Protein kinase C contributes to the maintenance of contractile force in human ventricular cardiomyocytes

Andrea Molnár, Attila Borbély, Dániel Czuriga, Siket M. Ivetta, Szabolcs Szilágyi, Zita Hertelendi, Enikö T. Pásztor, Ágnes Balogh, Zoltán Galajda, Tamás Szerafin, Kornelia Jaquet, Zoltán Papp, István Édes, Attila Tóth

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10 Citations (Scopus)

Abstract

Prolonged Ca2+ stimulations often result in a decrease in contractile force of isolated, demembranated human ventricular car-diomyocytes, whereas intact cells are likely to be protected from this deterioration. We hypothesized that cytosolic protein kinase C (PKC) contributes to this protection. Prolonged contracture (10 min) of demembranated human cardiomyocytes at half-maximal Ca2+ resulted in a 37 ± 5% reduction of active force (p < 0.01), whereas no decrease (2 ± 3% increase) was observed in the presence of the cytosol (reconstituted myocytes). The PKC inhibitors GF 109203X and Gö 6976 (10 μmol/liter) partially antagonized the cytosol-mediated protection (15 ± 5 and 9 ± 2% decrease in active force, p < 0.05). Quantitation of PKC isoform expression revealed the dominance of the Ca2+-dependent PKCα over PKCδ and PKCε (189 ± 31, 7 ± 3, and 7 ± 2 ng/mg protein, respectively). Ca2+ stimulations of reconstituted human cardiomyocytes resulted in the translocation of endogenous PKCα, but not PKCβ1, δ, and ε from the cytosol to the contractile system (PKCα association: control, 5 ± 3 arbitrary units; +Ca 2+,39 ± 8 arbitrary units; p < 0.01, EC50,ca = 645 nmol/liter). One of the PKCα-binding proteins were identified as the thin filament regulatory protein cardiac troponin I (Tnl). Finally, the Ca 2+-dependent interaction between PKCα and Tnl was confirmed using purified recombinant proteins (binding without Ca2+ was only 28 ± 18% of that with Ca2+). Our data suggest that PKCα translocates to the contractile system and anchors to TnI in a Ca2+ -dependent manner in the human heart, contributing to the maintenance ofcontractile force.

Original languageEnglish
Pages (from-to)1031-1039
Number of pages9
JournalJournal of Biological Chemistry
Volume284
Issue number2
DOIs
Publication statusPublished - Jan 9 2009

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Molnár, A., Borbély, A., Czuriga, D., Ivetta, S. M., Szilágyi, S., Hertelendi, Z., Pásztor, E. T., Balogh, Á., Galajda, Z., Szerafin, T., Jaquet, K., Papp, Z., Édes, I., & Tóth, A. (2009). Protein kinase C contributes to the maintenance of contractile force in human ventricular cardiomyocytes. Journal of Biological Chemistry, 284(2), 1031-1039. https://doi.org/10.1074/jbc.M807600200