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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 |
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| 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 |
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| 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 |
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| 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 | |||||
