Abstract
Alteration of the nuclear Ca2+ transient is an early event in cardiac remodeling. Regulation of the nuclear Ca2+ transient is partly independent of the cytosolic Ca2+ transient in cardiomyocytes. One nuclear membrane protein, emerin, is encoded by EMD, and an EMD mutation causes Emery-Dreifuss muscular dystrophy (EDMD). It remains unclear whether emerin is involved in nuclear Ca2+ homeostasis. The aim of this study is to elucidate the role of emerin in rat cardiomyocytes by means of hypertrophic stimuli and in EDMD induced pluripotent stem (iPS) cell-derived cardiomyocytes in terms of nuclear structure and the Ca2+ transient. The cardiac hypertrophic stimuli increased the nuclear area, decreased nuclear invagination, and increased the half-decay time of the nuclear Ca2+ transient in cardiomyocytes. Emd knockdown cardiomyocytes showed similar properties after hypertrophic stimuli. The EDMD-iPS cell-derived cardiomyocytes showed increased nuclear area, decreased nuclear invagination, and increased half-decay time of the nuclear Ca2+ transient. An autopsied heart from a patient with EDMD also showed increased nuclear area and decreased nuclear invagination. These data suggest that Emerin plays a crucial role in nuclear structure and in the nuclear Ca2+ transient. Thus, emerin and the nuclear Ca2+ transient are possible therapeutic targets in heart failure and EDMD.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Active Transport, Cell Nucleus / drug effects
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Angiotensin II / pharmacology
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Aniline Compounds / chemistry
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Animals
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Atrial Remodeling
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Calcium / metabolism*
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Cardiomegaly / genetics*
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Cardiomegaly / metabolism
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Cardiomegaly / pathology
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Cytoplasm / drug effects
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Cytoplasm / metabolism
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Cytoplasm / ultrastructure
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Disease Models, Animal
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Endothelin-1 / pharmacology
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Fluorescent Dyes / chemistry
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Gene Expression Regulation
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Heterocyclic Compounds, 3-Ring / chemistry
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Humans
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Membrane Proteins / antagonists & inhibitors
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Membrane Proteins / genetics*
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Membrane Proteins / metabolism
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Muscular Dystrophy, Emery-Dreifuss / genetics*
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Muscular Dystrophy, Emery-Dreifuss / metabolism
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Muscular Dystrophy, Emery-Dreifuss / pathology
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Myocardium / metabolism*
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Myocardium / pathology
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Myocytes, Cardiac / drug effects
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Myocytes, Cardiac / metabolism*
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Myocytes, Cardiac / ultrastructure
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Nuclear Envelope / drug effects
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Nuclear Envelope / metabolism*
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Nuclear Envelope / ultrastructure
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Nuclear Proteins / antagonists & inhibitors
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Nuclear Proteins / genetics*
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Nuclear Proteins / metabolism
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Phenylephrine / pharmacology
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Primary Cell Culture
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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Rats
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Rats, Sprague-Dawley
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Ventricular Remodeling
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Xanthenes / chemistry
Substances
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Aniline Compounds
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Endothelin-1
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Fluo 4
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Fluorescent Dyes
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Heterocyclic Compounds, 3-Ring
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Membrane Proteins
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Nuclear Proteins
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RNA, Small Interfering
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Xanthenes
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emerin
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Angiotensin II
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Phenylephrine
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Calcium