu D, Zhang Y, Xiao W. NADPH oxidase: a target for the modulation of the excessive oxidase damage induced by overtraining in rat neutrophils. Int J Biol Sci 2011; 7: 881-891
  • 15 Durbeej M, Sawatzki SM, Barresi R, Schmainda KM, Allamand V, Michele DE, Campbell KP. Gene transfer establishes primacy of striated vs. smooth muscle sarcoglycan complex in limb-girdle muscular dystrophy. Proc Natl Acad Sci USA 2003; 100: 8910-8915
  • 16 Fibbi G, Barletta E, Dini G, Del Rosso A, Pucci M, Cerletti M, Del Rosso M. Cell invasion is affected by differential expression of the urokinase plasminogen activator/urokinase plasminogen activator receptor system in muscle satellite cells from normal and dystrophic patients. Lab Invest 2001; 81: 27-39
  • 17 Fry AC, Schilling BK, Weiss LW, Chiu LZ. Beta2-Adrenergic receptor downregulation and performance decrements during high-intensity resistance exercise overtraining. J Appl Physiol 2006; 101: 1664-1672
  • 18 Goldspink G. Gene expression in skeletal muscle. Biochem Soc Trans 2002; 30: 285-290
  • 19 Gordon S. Alternative activation of macrophages. Nat Rev Immunol 2003; 3: 23-35
  • 20 Haddad F, Zaldivar F, Cooper DM, Adams GR. IL-6-induced skeletal muscle atrophy. J Appl Physiol 2005; 98: 911-917
  • 21 Harriss DJ, Atkinson G. Update – ethical standards in sport and exercise science research. Int J Sports Med 2011; 32: 819-821
  • 22 Hawke J, Garry D. Myogenic satellite cells: physiology to molecular biology. J Appl Physiol 2001; 91: 534-551
  • 23 Hill M, Goldspink G. Expression and splicing of the insulin-like growth factor gene in rodent muscle is associated with muscle satellite (stem) cell activation following local tissue damage. J Physiol 2003; 549: 409-418
  • 24 Hohl R, Ferraresso RL, De Oliveira RB, Lucco R, Brenzikofer R, De Macedo DV. Development and characterization of an overtraining animal model. Med Sci Sports Exerc 2009; 41: 1155-1163
  • 25 Hurley BF, Redmond RA, Pratley RE, Treuth MS, Rogers MA, Goldberg AP. Effects of strength training on muscle hypertrophy and muscle cell disruption in older men. Int J Sports Med 1995; 16: 378-384
  • 26 Kawanishi N, Yano H, Yokogawa Y, Suzuki K. Exercise training inhibits inflammation in adipose tissue via both suppression of macrophage infiltration and acceleration of phenotypic switching from M1 to M2 macrophages in high-fat-diet induced obese mice. Exerc Immunol Rev 2010; 16: 105-118
  • 27 Koh TJ, Bryer SC, Pucci AM, Sisson TH. Mice deficient in plasminogen activator inhibitor-1 have improved skeletal muscle regeneration. Am J Physiol 2005; 289: C217-C223
  • 28 Koishi K, Zhang M, McLennan I, Harris A. MyoD protein accumulates in satellite cells and is neurally regulated in regenerating myotubes and skeletal muscle fibers. Dev Dyn 1995; 202: 244-254
  • 29 Kuschel R, Deininger M, Meyermann R, Bornemann A, Yablonka-Reuveni Z, Schluesener H. Allograft inflammatory factor-1 is expressed by macrophages in injured skeletal muscle and abrogates proliferation and differentiation of satellite cells. J Neuropathol Exp Neurol 2000; 59: 323-332
  • 30 Lambert JM, Lopez EF, Lindsey ML. Macrophage roles following myocardial infarction. Int J Cardiol 2008; 130: 147-158
  • 31 Langen RC, Schols AM, Kelders MC, Wouters EF, Janssen-Heininger YM. Inflammatory cytokines inhibit myogenic differentiation through activation of nuclear factor-kappaB. FASEB J 2001; 15: 1169-1180
  • 32 Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2 − ΔΔct method. Methods 2001; 25: 402-408
  • 33 Li Y, Foster W, Deasy BM, Chan Y, Prisk V, Tang Y, Cummins J, Huard J. Transforming growth factor-β1 induces the differentiation of myogenic cells into fibrotic cells in injured skeletal muscle: a key event in muscle fibrogenesis. Am J Pathol 2004; 164: 1007-1019
  • 34 Lluis F, Roma J, Suelves M, Parra M, Aniorte G, Gallardo E, Illa I, Rodriguez L, Hughes SM, Carmeliet P, Roig M, Munoz-Canoves P. Urokinase-dependent plasminogen activation is required for efficient skeletal muscle regeneration in vivo. Blood 2001; 97: 1703-1711
  • 35 Mair J, Mayr M, Müller E, Koller A, Haid C, Artner-Dworzak E, Calzolari C, Larue C, Puschendorf B. Rapid adaptation to eccentric exercise-induced muscle damage. Int J Sports Med 1995; 16: 352-356
  • 36 McClung JM, Davis JM, Carson JA. Ovarian hormone status and skeletal muscle inflammation during recovery from disuse in rats. Exp Physiol 2007; 92: 219-232
  • 37 McKenzie DC. Markers of Excessive Exercise. Can J Appl Physiol 1999; 24: 66-73
  • 38 McLennan I. Degenerating and regenerating skeletal muscle contain several populations of macrophages with distinct spatial and temporal distributions. J Anat 1996; 188: 17-28
  • 39 McLoon L, Nguyen L, Wirtschafter J. Time course of the regenerative responses in bupivacaine injured orbicularis oculi muscle. Cell Tissue Res 1998; 294: 439-447
  • 40 Mendias CL, Tatsumi R, Allen RE. Role of cyclooxygenase-1 and -2 in satellite cell proliferation, differentiation, and fusion. Muscle Nerve 2004; 30: 497-500
  • 41 Milne CJ. Rhabdomyolysis, myoglobinuria and exercise. Sports Med 1988; 6: 93-106
  • 42 Mirza R, DiPietro LA, Koh TJ. Selective and specific macrophage ablation is detrimental to wound healing in mice. Am J Pathol 2009; 175: 2454-2462
  • 43 Moldawer LL, Rogy MA, Lowry SF. The role of cytokines in cancer cachexia. JPEN J Parenter Enteral Nutr 1992; 16: 43S-49S
  • 44 Munoz-Canoves P, Miralles F, Baiget M, Felez J. Inhibition of urokinase-type plasminogen activator (uPA) abrogates myogenesis in vitro. Thromb Haemost 1997; 77: 526-534
  • 45 Nathan CF. Secretory products of macrophages. J Clin Invest 1987; 79: 319-326
  • 46 Nikolaidis MG, Papazisis KT, Kortsaris AH, Mougios V. Exercise-induced changes in c-Fos protein levels in skeletal muscle of trained and untrained rats. Int J Sports Med 2003; 24: 96-100
  • 47 Novak ML, Billich W, Smith SM, Sukhija KB, McLoughlin TJ, Hornberger TA, Koh TJ. COX-2 inhibitor reduces skeletal muscle hypertrophy in mice. Am J Physiol 2009; 296: R1132-R1139
  • 48 Novak ML, Bryer SC, Cheng M, Nguyen MH, Conley KL, Cunningham AK, Xue B, Sisson TH, You JS, Hornberger TA, Koh TJ. Macrophage-specific expression of urokinase-type plasminogen activator promotes skeletal muscle regeneration. J Immunol 2011; 187: 1448-1457
  • 49 Peake J, Della Gatta P, Cameron-Smith D. Aging and its effects on inflammation in skeletal muscle at rest and following exercise-induced muscle injury. Am J Physiol 2010; 298: R1485-R1495
  • 50 Pestka S, Krause CD, Sarkar D, Walter MR, Shi Y, Fisher PB. Interleukin-10 and related cytokines and receptors. Annu Rev Immunol 2004; 22: 929-979
  • 51 Ricardo SD, van Goor H, Eddy AA. Macrophage diversity in renal injury and repair. J Clin Invest 2008; 118: 3522-3530
  • 52 Schmalbruch H, Hellhammer U. The number of nuclei in adult rat muscles with special reference to satellite cells. Anat Rec 1977; 189: 169-175
  • 53 Seale P, Rudnicki M. A new look at the origin, function, and “stem-cell” status of muscle satellite cells. Dev Biol 2000; 218: 115-124
  • 54 Sinert R, Kohl L, Rainone T, Scalea T. Exercise-induced rhabdomyolysis. Ann Emerg Med 1994; 23: 1301-1306
  • 55 Sisson TH, Nguyen MH, Yu B, Novak ML, Simon RH, Koh TJ. Urokinase-type plasminogen activator increases hepatocyte growth factor activity required for skeletal muscle regeneration. Blood 2009; 114: 5052-5061
  • 56 Spiegelman BM, Hotamisligil GS. Through thick and thin: wasting, obesity, and TNF alpha. Cell 1993; 73: 627
  • 57 Stadelmann WK, Digenis AG, Tobin GR. Physiology and healing dynamics of chronic cutaneous wounds. Am J Surg 1998; 176: 26S-38S
  • 58 Steed DL. The role of growth factors in wound healing. Surg Clin North Am 1997; 77: 575-586
  • 59 Tamaki T, Uchiyama S, Uchiyama Y, Akatsuka A, Yoshimura S, Roy R, Edgerton V. Limited myogenic response to a single bout of weight-lifting exercise in old rats. Am J Physiol 2000; 278: C1143-C1152
  • 60 Thomas AP, Dunn TN, Oort PJ, Grino M, Adams SH. Inflammatory phenotyping identifies cd11d as a gene markedly induced in white adipose tissue in obese rodents and women. J Nutr 2011; 141: 1172-1180
  • 61 Tidball JG, Villalta SA. Regulatory interactions between muscle and the immune system during muscle regeneration. Am J Physiol 2010; 298: R1173-R1187
  • 62 Trappe TA, White F, Lambert CP, Cesar D, Hellerstein M, Evans WJ. Effect of ibuprofen and acetaminophen on postexercise muscle protein synthesis. Am J Physiol 2002; 282: E551-E556
  • 63 Tsujinaka T, Ebisui C, Fujita J, Kishibuchi M, Morimoto T, Ogawa A, Katsume A, Ohsugi Y, Kominami E, Monden M. Muscle undergoes atrophy in association with increase of lysosomal cathepsin activity in interleukin-6 transgenic mouse. Biochem Biophys Res Commun 1995; 207: 168-174
  • 64 Wang R, Chen P. Modulation of NKT cells and Th1/Th2 imbalance after α-GalCer treatment in progressive load-trained rats. Int J Biol Sci 2009; 5: 338-343
  • 65 Yablonka-Reuveni Z, Rivera AJ. Temporal expression of regulatory and structural muscle proteins during myogenesis of satellite cells on isolated adult rat fibers. Dev Biol 1994; 164: 588-603
  • 66 Yamin C, Amir O, Sagiv M, Attias E, Meckel Y, Eynon N, Sagiv M, Amir RE. ACE ID genotype affects blood creatine kinase response to eccentric exercise. J Appl Physiol 2007; 103: 2057-2061
  • 67 Yang SY, Goldspink G. Different roles of the IGF-I Ec peptide (MGF) and mature IGF-I in myoblast proliferation and differentiation. FEBS Lett 2002; 522: 156-160
  • 68 Zheng J, Wang R, Zambraski E, Wu D, Jacobson KA, Liang BT. Protective roles of adenosine A1, A2A, and A3 receptors in skeletal muscle ischemia and reperfusion injury. Am J Physiol 2007; 293: H3685-H3691