Protein kinase Cθ is required for cardiomyocyte survival and cardiac remodeling

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 PKC θ isoform is expressed at considerable levels in the cardiac muscle in mouse, and...

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Bibliographic Details
Published in:Cell death & disease Vol. 1; no. 5; p. e45
Main Authors: Paoletti, R, Maffei, A, Madaro, L, Notte, A, Stanganello, E, Cifelli, G, Carullo, P, Molinaro, M, Lembo, G, Bouché, M
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 01.05.2010
Nature Publishing Group
Subjects:
631/443/592
631/45/607/275
692/699/75/74
Animals
Antibodies
Biochemistry
Biomedical and Life Sciences
Cardiomegaly - complications
Cardiomegaly - diagnostic imaging
Cardiomegaly - enzymology
Cardiomegaly - physiopathology
Cell Biology
Cell Count
Cell Culture
Cell Survival
Enzyme Activation
Fibroblasts - enzymology
Fibroblasts - pathology
Gene Deletion
Hemodynamics
Immunology
Isoenzymes - metabolism
Life Sciences
Mice
Mitogen-Activated Protein Kinases - metabolism
Myocardium - enzymology
Myocardium - pathology
Myocytes, Cardiac - enzymology
Myocytes, Cardiac - pathology
Original
original-article
Pressure
Protein Kinase C - metabolism
Protein Kinase C-theta
Ultrasonography
Ventricular Dysfunction, Left - complications
Ventricular Dysfunction, Left - diagnostic imaging
Ventricular Dysfunction, Left - enzymology
Ventricular Dysfunction, Left - physiopathology
Ventricular Remodeling - physiology
alpha1-adrenergic agonists
protein kinases C
cardiomyocyte survival
protein kinase C theta
dilated cardiomyopathy
ISSN:2041-4889, 2041-4889
Online Access:Get full text
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Summary: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 PKC θ 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 PKC θ in cardiac remodeling, we used PKC θ −/− mice. In vivo analyses of PKC θ −/− hearts showed that the lack of PKC θ 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 PKC θ −/− cardiomyocytes were less viable than wild-type cardiomyocytes, and, unlike wild-type cardiomyocytes, underwent programmed cell death upon stimulation with α 1-adrenergic agonists and hypoxia. Taken together, these results show that PKC θ 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.
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Current address: CNR-EMMA, Campus Adriano Buzzati-Traverso, Monterotondo, Rome, Italy
ISSN:2041-4889
2041-4889
DOI:10.1038/cddis.2010.24