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Increased Ca2+-sensitivity of the contractile apparatus in end-stage human heart failure results from altered phosphorylation of contractile proteins

van der Velden, J ; Papp, Z ; Zaremba, R ; Boontje, N M ; de Jong, J W ; Owen, V J ; Burton, P B J ; Goldmann, P ; Jaquet, K ; Stienen, G J M

Cardiovascular research, 2003-01, Vol.57 (1), p.37-47 [Periódico revisado por pares]

England

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  • Título:
    Increased Ca2+-sensitivity of the contractile apparatus in end-stage human heart failure results from altered phosphorylation of contractile proteins
  • Autor: van der Velden, J ; Papp, Z ; Zaremba, R ; Boontje, N M ; de Jong, J W ; Owen, V J ; Burton, P B J ; Goldmann, P ; Jaquet, K ; Stienen, G J M
  • Assuntos: Adult ; Aged ; Atrial Myosins - metabolism ; Blotting, Western ; Calcium - metabolism ; Cardiac Myosins - metabolism ; Case-Control Studies ; Cells, Cultured ; Contractile Proteins - metabolism ; Electrophoresis, Gel, Two-Dimensional ; Female ; Heart Failure - metabolism ; Humans ; Male ; Middle Aged ; Myocytes, Cardiac - metabolism ; Myosin Light Chains - metabolism ; Phosphorylation ; Protein Isoforms - metabolism ; Troponin I - metabolism ; Troponin T - metabolism
  • É parte de: Cardiovascular research, 2003-01, Vol.57 (1), p.37-47
  • Notas: ObjectType-Article-2
    SourceType-Scholarly Journals-1
    ObjectType-Feature-3
    ObjectType-Commentary-1
  • Descrição: The alterations in contractile proteins underlying enhanced Ca(2+)-sensitivity of the contractile apparatus in end-stage failing human myocardium are still not resolved. In the present study an attempt was made to reveal to what extent protein alterations contribute to the increased Ca(2+)-responsiveness in human heart failure. Isometric force and its Ca(2+)-sensitivity were studied in single left ventricular myocytes from non-failing donor (n=6) and end-stage failing (n=10) hearts. To elucidate which protein alterations contribute to the increased Ca(2+)-responsiveness isoform composition and phosphorylation status of contractile proteins were analysed by one- and two-dimensional gel electrophoresis and Western immunoblotting. Maximal tension did not differ between myocytes obtained from donor and failing hearts, while Ca(2+)-sensitivity of the contractile apparatus (pCa(50)) was significantly higher in failing myocardium (deltapCa(50)=0.17). Protein analysis indicated that neither re-expression of atrial light chain 1 and fetal troponin T (TnT) nor degradation of myosin light chains and troponin I (TnI) are responsible for the observed increase in Ca(2+)-responsiveness. An inverse correlation was found between pCa(50) and percentage of phosphorylated myosin light chain 2 (MLC-2), while phosphorylation of MLC-1 and TnT did not differ between donor and failing hearts. Incubation of myocytes with protein kinase A decreased Ca(2+)-sensitivity to a larger extent in failing (deltapCa(50)=0.20) than in donor (deltapCa(50)=0.03) myocytes, abolishing the difference in Ca(2+)-responsiveness. An increased percentage of dephosphorylated TnI was found in failing hearts, which significantly correlated with the enhanced Ca(2+)-responsiveness. The increased Ca(2+)-responsiveness of the contractile apparatus in end-stage failing human hearts cannot be explained by a shift in contractile protein isoforms, but results from the complex interplay between changes in the phosphorylation status of MLC-2 and TnI.
  • Editor: England
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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