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Int J Sports Med 2013; 34(10): 861-867
DOI: 10.1055/s-0032-1331758
Physiology & Biochemistry
© Georg Thieme Verlag KG Stuttgart · New York

NFAT Isoforms Regulate Muscle Fiber Type Transition without Altering CaN during Aerobic Training

I. J. Vechetti-Júnior
1   Morphology, São Paulo State University (UNESP), Botucatu, Brazil
,
A. F. Aguiar
1   Morphology, São Paulo State University (UNESP), Botucatu, Brazil
,
R.W. A. de Souza
1   Morphology, São Paulo State University (UNESP), Botucatu, Brazil
,
F.L. A. Almeida
1   Morphology, São Paulo State University (UNESP), Botucatu, Brazil
,
H. B. de Almeida Dias
1   Morphology, São Paulo State University (UNESP), Botucatu, Brazil
,
M. A. de Aguiar Silva
1   Morphology, São Paulo State University (UNESP), Botucatu, Brazil
,
F. R. Carani
1   Morphology, São Paulo State University (UNESP), Botucatu, Brazil
,
R.L. P. Ferraresso
1   Morphology, São Paulo State University (UNESP), Botucatu, Brazil
,
R. F. Carvalho
1   Morphology, São Paulo State University (UNESP), Botucatu, Brazil
,
M. Dal-Pai-Silva
1   Morphology, São Paulo State University (UNESP), Botucatu, Brazil
› Author Affiliations
Further Information

Publication History



accepted after revision 29 November 2012

Publication Date:
02 April 2013 (online)

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Abstract

The purpose of this study was to determine whether the aerobic training-induced fiber-type transition in different muscles is associated with alterations in NFAT isoforms gene expression. We hypothesized that the aerobic training-induced fiber-type transition would be mediated by NFATc1–c3 isoforms without altering the CaN expression. Male Wistar rats (80 days old) were divided into a trained group (T; n=8) that underwent an 8-wk swimming endurance training program (5 days/week) and a control group (C; n=8). After the experimental period, the animals were sacrificed, and the soleus (SOL) and plantaris (PL) muscles were collected for morphometrical, histochemical and molecular analyses. Aerobic training induced a type I-to-type IIA fiber transition in the SOL muscle and a type IIB-to-type IIA fiber transition in the PL muscle, which were concomitant with a significant (p<0.05) increase in NFATc1–c3 gene expression in both the SOL and PL muscles. In contrast, the expression levels of calcineurin (CaN) and NFATc4 remained unchanged. Therefore, our results showed that fiber type switching induced by aerobic training is mediated by NFATc1–c3 isoforms without altering the CaN expression.

Key words

endurance training - calcineurin - NFAT isoforms - fiber-type - skeletal muscle
 

  • References

  • 1 Aguiar AF, Aguiar DH, Felisberto AD, Carani FR, Milanezi RC, Padovani CR, Dal-Pai-Silva M. Effects of creatine supplementation during resistance training on myosin heavy chain (MHC) expression in rat skeletal muscle fibers. J Strength Cond Res 2010; 24: 88-96
    CrossrefPubMedGoogle Scholar
  • 2 Bar A, Pette D. Three fast myosin heavy chains in adult rat skeletal muscle. FEBS Lett 1988; 235: 153
    CrossrefPubMedGoogle Scholar
  • 3 Bigard X, Sanchez H, Zoll J, Mateo P, Rousseau V, Veksler V, Ventura-Clapier R. Calcineurin co-regulates contractile and metabolic components of slow muscle phenotype. J Biol Chem 2000; 275: 19653-19660
    CrossrefPubMedGoogle Scholar
  • 4 Booth FW, Tseng BS, Fluck M, Carson JA. Molecular and cellular adaptation of muscle in response to physical training. Acta Physiol Scand 1998; 162: 343-350
    CrossrefPubMedGoogle Scholar
  • 5 Calabria E, Ciciliot S, Moretti I, Garcia M, Picard A, Dyar KA, Pallafacchina G, Tothova J, Schiaffino S, Murgia M. NFAT isoforms control activity-dependent muscle fiber type specification. Proc Natl Acad Sci USA 2009; 106: 13335-13340
    CrossrefPubMedGoogle Scholar
  • 6 Campos GE, Luecke TJ, Wendeln HK, Toma K, Hagerman FC, Murray T, Ragg KE, Ratamess NA, Kraemer WJ, Staron RS. Muscular adaptations in response to three different resistance-training regimens: specificity of repetition maximum training zones. Eur J Appl Physiol 2002; 88: 50-60
    CrossrefPubMedGoogle Scholar
  • 7 Chin ER, Olson EN, Richardson JA, Yang Q, Humphries C, Shelton JM, Wu H, Zhu W, Bassel-Duby R, Williams RS. A calcineurin-dependent transcriptional pathway controls skeletal muscle fiber type. Genes Dev 1998; 12: 2499-2509
    CrossrefPubMedGoogle Scholar
  • 8 Crabtree GR. Generic signals and specific outcomes: signaling through Ca2+, calcineurin, and NF-AT. Cell 1999; 96: 611-614
    CrossrefPubMedGoogle Scholar
  • 9 de la Pompa JL, Timmerman LA, Takimoto H, Yoshida H, Elia AJ, Samper E, Potter J, Wakeham A, Marengere L, Langille BL, Crabtree GR, Mak TW. Role of the NF-ATc transcription factor in morphogenesis of cardiac valves and septum. Nature 1998; 392: 182-186
    CrossrefPubMedGoogle Scholar
  • 10 Dolmetsch RE, Lewis RS, Goodnow CC, Healy JI. Differential activation of transcription factors induced by Ca2+ response amplitude and duration. Nature 1997; 386: 855-858
    CrossrefPubMedGoogle Scholar
  • 11 Drenning JA, Lira VA, Soltow QA, Canon CN, Valera LM, Brown DL, Criswell DS. Endothelial nitric oxide synthase is involved in calcium-induced Akt signaling in mouse skeletal muscle. Nitric Oxide 2009; 21: 192-200
    CrossrefPubMedGoogle Scholar
  • 12 Dunn SE, Simard AR, Bassel-Duby R, Williams RS, Michel RN. Nerve activity-dependent modulation of calcineurin signaling in adult fast and slow skeletal muscle fibers. J Biol Chem 2001; 276: 45243-45254
    CrossrefPubMedGoogle Scholar
  • 13 Gobatto CA, de Mello MA, Sibuya CY, de Azevedo JR, dos Santos LA, Kokubun E. Maximal lactate steady state in rats submitted to swimming exercise. Comp Biochem Physiol A Mol Integr Physiol 2001; 130: 21-27
    CrossrefPubMedGoogle Scholar
  • 14 Gondret F, Combes S, Lefaucheur L, Lebret B. Effects of exercise during growth and alternative rearing systems on muscle fibers and collagen properties. Reprod Nutr Dev 2005; 45: 69-86
    CrossrefPubMedGoogle Scholar
  • 15 Goodman LA. Simultaneous confidence intervals for contrasts among multinominal populations. Ann Math Stat 1964; 35: 716-725
    Google Scholar
  • 16 Graef IA, Chen F, Chen L, Kuo A, Crabtree GR. Signals transduced by Ca(2+)/Cn and NFATc3/c4 pattern the developing vasculature. Cell 2001; 105: 863-875
    CrossrefPubMedGoogle Scholar
  • 17 Grondard C, Biondi O, Pariset C, Lopes P, Deforges S, Lécolle S, Gaspera BD, Gallien CL, Chanoine C, Charbonnier F. Exercise-induced modulation of calcineurin activity parallels the time course of myofibre transitions. J Cell Physiol 2008; 214: 126-135
    CrossrefPubMedGoogle Scholar
  • 18 Harriss DJ, Atkinson G. Update – ethical standards in sport and exercise science research. Int J Sports Med 2011; 32: 819-821
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Hoey T, Sun Y-L, Williamson K, Xu X. Isolation of two new members of the NF-AT gene family and functional characterization of the NF-AT proteins. Immunity 1995; 2: 461-472
    CrossrefPubMedGoogle Scholar
  • 20 Horsley V, Friday BB, Matteson S, Kegley KM, Gephart J, Pavlath GK. Regulation of the growth of multinucleated muscle cells by an NFATC2-dependent pathway. J Cell Biol 2001; 153: 329-338
    CrossrefPubMedGoogle Scholar
  • 21 Klee CB, Crouch TH, Krinks MH.. Calcineurin: a calcium- and calmodulin-binding protein of the nervous system. Proc Natl Acad Sci USA 1979; 76: 6270-6273
    CrossrefPubMedGoogle Scholar
  • 22 Lamas L, Aoki MS, Ugrinowitsch C, Campos GE, Regazzini M, Moriscot AS, Tricoli V. Expression of genes releated to muscle plasticity after strength and power training regimens. Scand J Med Sci Sports 2010; 2: 216-225
    PubMedGoogle Scholar
  • 23 Liu Y, Cseresnyes Z, Randall WR, Schneider MF. Activity-dependent nuclear translocation and intranuclear distribution of NFATc in adult skeletal muscle fibers. J Cell Biol 2001; 155: 27-39
    CrossrefPubMedGoogle Scholar
  • 24 Magaudda L, Mauro DD, Trimarchi F, Anastasi G. Effects of physical exercises on skeletal muscle fiber: ultrastructural and molecular aspects. Basic Appl Myol 2004; 14: 17-21
    PubMedGoogle Scholar
  • 25 McConell GK, Wadley GD. Potential role of nitric oxide in contraction-stimulated glucose uptake and mitochondrial biogenesis in skeletal muscle. Clin Exp Pharmacol Physiol 2008; 35: 1488-1492
    PubMedGoogle Scholar
  • 26 McCullagh KJ, Calabria E, Pallafacchina G, Ciciliot S, Serrano AL, Argentini C, Kalhovde JM, Lømo T, Schiaffino S. NFATis a nerve activity sensor in skeletal muscle and controls activity-dependent myosin switching. Proc Natl Acad Sci USA 2004; 101: 10590-10595
    CrossrefPubMedGoogle Scholar
  • 27 Michel RN, Dunn SE, Chin ER. Calcineurin and skeletal muscle growth. Proc Nutr Soc 2004; 63: 341-349
    CrossrefPubMedGoogle Scholar
  • 28 Olson EN, Williams RS. Remodeling muscles with calcineurin. Bioessays 2000; 22: 510-519
    CrossrefPubMedGoogle Scholar
  • 29 Pette D, Staron RS. Myosin isoforms, muscle fiber types, and transitions. Microsc Res Tech 2000; 50: 500-509
    CrossrefPubMedGoogle Scholar
  • 30 Pette D, Staron RS. Transitions of muscle fiber phenotypic profiles. Histochem Cell Biol 2001; 115: 359-372
    CrossrefPubMedGoogle Scholar
  • 31 Rao A, Luo C, Hogan PG. Transcription factors of the NFAT family: regulation and function. Annu Rev Immunol 1997; 15: 707-747
    CrossrefPubMedGoogle Scholar
  • 32 Scott W, Stevens J, Binder-Macleod SA. Human skeletal muscle fiber type classifications. Phys Ther 2001; 81: 1810-1816
    PubMedGoogle Scholar
  • 33 Staron RS, Kraemer WJ, Hikida RS, Fry AC, Murray JD, Campos GE. Fiber type composition of four hindlimb muscles of adult Fisher 344 rats. Histochem Cell Biol. 1999; 111: 117-123
    PubMedGoogle Scholar
  • 34 Talmadge RJ, Otis JS, Rittler MR, Garcia ND, Spencer SR, Lees SJ, Naya FJ. Calcineurin activation influences muscle phenotype in a muscle-specific fashion. BMC Cell Biol 2004; 5: 28
    CrossrefPubMedGoogle Scholar
  • 35 Tothova J, Blaauw B, Pallafacchina G, Rudolf R, Argentini C, Reggiani C, Schiaffino S. NFATc1 nucleocytoplasmic shuttling is controlled by nerve activity in skeletal muscle. J Cell Sci 2006; 119: 1604-1611
    CrossrefPubMedGoogle Scholar
  • 36 Trappe S, Harber M, Creer A, Gallagher P, Slivka D, Minchev K, Whitsett D. Single muscle fiber adaptations with marathon training. J Appl Physiol 2006; 101: 721-727
    CrossrefPubMedGoogle Scholar
  • 37 Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 2002; 3 research 0034
    PubMedGoogle Scholar
  • 38 Zar JH. Biostatistical Analysis. 4th ed. Prentice-Hall; New Jersey: 1999: 633
    Google Scholar