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Absence of synemin in mice causes structural and functional abnormalities in heart

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...

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Autores principales: García-Pelagio, Karla P., Chen, Ling, Joca, Humberto C., Ward, Christopher, Lederer, W. Jonathan, Bloch, Robert J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850968/
https://www.ncbi.nlm.nih.gov/pubmed/29247678
http://dx.doi.org/10.1016/j.yjmcc.2017.12.005
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author García-Pelagio, Karla P.
Chen, Ling
Joca, Humberto C.
Ward, Christopher
Lederer, W. Jonathan
Bloch, Robert J.
author_facet García-Pelagio, Karla P.
Chen, Ling
Joca, Humberto C.
Ward, Christopher
Lederer, W. Jonathan
Bloch, Robert J.
author_sort García-Pelagio, Karla P.
collection PubMed
description 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.
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spelling pubmed-58509682018-03-14 Absence of synemin in mice causes structural and functional abnormalities in heart García-Pelagio, Karla P. Chen, Ling Joca, Humberto C. Ward, Christopher Lederer, W. Jonathan Bloch, Robert J. J Mol Cell Cardiol Article 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. 2017-12-14 2018-01 /pmc/articles/PMC5850968/ /pubmed/29247678 http://dx.doi.org/10.1016/j.yjmcc.2017.12.005 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ).
spellingShingle Article
García-Pelagio, Karla P.
Chen, Ling
Joca, Humberto C.
Ward, Christopher
Lederer, W. Jonathan
Bloch, Robert J.
Absence of synemin in mice causes structural and functional abnormalities in heart
title Absence of synemin in mice causes structural and functional abnormalities in heart
title_full Absence of synemin in mice causes structural and functional abnormalities in heart
title_fullStr Absence of synemin in mice causes structural and functional abnormalities in heart
title_full_unstemmed Absence of synemin in mice causes structural and functional abnormalities in heart
title_short Absence of synemin in mice causes structural and functional abnormalities in heart
title_sort absence of synemin in mice causes structural and functional abnormalities in heart
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850968/
https://www.ncbi.nlm.nih.gov/pubmed/29247678
http://dx.doi.org/10.1016/j.yjmcc.2017.12.005
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