Absence of synemin in mice causes structural and functional abnormalities in heart
Autor: | Karla P. García-Pelagio, W. Jonathan Lederer, Christopher W. Ward, Robert J. Bloch, Humberto C. Joca, Ling Chen |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Aging Heart Ventricles 030204 cardiovascular system & hematology Left ventricular hypertrophy Article Electrocardiography Mice 03 medical and health sciences Sarcolemma 0302 clinical medicine Intermediate Filament Proteins Pressure medicine Animals Calcium Signaling Phosphorylation Muscular dystrophy Intermediate filament Myopathy Molecular Biology Costameres Chemistry Myocardium Synemin Skeletal muscle medicine.disease Myocardial Contraction Cell biology Cytoskeletal Proteins 030104 developmental biology medicine.anatomical_structure Desmin medicine.symptom Cardiology and Cardiovascular Medicine |
Zdroj: | Journal of Molecular and Cellular Cardiology. 114:354-363 |
ISSN: | 0022-2828 |
Popis: | Cardiomyopathies have been linked to changes in structural proteins, including intermediate filament (IF) proteins located in the cytoskeleton. IFs associate with the contractile machinery and costameres of striated muscle and with intercalated disks in the heart. Synemin is a large IF protein that mediates the association of desmin with Z-disks and stabilizes intercalated disks. It also acts as an A-kinase anchoring protein (AKAP). In murine skeletal muscle, the absence of synemin causes a mild myopathy. Here, we report that the genetic silencing of synemin in mice (synm −/−) causes left ventricular systolic dysfunction at 3 months and 12–16 months of age, and left ventricular hypertrophy and dilatation at 12–16 months of age. Isolated cardiomyocytes showed alterations in calcium handling that indicate defects intrinsic to the heart. Although contractile and costameric proteins remained unchanged in the old synm −/− hearts, we identified alterations in several signaling proteins (PKA-RII, ERK and p70S6K) critical to cardiomyocyte function. Our data suggest that synemin plays an important regulatory role in the heart and that the consequences of its absence are profound. |
Databáze: | OpenAIRE |
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