Protein kinase Cθ is required for cardiomyocyte survival and cardiac remodeling

R. Paoletti, A. Maffei, L. Madaro, A. Notte, E. Stanganello, G. Cifelli, P. Carullo, M. Molinaro, G. Lembo, M. Bouché

Research output: Contribution to journalArticlepeer-review

Abstract

Protein kinase Cs (PKCs) constitute a family of serine/threonine kinases, which has distinguished and specific roles in regulating cardiac responses, including those associated with heart failure. We found that the PKCθ isoform is expressed at considerable levels in the cardiac muscle in mouse, and that it is rapidly activated after pressure overload. To investigate the role of PKCθ in cardiac remodeling, we used PKCθ -/- mice. In vivo analyses of PKCθ -/- hearts showed that the lack of PKCθ expression leads to left ventricular dilation and reduced function. Histological analyses showed a reduction in the number of cardiomyocytes, combined with hypertrophy of the remaining cardiomyocytes, cardiac fibrosis, myofibroblast hyper-proliferation and matrix deposition. We also observed p38 and JunK activation, known to promote cell death in response to stress, combined with upregulation of the fetal pattern of gene expression, considered to be a feature of the hemodynamically or metabolically stressed heart. In keeping with these observations, cultured PKCθ -/- cardiomyocytes were less viable than wild-type cardiomyocytes, and, unlike wild-type cardiomyocytes, underwent programmed cell death upon stimulation with α1-adrenergic agonists and hypoxia. Taken together, these results show that PKCθ maintains the correct structure and function of the heart by preventing cardiomyocyte cell death in response to work demand and to neuro-hormonal signals, to which heart cells are continuously exposed.

Original languageEnglish
Article numbere45
JournalCell Death and Disease
Volume1
Issue number5
DOIs
Publication statusPublished - May 2010

Keywords

  • Alpha1-adrenergic agonists
  • Cardiomyocyte survival
  • Dilated cardiomyopathy
  • Protein kinase C theta
  • Protein kinases C

ASJC Scopus subject areas

  • Cell Biology
  • Immunology
  • Cancer Research
  • Cellular and Molecular Neuroscience

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