Skip to main content
SpringerLink
Log in

Regulation of expression of contractile proteins with cardiac hypertrophy and failure

  • Part III: Norman and Failing Myocardium
  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Transitions in sarcomeric α-actin and cardiac myosin heavy chain (MHC) gene expression have been useful as molecular markers for the development of cardiac hypertrophy and failure. In simpler model systems, α-actin expression has been useful in delineating some of the molecular pathways responsible for its induction following growth stimulation in vitro. In this study, we report that the effects of adrenergic agonists on α-actin expression in neonatal cardiocytes is dependent upon the culture conditions. In cardiocytes plated at 5 x 104 cells/cm2, skeletal α-actin mRNA levels represent 47%, 37% or 42% of total sarcomeric α-actin accumulations following administrations of 4 μM norepinephrine (NE), isoproterenol (Iso), or phenylephrine (PE), respectively. Cultured cardiocytes treated with vehicle (ascorbate) only accumulated 19% skeletal α-actin. Under these tissue culture conditions, in contrast to data reported previously, skeletal α-actin expression is regulated by both α- and β-adrenergic agonist stimulation. Furthermore, we present data showing that an endogenous anti-β-MHC transcript is regulated by both pressure-overload- or thyroxine-induced cardiac hypertrophy. Although anti-β-MHC transcripts do not play a major role in regulating β-MHC gene expression, the presence of this antisense transcript is associated with a novel set of β-MHC degradation products. In vitro studies, where oligonucleotides complementary to β-MHC have been introduced into cardiomyoctyes, show that the mRNA levels of β-MHC are decreased by 14–21 % within 72 h after addition of the oligonucleotides. This result together with the presence of β-MHC degradation products suggest that endogenous anti-β-MHC transcripts may be involved in a post-transcriptional regulatory mechanism affecting the steady-state levels of β-MHC expression.

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

Similar content being viewed by others

References

  1. Carrier L, Boheler KR, Chassagne C, de la Bastie D, Wisnewsky C, Lakatta EG, Schwartz K: Expression of the sarcomeric actin isogenes in the rat heart with development and senescence. Circ Res 70: 999–1005, 1992

    Google Scholar 

  2. Sassoon DA, Garner I, Buckingham M: Transcripts of α-cardiac and α-skeletal actins are markers for myogenesis in the mouse embryo. Development 104: 155–164, 1988

    Google Scholar 

  3. Babai F, Musevi-Aghdam J, Schurch W, Royal A, Gabbiani G: Coexpression of α-sarcomeric actin, α-smooth muscle actin and desmin during myogenesis in rat and mouse embryos. Differentiation 44: 132–142, 1990

    Google Scholar 

  4. Mayer Y, Czosnek H, Zeelon PE, Yaffe D, Nudel U: Expression of the genes coding for the skeletal muscle and cardiac actins in the heart. Nuc Acids Res 12: 1087–1100, 1984

    Google Scholar 

  5. Winegrad S, Wisnewsky C, Schwartz K: Effect of thyroid hormone on the accumulation of mRNA for skeletal and cardiac α-actin in hearts from normal and hypophysectomized rats. Proc Natl Acad Sci USA 87: 2456–2460, 1990

    Google Scholar 

  6. Collie ESR, Muscat GEO: The human skeletal α-actin promoter is regulated by thyroid hormone: identification of a thyroid hormone response element. Cell Growth & Differentiation 3: 31–42, 1992

    Google Scholar 

  7. Schwartz K, de la Bastie D, Bouveret P, Oliviero P, Alonso S, and Buckingham ME: ol-Skeletal actin mRNAs accumulate in hypertrophied adult rat hearts. Circ Res 59: 551–555, 1986

    Google Scholar 

  8. Izumo S, Nadal-Ginard B, Mahdavi V: Protooncogene induction and reprogramming of cardiac gene expression produced by pressure overload. Proc Natl Acad Sci USA 85: 339–343, 1988

    Google Scholar 

  9. Karns LR, Kariya K, Simpson PC: M-CAT, CArG, and Spl elements are required for α1-adrenergic induction of the skeletal α-actin promoter during cardiac myocyte hypertrophy. J Biol Chem 270: 410–417, 1995

    Google Scholar 

  10. Bishopric NH, Kedes L: Adrenergic regulation of the skeletal α-actin gene promoter during myocardial cell hypertrophy. Proc Natl Acad Sci USA 88: 2132–2136, 1991

    Google Scholar 

  11. Bishopric NH, Sato B, Webster KA: β-adrenergic regulation of a myocardial actin gene via a cyclic AMP-independent pathway. J Biol Chem 267: 20932–20936, 1992

    Google Scholar 

  12. Bishopric NH, Simpson PC, Ordahl CP: Induction of the skeletal α-actin gene in α1-adrenoceptor-mediated hypertrophy of rat cardiac myocytes. J Clin Invest 80: 1194–1199, 1987

    Google Scholar 

  13. Mahdavi V, Izumo S, Nadal Ginard B: Developmental and hormonal regulation of sarcomeric myosin heavy chain gene family. Circ Res 60: 804–814, 1987

    Google Scholar 

  14. Ng WA, Grupp IL, Subramaniam A, Robbins J: Cardiac myosin heavy chain mRNA expression and myocardial function in the mouse heart. Circ Res 68: 1742–1750, 1991

    Google Scholar 

  15. Everett AW, Sinha AM, Umeda PK, Jakovcic S, Rabinowitz M, Zak R: Regulation of myosin synthesis by thyroid hormone: relative change in the alpha- and beta-myosin heavy chain mRNA levels in rabbit heart. Biochemistry 23: 1596–1599, 1984

    Google Scholar 

  16. Effron MB, Bhatnagar GM, Spurgeon HA, Ruano Arroyo G, Lakatta EG: Changes in myosin isoenzymes, ATPase activity, and contraction duration in rat cardiac muscle with aging can be modulated by thyroxine. Circ Res 60: 238–245, 1987

    Google Scholar 

  17. Waspe LE, Ordahl CP, Simpson PC: The cardiac β-myosin heavy chain isogene is induced selectively in a1-adrenergic receptor-stimulated hypertrophy of cultured rat heart myocytes. J Clin Invest 85: 1206–1214, 1990

    Google Scholar 

  18. Kariya K, Karns LR, Simpson PC: An enhancer core element mediates stimulation of the rat β-myosin heavy chain promoter by an α1-adrenergic agonist and activated β-protein kinase C in hypertrophy of cardiac myocytes. J Biol Chem 269: 3775–3782, 1994

    Google Scholar 

  19. Kariya K, Farrance IK, and Simpson PC: Transcriptional enhancer factor-1 in cardiac myocytes interacts with an alpha 1-adrenergic- and beta-protein kinase C-inducible element in the rat beta-myosin heavy chain promoter. J Biol Chem 268: 26658–26662, 1993

    Google Scholar 

  20. Swynghedauw B: Developmental and functional adaptation of contractile proteins in cardiac and skeletal muscles. Physiol Rev 66: 710–771, 1986

    Google Scholar 

  21. Izumo S, Lompré A, Matsuoka R, Koren G, Schwartz K, Nadal-Ginard B, Mahdavi V: Myosin heavy chain messenger RNA and protein isoform transitions during cardiac hypertrophy. J Clin Invest 79: 970–977, 1987

    Google Scholar 

  22. Lompre AM, Nadal-Ginard B, and Mabdavi V: Expression of the cardiac ventricular α and β-myosin heavy chain genes is developmentally and hormonally regulated. J Biol Chem 259: 6437–6446, 1984

    Google Scholar 

  23. Nagai R, Pritzi N, Low RB, Stirewalt WS, Zak R, Alpert NR, Litten RZ: Myosin isozyme synthesis and mRNA levels in pressure-overloaded rabbit hearts. Circ Res 60: 692–699, 1987

    Google Scholar 

  24. Morkin E: Regulation of myosin heavy chain genes in the heart. Circulation 87: 1451–1460, 1993

    Google Scholar 

  25. Molkentin JD, Markham BE: An M-CAT binding factor and an RSRF-related A-rich binding factor positively regulate expression of the α-cardiac myosin heavy-chain gene in vivo. Mol Cell Biol 14: 5056–5065, 1994

    Google Scholar 

  26. Molkentin JD and Markham BE: Myocyte-specific enhancer-binding factor (MEF-2) regulates α-cardiac myosin heavy chain gene expression in vitro and in vivo. J Biol Chem 268: 19512–19520, 1993

    Google Scholar 

  27. Molkentin JD, Kalvakolanu DV, and Markham BE: Transcription factor GATA-4 regulates cardiac muscle-specific expression of the α-myosin heavy-chain gene. Mol Cell Biol 14: 4947–4957, 1994

    Google Scholar 

  28. Gupta MP, Gupta M, Zak R: An E-box/M-CAT hybrid motif and cognate binding protein(s) regulate the basal muscle-specific and cAMP-inducible expression of the rat cardiac α-myosin heavy chain gene. J Biol Chem 269: 29677–29687, 1994

    Google Scholar 

  29. Thompson WR, Nadal-Ginard B, Mahdavi V: A MyoD1-independent muscle-specific enhancer controls the expression of the beta-myosin heavy chain gene in skeletal and cardiac muscle cells. J Biol Chem 266: 22678–22688, 1991

    Google Scholar 

  30. Flink IL, Edwards JG, Bahl JJ, Liew CC, Sole M, Morkin E: Characterization of a strong positive cis-acting element of the human beta-myosin heavy chain gene in fetal rat heart cells. J Biol Chem 267: 9917–9924, 1992

    Google Scholar 

  31. Izumo S. and Mahdavi V: Thyroid hormone receptor alpha isoforms generated by alternative splicing differentially activate myosin HC gene transcription. Nature 334: 539–542, 1988

    Google Scholar 

  32. Flink IL, Morkin E: Interaction of thyroid hormone receptors with strong and weak cis-acting elements in the human ot-myosin heavy chain gene promoter. J Biol Chem 265: 11233–11237, 1990

    Google Scholar 

  33. Subramaniam A, Gulick J, Neumann J, Knotts S, Robbins J: Transgenic analysis of the thyroid-responsive elements in the α-cardiac myosin heavy chain gene promoter. J Biol Chem 268: 4331–4336, 1993

    Google Scholar 

  34. Nadal-Ginard B. and Mahdavi V: Molecular basis of cardiac performance. Plasticity of the myocardium generated through protein isoform switches. J Clin Invest 84: 1693–1700, 1989

    Google Scholar 

  35. Buttrick P M, Kaplan ML, Kitsis RN, Leinwand LA: Distinct behavior of cardiac myosin heavy chain gene constructs in vivo. Circ Res 72: 1211–1217, 1993

    Google Scholar 

  36. Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter WJ: Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry 18: 5294–5279, 1979

    CAS  PubMed  Google Scholar 

  37. Chomczynski P, Sacchi N: Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroformextraction. Anal Biochem 162: 156–159, 1987

    Article  CAS  PubMed  Google Scholar 

  38. Martin XJ, Schwartz K, Boheler KR: Characterization of a novel transcript of retroviral origin expressed in rat heart and liver. J Mol Cell Cardiol 27: 589–597, 1995

    Google Scholar 

  39. Simpson P: Norepinephrine-stimulated hypertrophy of culture rat myocardial cells is an α1-adrenergic response. J Clin Invest 72: 732–738, 1983

    Google Scholar 

  40. Petrou M, Wynne DG, Boheler KR, Yacoub MH. Clenbuterol induces hypertrophy of the latissimus dorsi muscle and heart in the rat with molecular and phenotypic changes. Circulation 92 [suppl II]: II-483-II-489, 1995

    Google Scholar 

  41. Boheler KR, Martin XJ, Buffing A, Bercovici J, Vermeulen JLM, Moorman AFM, and Schwartz K: Identification and examination of an endogenous antisense RNA from the β-myosin heavy chain gene in rat heart. (submitted) 1995

  42. Boheler K R, Chassagne C, Martin X, Wisnewsky C, Schwartz K: Cardiac expressions of a- and b-myosin heavy chains and sarcomeric oc-actins are regulated through transcriptional mechanisms. J Biol Chem 267: 12979–12985, 1992

    CAS  PubMed  Google Scholar 

  43. Moorman AFM, de Boer PAJ, Vermeulen JLM, Lamers WH: Practical aspects of radio-isotopic in situ hybridization on RNA. Histochem J 25: 251–266, 1993

    CAS  PubMed  Google Scholar 

  44. Boheler KR, Carrier L, de la Bastie D, Allen PD, Komajda M, Mercadier JJ, Schwartz K: Skeletal actin mRNA increases in the human heart during ontogenic development and is the major isoform of control and failing adult hearts. J Clin Invest 88: 323–330, 1991

    Google Scholar 

  45. Schwartz K, Carrier L, Chassagne C, Wisnewsky C, Boheler KR: Regulation of myosin heavy chain and actin isogenes during cardiac growth and hypertrophy. In: A. El Haj (ed.). Molecular Biology of Muscle. The Company of Biologists Limited, Cambridge, 1992, pp 265–272

    Google Scholar 

  46. McHugh KH and Lessard J: The developmental expression of the rat α-vascular and τ-enteric smooth muscle isoactins: Isolation and characterization of a rat τ-enteric actin cDNA. Mol Cell Biol 8: 5224–5231, 1988

    Google Scholar 

  47. Zakut R., Shani M, Givol D, Neuman S, Yaffe D, Nudel U: Nucleotide sequence of the rat skeletal muscle actin gene. Nature 298: 857–859, 1982

    Google Scholar 

  48. Long CS, Ordahl CP, Simpson PC: α1-Adrenergic receptor stimulation of sarcomeric actin isogene transcription in hypertrophy of cultured rat heart muscle cells. J Clin Invest 83: 1078–1082, 1989

    Google Scholar 

  49. Bishopric NH, Jayasena V, Webster KA: Positive regulation of the skeletal α-actin gene by Fos and Jun in cardiac myocytes. J Biol Chem 267: 25535–25540, 1992

    Google Scholar 

  50. Hewett TE, Grupp IL, Grupp G, Robbins J: α-Skeletal actin is associated with increased contractility in the mouse heart. Circ Res 74: 740–746, 1994

    Google Scholar 

  51. Boheler KR, Carrier L, Chassagne C, de la Bastie D, Mercadier JJ, Schwartz K: Regulation of myosin heavy chain and actin isogenes expression during cardiac growth. Mol Cell Biochem 104: 101–107, 1991

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pavillon Rambuteau, Groupe Hospitalier Pitié-Salpetrière, INSERM U153, 47-83 Bd de l'Hopital, 75630, Paris Cedex 13, France

    Xavier J. Martin

  2. National Heart and Lung Institute, the Departments of Cardiac Medicine Surgery, Imperial College, Dovehouse Street, SW3 6LY, London, UK

    Dylan G. Wynne & Kenneth R. Boheler

  3. National Heart and Lung Institute, the Departments of Cardiothoracic Surgery, Imperial College, Dovehouse Street, SW3 6LY, London, UK

    Peter E. Glennon

  4. Department of Anatomy and Embryology, Academic Medical Centre, Meibergdreef 15, 1105, AZ Amsterdam, The Netherlands

    Anton F. M. Moorman

Authors
  1. Xavier J. Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dylan G. Wynne
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Peter E. Glennon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anton F. M. Moorman
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kenneth R. Boheler
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Martin, X.J., Wynne, D.G., Glennon, P.E. et al. Regulation of expression of contractile proteins with cardiac hypertrophy and failure. Mol Cell Biochem 157, 181–189 (1996). https://doi.org/10.1007/BF00227897

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00227897

Key words

Search

Navigation