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Protein phosphorylation in isolated trabeculae from nonfailing and failing human hearts

  • Part III: Normal and Failing Myocardium
  • Published:
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Abstract

Disturbances in the cAMP production during β-adrenergic stimulation and alterations of Ca 2+ transport controlling proteins and their regulation in the sarcoplasmic reticulum might be involved in the pathogenesis of the failing human heart. Thus, we investigated the cAMP-mediated phosphorylation of phospholamban, troponin I and C-protein in electrically driven, intact isolated trabeculae carneae from nonfailing and failing (NYHA IV) human hearts in parallel to contractile properties on the same tissue samples. The increase in force of contraction induced by isoproterenol (0.2 μM) or pimobendan (100 μM), a phosphodiesterase inhibitor, was diminished in the failing human hearts compared to nonfailing hearts by 49% and 36%, respectively. Concomitantly the isoproterenol-induced phosphorylation (pmol P/mg homogenate protein) of phospholamban, troponin I and C-protein was reduced from 13.0 ± 2.4 (n = 4), 30.5 ± 1.5 (n = 5) and 11.0 ± 1.3 (n = 5) in the nonfailing heart to 5.2 ±0.6 (n = 13), 14.6 ± 2.2 (n = 16) and 7.1 ± 1.0 (n = 6) in the failing human heart, respectively. Pimobendan changed the phosphorylation state of these proteins similar to isoproterenol. The fact that combined addition of both agents or dibuturyl CAMP (1 mM) alone restored the phosphorylation capacity as observed in the control groups indicates that i) a reduced cAMP generation is related to the reduced phosphorylation of regulatory phosphoproteins located in the sarcoplasmic reticulum and contractile apparatus e.g. phospholamban, troponin I and C-protein, that ii) there is a relationship between protein phosphorylation state and contractile activity and that iii) no changes in the respective content of phosphoproteins are involved in the limitation of cAMP-mediated inotopic activity in the failing human heart. (Mol Cell Biochem 157: 171–179, 1996)

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Authors and Affiliations

  1. Forschungsschwerpunkt Kardiologie, Max-Delbrück-Zentrum für Molekulare Medizin, Robert-Rossle-Str. 10, 13125, Berlin, Germany

    Sabine Bartel, Ernst-Georg Krause & Peter Karczewski

  2. Abteilung Allgemeine Pharmakologie, Universitäts-Krankenhaus Eppendorf, Hamburg

    Birgitt Stein, Thomas Eschenhagen, Ulrike Mende & Hasso Scholz

  3. Institut für Pharmakologie und Toxikologie der Universität Münster, Germany

    Joachim Neumann & Wilhelm Schmitz

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  1. Sabine Bartel
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  2. Birgitt Stein
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  3. Thomas Eschenhagen
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  4. Ulrike Mende
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  5. Joachim Neumann
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  6. Wilhelm Schmitz
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  7. Ernst-Georg Krause
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  8. Peter Karczewski
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  9. Hasso Scholz
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Bartel, S., Stein, B., Eschenhagen, T. et al. Protein phosphorylation in isolated trabeculae from nonfailing and failing human hearts. Mol Cell Biochem 157, 171–179 (1996). https://doi.org/10.1007/BF00227896

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