WEKO3
アイテム
{"_buckets": {"deposit": "dfbcb495-723e-4955-92e5-7546e5d705f6"}, "_deposit": {"created_by": 11, "id": "3521", "owners": [11], "pid": {"revision_id": 0, "type": "depid", "value": "3521"}, "status": "published"}, "_oai": {"id": "oai:shiga-med.repo.nii.ac.jp:00003521", "sets": ["90"]}, "author_link": ["7850", "6550", "3686", "7856", "7855", "3688", "7854", "7857", "7853", "7858", "1939", "297", "6179", "7848", "6731", "1863", "7849", "7852", "7847", "7851"], "item_4_biblio_info_6": {"attribute_name": "書誌情報", "attribute_value_mlt": [{"bibliographicIssueDates": {"bibliographicIssueDate": "2020-03-16", "bibliographicIssueDateType": "Issued"}, "bibliographic_titles": [{}, {"bibliographic_title": "FASEB journal : official publication of the Federation of American Societies for Experimental Biology", "bibliographic_titleLang": "en"}]}]}, "item_4_creator_3": {"attribute_name": "著者別名", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "清水, 昭男"}], "nameIdentifiers": [{"nameIdentifier": "6731", "nameIdentifierScheme": "WEKO"}, {"nameIdentifier": "30769279", "nameIdentifierScheme": "e-Rad", "nameIdentifierURI": "https://kaken.nii.ac.jp/ja/search/?qm=30769279"}, {"nameIdentifier": "0000-0002-3393-6193", "nameIdentifierScheme": "ORCID", "nameIdentifierURI": "https://orcid.org/0000-0002-3393-6193"}]}, {"creatorNames": [{"creatorName": "佐藤, 朗"}], "nameIdentifiers": [{"nameIdentifier": "7847", "nameIdentifierScheme": "WEKO"}, {"nameIdentifier": "70464302", "nameIdentifierScheme": "e-Rad", "nameIdentifierURI": "https://kaken.nii.ac.jp/ja/search/?qm=70464302"}]}, {"creatorNames": [{"creatorName": "米野, 雅大"}], "nameIdentifiers": [{"nameIdentifier": "7848", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "豊田, 太"}], "nameIdentifiers": [{"nameIdentifier": "3688", "nameIdentifierScheme": "WEKO"}, {"nameIdentifier": "90324574", "nameIdentifierScheme": "e-Rad", "nameIdentifierURI": "https://kaken.nii.ac.jp/ja/search/?qm=90324574"}]}, {"creatorNames": [{"creatorName": "一杉, 正仁"}], "nameIdentifiers": [{"nameIdentifier": "6550", "nameIdentifierScheme": "WEKO"}, {"nameIdentifier": "90328352", "nameIdentifierScheme": "e-Rad", "nameIdentifierURI": "https://kaken.nii.ac.jp/ja/search/?qm=90328352"}, {"nameIdentifier": "0000-0001-5243-8766", "nameIdentifierScheme": "ORCID", "nameIdentifierURI": "https://orcid.org/0000-0001-5243-8766"}]}, {"creatorNames": [{"creatorName": "松浦, 博"}], "nameIdentifiers": [{"nameIdentifier": "3686", "nameIdentifierScheme": "WEKO"}, {"nameIdentifier": "60238962", "nameIdentifierScheme": "e-Rad", "nameIdentifierURI": "https://kaken.nii.ac.jp/ja/search/?qm=60238962"}, {"nameIdentifier": "0000-0003-1998-0996", "nameIdentifierScheme": "ORCID", "nameIdentifierURI": "https://orcid.org/0000-0003-1998-0996"}]}, {"creatorNames": [{"creatorName": "大野, 聖子"}], "nameIdentifiers": [{"nameIdentifier": "1939", "nameIdentifierScheme": "WEKO"}, {"nameIdentifier": "20610025", "nameIdentifierScheme": "e-Rad", "nameIdentifierURI": "https://kaken.nii.ac.jp/ja/search/?qm=20610025"}, {"nameIdentifier": "0000-0003-1209-8896", "nameIdentifierScheme": "ORCID", "nameIdentifierURI": "https://orcid.org/0000-0003-1209-8896"}]}, {"creatorNames": [{"creatorName": "堀江, 稔"}], "nameIdentifiers": [{"nameIdentifier": "297", "nameIdentifierScheme": "WEKO"}, {"nameIdentifier": "90183938", "nameIdentifierScheme": "e-Rad", "nameIdentifierURI": "https://kaken.nii.ac.jp/ja/search/?qm=90183938"}, {"nameIdentifier": "0000-0002-9029-2339", "nameIdentifierScheme": "ORCID", "nameIdentifierURI": "https://orcid.org/0000-0002-9029-2339"}]}, {"creatorNames": [{"creatorName": "扇田, 久和"}], "nameIdentifiers": [{"nameIdentifier": "6179", "nameIdentifierScheme": "WEKO"}, {"nameIdentifier": "50379236", "nameIdentifierScheme": "e-Rad", "nameIdentifierURI": "https://kaken.nii.ac.jp/ja/search/?qm=50379236"}, {"nameIdentifier": "0000-0001-6750-1668", "nameIdentifierScheme": "ORCID", "nameIdentifierURI": "https://orcid.org/0000-0001-6750-1668"}]}]}, "item_4_description_4": {"attribute_name": "抄録", "attribute_value_mlt": [{"subitem_description": "Brugada syndrome (BrS) is an inherited channelopathy responsible for almost 20% of sudden cardiac deaths in patients with nonstructural cardiac diseases. Approximately 70% of BrS patients, the causative gene mutation(s) remains unknown. In this study, we used whole exome sequencing to investigate candidate mutations in a family clinically diagnosed with BrS. A heterozygous 1616G\u003eA substitution (R539Q mutation) was identified in the transmembrane protein 168 (TMEM168) gene of symptomatic individuals. Similar to endogenous TMEM168, both TMEM168 wild-type (WT) and mutant proteins that were ectopically induced in HL-1 cells showed nuclear membrane localization. A significant decrease in Na+ current and Nav 1.5 protein expression was observed in HL-1 cardiomyocytes expressing mutant TMEM168. Ventricular tachyarrhythmias and conduction disorders were induced in the heterozygous Tmem168 1616G\u003eA knock-in mice by pharmacological stimulation, but not in WT mice. Na+ current was reduced in ventricular cardiomyocytes isolated from the Tmem168 knock-in heart, and Nav 1.5 expression was also impaired. This impairment was dependent on increased Nedd4-2 binding to Nav 1.5 and subsequent ubiquitination. Collectively, our results show an association between the TMEM168 1616G\u003eA mutation and arrhythmogenesis in a family with BrS.", "subitem_description_type": "Abstract"}]}, "item_4_description_42": {"attribute_name": "資源タイプ", "attribute_value_mlt": [{"subitem_description": "Journal Article", "subitem_description_type": "Other"}]}, "item_4_publisher_32": {"attribute_name": "出版者", "attribute_value_mlt": [{"subitem_publisher": " John Wiley \u0026 Sons, Inc."}]}, "item_4_relation_10": {"attribute_name": "PubMed番号", "attribute_value_mlt": [{"subitem_relation_type_id": {"subitem_relation_type_id_text": "32175648", "subitem_relation_type_select": "PMID"}}]}, "item_4_relation_11": {"attribute_name": "DOI", "attribute_value_mlt": [{"subitem_relation_name": [{"subitem_relation_name_text": "10.1096/fj.201902991R"}], "subitem_relation_type_id": {"subitem_relation_type_id_text": "https://doi.org/10.1096/fj.201902991R", "subitem_relation_type_select": "DOI"}}]}, "item_4_rights_12": {"attribute_name": "権利", "attribute_value_mlt": [{"subitem_rights": "© 2020 Federation of American Societies for Experimental Biology."}]}, "item_4_source_id_7": {"attribute_name": "ISSN", "attribute_value_mlt": [{"subitem_source_identifier": "1530-6860", "subitem_source_identifier_type": "ISSN"}]}, "item_access_right": {"attribute_name": "アクセス権", "attribute_value_mlt": [{"subitem_access_right": "metadata only access", "subitem_access_right_uri": "http://purl.org/coar/access_right/c_14cb"}]}, "item_creator": {"attribute_name": "著者", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "SHIMIZU, Akio"}], "nameIdentifiers": [{"nameIdentifier": "6731", "nameIdentifierScheme": "WEKO"}, {"nameIdentifier": "30769279", "nameIdentifierScheme": "e-Rad", "nameIdentifierURI": "https://kaken.nii.ac.jp/ja/search/?qm=30769279"}, {"nameIdentifier": "0000-0002-3393-6193", "nameIdentifierScheme": "ORCID", "nameIdentifierURI": "https://orcid.org/0000-0002-3393-6193"}]}, {"creatorNames": [{"creatorName": "ZANKOV, Dimitar Petrov"}], "nameIdentifiers": [{"nameIdentifier": "1863", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "SATO, Akira"}], "nameIdentifiers": [{"nameIdentifier": "7847", "nameIdentifierScheme": "WEKO"}, {"nameIdentifier": "70464302", "nameIdentifierScheme": "e-Rad", "nameIdentifierURI": "https://kaken.nii.ac.jp/ja/search/?qm=70464302"}]}, {"creatorNames": [{"creatorName": "KOMENO, Masahiro"}], "nameIdentifiers": [{"nameIdentifier": "7848", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "TOYODA, Futoshi"}], "nameIdentifiers": [{"nameIdentifier": "3688", "nameIdentifierScheme": "WEKO"}, {"nameIdentifier": "90324574", "nameIdentifierScheme": "e-Rad", "nameIdentifierURI": "https://kaken.nii.ac.jp/ja/search/?qm=90324574"}]}, {"creatorNames": [{"creatorName": "YAMAZAKI, Satoru"}], "nameIdentifiers": [{"nameIdentifier": "7849", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "MAKITA, Toshinori"}], "nameIdentifiers": [{"nameIdentifier": "7850", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "NODA, Taichi"}], "nameIdentifiers": [{"nameIdentifier": "7851", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "IKAWA, Masahito"}], "nameIdentifiers": [{"nameIdentifier": "7852", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "ASANO, Yoshihiro"}], "nameIdentifiers": [{"nameIdentifier": "7853", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "MIYASHITA, Yohei"}], "nameIdentifiers": [{"nameIdentifier": "7854", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "TAKASHIMA, Seiji"}], "nameIdentifiers": [{"nameIdentifier": "7855", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "MORITA, Hiroshi"}], "nameIdentifiers": [{"nameIdentifier": "7856", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "ISHIKAWA, Taisuke"}], "nameIdentifiers": [{"nameIdentifier": "7857", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "MAKITA, Naomasa"}], "nameIdentifiers": [{"nameIdentifier": "7858", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "HITOSUGI, Masahito"}], "nameIdentifiers": [{"nameIdentifier": "6550", "nameIdentifierScheme": "WEKO"}, {"nameIdentifier": "90328352", "nameIdentifierScheme": "e-Rad", "nameIdentifierURI": "https://kaken.nii.ac.jp/ja/search/?qm=90328352"}, {"nameIdentifier": "0000-0001-5243-8766", "nameIdentifierScheme": "ORCID", "nameIdentifierURI": "https://orcid.org/0000-0001-5243-8766"}]}, {"creatorNames": [{"creatorName": "MATSUURA, Hiroshi"}], "nameIdentifiers": [{"nameIdentifier": "3686", "nameIdentifierScheme": "WEKO"}, {"nameIdentifier": "60238962", "nameIdentifierScheme": "e-Rad", "nameIdentifierURI": "https://kaken.nii.ac.jp/ja/search/?qm=60238962"}, {"nameIdentifier": "0000-0003-1998-0996", "nameIdentifierScheme": "ORCID", "nameIdentifierURI": "https://orcid.org/0000-0003-1998-0996"}]}, {"creatorNames": [{"creatorName": "OHNO, Seiko"}], "nameIdentifiers": [{"nameIdentifier": "1939", "nameIdentifierScheme": "WEKO"}, {"nameIdentifier": "20610025", "nameIdentifierScheme": "e-Rad", "nameIdentifierURI": "https://kaken.nii.ac.jp/ja/search/?qm=20610025"}, {"nameIdentifier": "0000-0003-1209-8896", "nameIdentifierScheme": "ORCID", "nameIdentifierURI": "https://orcid.org/0000-0003-1209-8896"}]}, {"creatorNames": [{"creatorName": "HORIE, Minoru"}], "nameIdentifiers": [{"nameIdentifier": "297", "nameIdentifierScheme": "WEKO"}, {"nameIdentifier": "90183938", "nameIdentifierScheme": "e-Rad", "nameIdentifierURI": "https://kaken.nii.ac.jp/ja/search/?qm=90183938"}, {"nameIdentifier": "0000-0002-9029-2339", "nameIdentifierScheme": "ORCID", "nameIdentifierURI": "https://orcid.org/0000-0002-9029-2339"}]}, {"creatorNames": [{"creatorName": "扇田, 久和"}], "nameIdentifiers": [{"nameIdentifier": "6179", "nameIdentifierScheme": "WEKO"}, {"nameIdentifier": "50379236", "nameIdentifierScheme": "e-Rad", "nameIdentifierURI": "https://kaken.nii.ac.jp/ja/search/?qm=50379236"}, {"nameIdentifier": "0000-0001-6750-1668", "nameIdentifierScheme": "ORCID", "nameIdentifierURI": "https://orcid.org/0000-0001-6750-1668"}]}]}, "item_keyword": {"attribute_name": "キーワード", "attribute_value_mlt": [{"subitem_subject": "fatal ventricular arrhythmia", "subitem_subject_language": "en", "subitem_subject_scheme": "Other"}, {"subitem_subject": "sodium channel", "subitem_subject_language": "en", "subitem_subject_scheme": "Other"}, {"subitem_subject": "ubiquitination", "subitem_subject_language": "en", "subitem_subject_scheme": "Other"}]}, "item_language": {"attribute_name": "言語", "attribute_value_mlt": [{"subitem_language": "eng"}]}, "item_resource_type": {"attribute_name": "資源タイプ", "attribute_value_mlt": [{"resourcetype": "journal article", "resourceuri": "http://purl.org/coar/resource_type/c_6501"}]}, "item_title": "Identification of transmembrane protein 168 mutation in familial Brugada syndrome.", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "Identification of transmembrane protein 168 mutation in familial Brugada syndrome."}]}, "item_type_id": "4", "owner": "11", "path": ["90"], "permalink_uri": "http://hdl.handle.net/10422/00012644", "pubdate": {"attribute_name": "公開日", "attribute_value": "2020-04-20"}, "publish_date": "2020-04-20", "publish_status": "0", "recid": "3521", "relation": {}, "relation_version_is_last": true, "title": ["Identification of transmembrane protein 168 mutation in familial Brugada syndrome."], "weko_shared_id": -1}
Identification of transmembrane protein 168 mutation in familial Brugada syndrome.
http://hdl.handle.net/10422/00012644
http://hdl.handle.net/10422/000126445340513e-26fa-4a99-9c7e-41950816f6fb
Item type | 学術雑誌論文 / Journal Article(1) | |||||
---|---|---|---|---|---|---|
公開日 | 2020-04-20 | |||||
タイトル | ||||||
タイトル | Identification of transmembrane protein 168 mutation in familial Brugada syndrome. | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | fatal ventricular arrhythmia | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | sodium channel | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | ubiquitination | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
アクセス権 | ||||||
アクセス権 | metadata only access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
著者 |
SHIMIZU, Akio
× SHIMIZU, Akio× ZANKOV, Dimitar Petrov× SATO, Akira× KOMENO, Masahiro× TOYODA, Futoshi× YAMAZAKI, Satoru× MAKITA, Toshinori× NODA, Taichi× IKAWA, Masahito× ASANO, Yoshihiro× MIYASHITA, Yohei× TAKASHIMA, Seiji× MORITA, Hiroshi× ISHIKAWA, Taisuke× MAKITA, Naomasa× HITOSUGI, Masahito× MATSUURA, Hiroshi× OHNO, Seiko× HORIE, Minoru× 扇田, 久和 |
|||||
著者別名 |
清水, 昭男
× 清水, 昭男× 佐藤, 朗× 米野, 雅大× 豊田, 太× 一杉, 正仁× 松浦, 博× 大野, 聖子× 堀江, 稔× 扇田, 久和 |
|||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Brugada syndrome (BrS) is an inherited channelopathy responsible for almost 20% of sudden cardiac deaths in patients with nonstructural cardiac diseases. Approximately 70% of BrS patients, the causative gene mutation(s) remains unknown. In this study, we used whole exome sequencing to investigate candidate mutations in a family clinically diagnosed with BrS. A heterozygous 1616G>A substitution (R539Q mutation) was identified in the transmembrane protein 168 (TMEM168) gene of symptomatic individuals. Similar to endogenous TMEM168, both TMEM168 wild-type (WT) and mutant proteins that were ectopically induced in HL-1 cells showed nuclear membrane localization. A significant decrease in Na+ current and Nav 1.5 protein expression was observed in HL-1 cardiomyocytes expressing mutant TMEM168. Ventricular tachyarrhythmias and conduction disorders were induced in the heterozygous Tmem168 1616G>A knock-in mice by pharmacological stimulation, but not in WT mice. Na+ current was reduced in ventricular cardiomyocytes isolated from the Tmem168 knock-in heart, and Nav 1.5 expression was also impaired. This impairment was dependent on increased Nedd4-2 binding to Nav 1.5 and subsequent ubiquitination. Collectively, our results show an association between the TMEM168 1616G>A mutation and arrhythmogenesis in a family with BrS. | |||||
書誌情報 |
en : FASEB journal : official publication of the Federation of American Societies for Experimental Biology 発行日 2020-03-16 |
|||||
出版者 | ||||||
出版者 | John Wiley & Sons, Inc. | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 1530-6860 | |||||
PMID | ||||||
識別子タイプ | PMID | |||||
関連識別子 | 32175648 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.1096/fj.201902991R | |||||
関連名称 | 10.1096/fj.201902991R | |||||
権利 | ||||||
権利情報 | © 2020 Federation of American Societies for Experimental Biology. | |||||
資源タイプ | ||||||
内容記述タイプ | Other | |||||
内容記述 | Journal Article |