Skip to main content

Advertisement

SpringerLink
Log in

Calcineurin A and CaMKIV transactivate PGC-1α promoter, but differentially regulate cytochrome c promoter in rat skeletal muscle

  • Skeletal Muscle
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

In skeletal muscle, slow-twitch fibers are highly dependent on mitochondrial oxidative metabolism suggesting the existence of common regulatory pathways in the control of slow muscle-specific protein expression and mitochondrial biogenesis. In this study, we determined whether peroxisome proliferator-activated receptor γ co-activator-1α (PGC-1α) could transactivate promoters of nuclear-encoded mitochondrial protein (cytochrome c) and muscle-specific proteins (fast troponin I, MyoD). We also investigated if calcineurin A (CnA) and calcium/calmodulin kinase IV (CaMKIV) were involved in the regulation of PGC-1α and cytochrome c promoter. For this purpose, we took advantage of the gene electrotransfer technique, which allows acute expression of a gene of interest. Electrotransfer of a PGC-1α expression vector into rat Tibialis anterior muscle induced a strong transactivation of cytochrome c promoter (P < 0.001) independent of nuclear respiratory factor 1. PGC-1α gene electrotransfer did not transactivate fast troponin I promoter, whereas it did transactivate MyoD promoter (P < 0.05). Finally, whereas electrotransfers of CnA or CaMKIV expression vectors transactivated PGC-1α promoter (P < 0.001), gene electrotransfer of CaMKIV was only able to transactivate cytochrome c promoter. Taken together, these data suggest that CnA triggers PGC-1α promoter transactivation to drive the expression of non-mitochondrial proteins.

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

Access this article

Log in via an institution

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
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Akimoto T, Ribar TJ, Williams RS, Yan Z (2004) Skeletal muscle adaptation in response to voluntary running in Ca2+/calmodulin-dependent protein kinase IV-deficient mice. Am J Physiol Cell Physiol 287:C1311–C1319

    Article  PubMed  CAS  Google Scholar 

  2. Alway SE, Degens H, Krishnamurthy G, Smith CA (2002) Potential role for Id myogenic repressors in apoptosis and attenuation of hypertrophy in muscles of aged rats. Am J Physiol Cell Physiol 283:C66–C76

    PubMed  CAS  Google Scholar 

  3. Andersson U, Scarpulla RC (2001) Pgc-1-related coactivator, a novel, serum-inducible coactivator of nuclear respiratory factor 1-dependent transcription in mammalian cells. Mol Cell Biol 21:3738–3749

    Article  PubMed  CAS  Google Scholar 

  4. Bigard X, Sanchez H, Zoll J, Mateo P, Rousseau V, Veksler V, Ventura-Clapier R (2000) Calcineurin co-regulates contractile and metabolic components of slow muscle phenotype. J Biol Chem 275:19653–19660

    Article  PubMed  CAS  Google Scholar 

  5. Calvo S, Stauffer J, Nakayama M, Buonanno A (1996) Transcriptional control of muscle plasticity: differential regulation of troponin I genes by electrical activity. Dev Genet 19:169–181

    Article  PubMed  CAS  Google Scholar 

  6. Chang JH, Lin KH, Shih CH, Chang YJ, Chi HC, Chen SL (2006) Myogenic basic helix-loop-helix proteins regulate the expression of peroxisomal proliferator activated receptor-gamma coactivator-1alpha. Endocrinology 147:3093–3106

    Article  PubMed  CAS  Google Scholar 

  7. Chin ER, Olson EN, Richardson JA, Yang Q, Humphries C, Shelton JM, Wu H, Zhu W, Bassel-Duby R, Williams RS (1998) A calcineurin-dependent transcriptional pathway controls skeletal muscle fiber type. Genes Dev 12:2499–2509

    PubMed  CAS  Google Scholar 

  8. Daitoku H, Yamagata K, Matsuzaki H, Hatta M, Fukamizu A (2003) Regulation of PGC-1 promoter activity by protein kinase B and the forkhead transcription factor FKHR. Diabetes 52:642–649

    Article  PubMed  CAS  Google Scholar 

  9. Durieux AC, Bonnefoy R, Busso T, Freyssenet D (2004) In vivo gene electrotransfer into skeletal muscle: effects of plasmid DNA on the occurrence and extent of muscle damage. J Gene Med 6:809–816

    Article  PubMed  CAS  Google Scholar 

  10. Durieux AC, Bonnefoy R, Manissolle C, Freyssenet D (2002) High-efficiency gene electrotransfer into skeletal muscle: description and physiological applicability of a new pulse generator. Biochem Biophys Res Commun 296:443–450

    Article  PubMed  CAS  Google Scholar 

  11. Evans MJ, Scarpulla RC (1988) Both upstream and intron sequence elements are required for elevated expression of the rat somatic cytochrome c gene in COS-1 cells. Mol Cell Biol 8:35–41

    PubMed  CAS  Google Scholar 

  12. Evans MJ, Scarpulla RC (1989) Interaction of nuclear factors with multiple sites in the somatic cytochrome c promoter. Characterization of upstream NRF-1, ATF, and intron Sp1 recognition sequences. J Biol Chem 264:14361–14368

    PubMed  CAS  Google Scholar 

  13. Falkenberg M, Gaspari M, Rantanen A, Trifunovic A, Larsson NG, Gustafsson CM (2002) Mitochondrial transcription factors B1 and B2 activate transcription of human mtDNA. Nat Genet 31:289–294

    Article  PubMed  CAS  Google Scholar 

  14. Fisher RP, Clayton DA (1985) A transcription factor required for promoter recognition by human mitochondrial RNA polymerase. Accurate initiation at the heavy- and light-strand promoters dissected and reconstituted in vitro. J Biol Chem 260:11330–11338

    PubMed  CAS  Google Scholar 

  15. Fisher RP, Clayton DA (1988) Purification and characterization of human mitochondrial transcription factor 1. Mol Cell Biol 8:3496–3509

    PubMed  CAS  Google Scholar 

  16. Freyssenet D, Di Carlo M, Hood DA (1999) Calcium-dependent regulation of cytochrome c gene expression in skeletal muscle cells. Identification of a protein kinase c-dependent pathway. J Biol Chem 274:9305–9311

    Article  PubMed  CAS  Google Scholar 

  17. Freyssenet D, Irrcher I, Connor MK, Di Carlo M, Hood DA (2004) Calcium-regulated changes in mitochondrial phenotype in skeletal muscle cells. Am J Physiol Cell Physiol 286:C1053–C1061

    Article  PubMed  CAS  Google Scholar 

  18. Garcia-Roves PM, Huss J, Holloszy JO (2006) Role of calcineurin in exercise-induced mitochondrial biogenesis. Am J Physiol Endocrinol Metab 290:E1172–E1179

    Article  PubMed  CAS  Google Scholar 

  19. Gopalakrishnan L, Scarpulla RC (1994) Differential regulation of respiratory chain subunits by a CREB-dependent signal transduction pathway. Role of cyclic AMP in cytochrome c and COXIV gene expression. J Biol Chem 269:105–113

    PubMed  CAS  Google Scholar 

  20. Gugneja S, Virbasius CM, Scarpulla RC (1996) Nuclear respiratory factors 1 and 2 utilize similar glutamine-containing clusters of hydrophobic residues to activate transcription. Mol Cell Biol 16:5708–5716

    PubMed  CAS  Google Scholar 

  21. Handschin C, Rhee J, Lin J, Tarr PT, Spiegelman BM (2003) An autoregulatory loop controls peroxisome proliferator-activated receptor gamma coactivator 1alpha expression in muscle. Proc Natl Acad Sci USA 100:7111–7116

    Article  PubMed  CAS  Google Scholar 

  22. Herzig RP, Scacco S, Scarpulla RC (2000) Sequential serum-dependent activation of CREB and NRF-1 leads to enhanced mitochondrial respiration through the induction of cytochrome c. J Biol Chem 275:13134–13141

    Article  PubMed  CAS  Google Scholar 

  23. Herzog B, Cardenas J, Hall RK, Villena JA, Budge PJ, Giguere V, Granner DK, Kralli A (2006) Estrogen-related receptor alpha is a repressor of phosphoenolpyruvate carboxykinase gene transcription. J Biol Chem 281:99–106

    Article  PubMed  CAS  Google Scholar 

  24. Hunter JG, van Delft MF, Rachubinski RA, Capone JP (2001) Peroxisome proliferator-activated receptor gamma ligands differentially modulate muscle cell differentiation and MyoD gene expression via peroxisome proliferator-activated receptor gamma-dependent and -independent pathways. J Biol Chem 276:38297–38306

    PubMed  CAS  Google Scholar 

  25. Huss JM, Kopp RP, Kelly DP (2002) Peroxisome proliferator-activated receptor coactivator-1alpha (PGC-1alpha) coactivates the cardiac-enriched nuclear receptors estrogen-related receptor-alpha and -gamma. Identification of novel leucine-rich interaction motif within PGC-1alpha. J Biol Chem 277:40265–40274

    Article  PubMed  CAS  Google Scholar 

  26. Huss JM, Torra IP, Staels B, Giguere V, Kelly DP (2004) Estrogen-related receptor alpha directs peroxisome proliferator-activated receptor alpha signaling in the transcriptional control of energy metabolism in cardiac and skeletal muscle. Mol Cell Biol 24:9079–9091

    Article  PubMed  CAS  Google Scholar 

  27. Johnson SE, Wang X, Hardy S, Taparowsky EJ, Konieczny SF (1996) Casein kinase II increases the transcriptional activities of MRF4 and MyoD independently of their direct phosphorylation. Mol Cell Biol 16:1604–1613

    PubMed  CAS  Google Scholar 

  28. Kelly DP, Scarpulla RC (2004) Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. Genes Dev 18:357–368

    Article  PubMed  CAS  Google Scholar 

  29. Kraus B, Pette D (1997) Quantification of MyoD, myogenin, MRF4 and Id-1 by reverse-transcriptase polymerase chain reaction in rat muscles—effects of hypothyroidism and chronic low-frequency stimulation. Eur J Biochem 247:98–106

    Article  PubMed  CAS  Google Scholar 

  30. Kubis HP, Haller EA, Wetzel P, Gros G (1997) Adult fast myosin pattern and Ca2+-induced slow myosin pattern in primary skeletal muscle culture. Proc Natl Acad Sci USA 94:4205–4210

    Article  PubMed  CAS  Google Scholar 

  31. Lin J, Wu H, Tarr PT, Zhang CY, Wu Z, Boss O, Michael LF, Puigserver P, Isotani E, Olson EN, Lowell BB, Bassel-Duby R, Spiegelman BM (2002) Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres. Nature 418:797–801

    Article  PubMed  CAS  Google Scholar 

  32. Meier JL, Stinski MF (1996) Regulation of human cytomegalovirus immediate-early gene expression. Intervirology 39:331–342

    PubMed  CAS  Google Scholar 

  33. Meissner JD, Gros G, Scheibe RJ, Scholz M, Kubis HP (2001) Calcineurin regulates slow myosin, but not fast myosin or metabolic enzymes, during fast-to-slow transformation in rabbit skeletal muscle cell culture. J Physiol 533:215–226

    Article  PubMed  CAS  Google Scholar 

  34. Mootha VK, Handschin C, Arlow D, Xie X, St Pierre J, Sihag S, Yang W, Altshuler D, Puigserver P, Patterson N, Willy PJ, Schulman IG, Heyman RA, Lander ES, Spiegelman BM (2004) Erralpha and Gabpa/b specify PGC-1alpha-dependent oxidative phosphorylation gene expression that is altered in diabetic muscle. Proc Natl Acad Sci USA 101:6570–6575

    Article  PubMed  CAS  Google Scholar 

  35. Nakayama M, Stauffer J, Cheng J, Banerjee-Basu S, Wawrousek E, Buonanno A (1996) Common core sequences are found in skeletal muscle slow- and fast-fiber-type-specific regulatory elements. Mol Cell Biol 16:2408–2417

    PubMed  CAS  Google Scholar 

  36. Ojuka EO, Jones TE, Han DH, Chen M, Holloszy JO (2003) Raising Ca2+ in L6 myotubes mimics effects of exercise on mitochondrial biogenesis in muscle. FASEB J 17:675–681

    Article  PubMed  CAS  Google Scholar 

  37. Ojuka EO, Jones TE, Han DH, Chen M, Wamhoff BR, Sturek M, Holloszy JO (2002) Intermittent increases in cytosolic Ca2+ stimulate mitochondrial biogenesis in muscle cells. Am J Physiol Endocrinol Metab 283:E1040–E1045

    PubMed  CAS  Google Scholar 

  38. Passier R, Zeng H, Frey N, Naya FJ, Nicol RL, McKinsey TA, Overbeek P, Richardson JA, Grant SR, Olson EN (2000) CaM kinase signaling induces cardiac hypertrophy and activates the MEF2 transcription factor in vivo. J Clin Invest 105:1395–1406

    Article  PubMed  CAS  Google Scholar 

  39. Rose AJ, Kiens B, Richter EA (2006) Ca2+–calmodulin-dependent protein kinase expression and signalling in skeletal muscle during exercise. J Physiol 574:889–903

    Article  PubMed  CAS  Google Scholar 

  40. Ryder JW, Bassel-Duby R, Olson EN, Zierath JR (2003) Skeletal muscle reprogramming by activation of calcineurin improves insulin action on metabolic pathways. J Biol Chem 278:44298–44304

    Article  PubMed  CAS  Google Scholar 

  41. Scarpulla RC (2006) Nuclear control of respiratory gene expression in mammalian cells. J Cell Biochem 97:673–683

    Article  PubMed  CAS  Google Scholar 

  42. Schreiber SN, Emter R, Hock MB, Knutti D, Cardenas J, Podvinec M, Oakeley EJ, Kralli A (2004) The estrogen-related receptor alpha (ERRalpha) functions in PPARgamma coactivator 1alpha (PGC-1alpha)-induced mitochondrial biogenesis. Proc Natl Acad Sci USA 101:6472–6477

    Article  PubMed  CAS  Google Scholar 

  43. Schreiber SN, Knutti D, Brogli K, Uhlmann T, Kralli A (2003) The transcriptional coactivator PGC-1 regulates the expression and activity of the orphan nuclear receptor estrogen-related receptor alpha (ERRalpha). J Biol Chem 278:9013–9018

    Article  PubMed  CAS  Google Scholar 

  44. St-Pierre J, Lin J, Krauss S, Tarr PT, Yang R, Newgard CB, Spiegelman BM (2003) Bioenergetic analysis of peroxisome proliferator-activated receptor gamma coactivators 1alpha and 1beta (PGC-1alpha and PGC-1beta) in muscle cells. J Biol Chem 278:26597–26603

    Article  PubMed  CAS  Google Scholar 

  45. Vega RB, Huss JM, Kelly DP (2000) The coactivator PGC-1 cooperates with peroxisome proliferator-activated receptor alpha in transcriptional control of nuclear genes encoding mitochondrial fatty acid oxidation enzymes. Mol Cell Biol 20:1868–1876

    Article  PubMed  CAS  Google Scholar 

  46. Virbasius CA, Virbasius JV, Scarpulla RC (1993) NRF-1, an activator involved in nuclear-mitochondrial interactions, utilizes a new DNA-binding domain conserved in a family of developmental regulators. Genes Dev 7:2431–2445

    PubMed  CAS  Google Scholar 

  47. World Medical Association, American Physiological Society (2002) Guiding principles for research involving animals and human beings. Am J Physiol Regul Integr Comp Physiol 283:R281–R283

    Google Scholar 

  48. Wu H, Kanatous SB, Thurmond FA, Gallardo T, Isotani E, Bassel-Duby R, Williams RS (2002) Regulation of mitochondrial biogenesis in skeletal muscle by CaMK. Science 296:349–352

    Article  PubMed  CAS  Google Scholar 

  49. Wu Z, Huang X, Feng Y, Handschin C, Feng Y, Gullicksen PS, Bare O, Labow M, Spiegelman B, Stevenson SC (2006) Transducer of regulated CREB-binding proteins (TORCs) induce PGC-1alpha transcription and mitochondrial biogenesis in muscle cells. Proc Natl Acad Sci USA 103:14379–14384

    Article  PubMed  CAS  Google Scholar 

  50. Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, Troy A, Cinti S, Lowell B, Scarpulla RC, Spiegelman BM (1999) Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98:115–124

    Article  PubMed  CAS  Google Scholar 

  51. Zong H, Ren JM, Young LH, Pypaert M, Mu J, Birnbaum MJ, Shulman GI (2002) AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. Proc Natl Acad Sci USA 99:15983–15987

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors gratefully acknowledge S. Konieczny (Department of Biological Sciences, Purdue University, IN, USA) for donating the TnI and MyoD promoter reporter plasmids, E. Olson (University of Texas, Dallas, TX, USA) for donating the CnA and CaMKIV expression vectors, R. Scarpulla (Northwestern University Medical School, IL, USA) for donating the cytochrome c promoter reporter plasmids and NRF-1 expression vector and B. Spiegelman (Harvard Medical School, Boston, MA, USA) for donating the PGC-1α expression vector.

Author information

Authors and Affiliations

  1. Unité Physiologie et Physiopathologie de l’Exercice et Handicap EA 3062, Faculté de Médecine, Université Jean Monnet, 15 rue Ambroise Paré, 42023, Saint-Etienne Cedex 2, France

    Ibtissem Guerfali, Chloé Manissolle, Anne-Cécile Durieux, Régis Bonnefoy & Damien Freyssenet

  2. Laboratoire de Biochimie et Interaction Moléculaire, Unité de Recherche 02/UR/09-01, Institut Supérieur de Biotechnologie, Monastir, Tunisia

    Ibtissem Guerfali & Aghleb Bartegi

Authors
  1. Ibtissem Guerfali
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chloé Manissolle
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anne-Cécile Durieux
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Régis Bonnefoy
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Aghleb Bartegi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Damien Freyssenet
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Damien Freyssenet.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Guerfali, I., Manissolle, C., Durieux, AC. et al. Calcineurin A and CaMKIV transactivate PGC-1α promoter, but differentially regulate cytochrome c promoter in rat skeletal muscle. Pflugers Arch - Eur J Physiol 454, 297–305 (2007). https://doi.org/10.1007/s00424-007-0206-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00424-007-0206-6

Keywords

Search

Navigation