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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Vydáno v:	Cell death & disease Ročník 1; číslo 5; s. e45
Hlavní autoři:	Paoletti, R, Maffei, A, Madaro, L, Notte, A, Stanganello, E, Cifelli, G, Carullo, P, Molinaro, M, Lembo, G, Bouché, M
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 01.05.2010 Nature Publishing Group
Témata:	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
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Current address: CNR-EMMA, Campus Adriano Buzzati-Traverso, Monterotondo, Rome, Italy
ISSN:	2041-4889 2041-4889
DOI:	10.1038/cddis.2010.24