title: Emerin plays a crucial role in nuclear invagination and in the nuclear calcium transient.
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.
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.|Division of Cardiovascular Medicine, Kanazawa University Graduate School of Medicine, Takara-machi 13-1, Kanazawa, Ishikawa 920-8640, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Shimojima
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Yuasa
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Chikaaki
authors.initials: C
authors.lastname: Motoda
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Gakuto
authors.initials: G
authors.lastname: Yozu
authors.affiliation: Electron Microscope Laboratory, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nagai
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Ito
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Mark
authors.initials: M
authors.lastname: Lachmann
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Kashimura
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Takei
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Kusumoto
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kunitomi
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Hayashiji
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Seki
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Shugo
authors.initials: S
authors.lastname: Tohyama
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Hashimoto
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kodaira
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Egashira
authors.affiliation: Division of Cardiovascular Medicine, Kanazawa University Graduate School of Medicine, Takara-machi 13-1, Kanazawa, Ishikawa 920-8640, Japan.
authors.forename: Kenshi
authors.initials: K
authors.lastname: Hayashi
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.|Division of Cardiovascular Medicine, Kanazawa University Graduate School of Medicine, Takara-machi 13-1, Kanazawa, Ishikawa 920-8640, Japan.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Nakanishi
authors.affiliation: Division of Cardiovascular Medicine, Kanazawa University Graduate School of Medicine, Takara-machi 13-1, Kanazawa, Ishikawa 920-8640, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakata
authors.affiliation: Division of Cardiovascular Medicine, Kanazawa University Graduate School of Medicine, Takara-machi 13-1, Kanazawa, Ishikawa 920-8640, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Yamagishi
authors.affiliation: Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fukuda
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000804:Angiotensin II / Q000494:pharmacology; D000814:Aniline Compounds / Q000737:chemistry; D000818:Animals; D064752:Atrial Remodeling; D002118:Calcium / Q000378:metabolism*; D006332:Cardiomegaly / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000737:chemistry; D005786:Gene Expression Regulation; D006575:Heterocyclic Compounds, 3-Ring / Q000737:chemistry; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D020389:Muscular Dystrophy, Emery-Dreifuss / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009685:Nuclear Envelope / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020257:Ventricular Remodeling; D014966:Xanthenes / Q000737:chemistry
chemical_list: D000814:Aniline Compounds; D019332:Endothelin-1; C409648:Fluo 4; D005456:Fluorescent Dyes; D006575:Heterocyclic Compounds, 3-Ring; D008565:Membrane Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D014966:Xanthenes; C092710:emerin; D000804:Angiotensin II; D010656:Phenylephrine; D002118:Calcium