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Downregulation of stanniocalcin 1 is responsible for sorafenib-induced cardiotoxicity
http://hdl.handle.net/10076/00020049
http://hdl.handle.net/10076/00020049a876ee8d-add2-4587-a7bc-f25279ad33fb
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
2014DM007 (1.8 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||||
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| 公開日 | 2021-12-13 | |||||||||||
| タイトル | ||||||||||||
| タイトル | Downregulation of stanniocalcin 1 is responsible for sorafenib-induced cardiotoxicity | |||||||||||
| 言語 | en | |||||||||||
| 言語 | ||||||||||||
| 言語 | eng | |||||||||||
| キーワード | ||||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | sorafenib | |||||||||||
| キーワード | ||||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | stanniocalcin 1 | |||||||||||
| キーワード | ||||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | cardiotoxicity | |||||||||||
| キーワード | ||||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | zebrafish | |||||||||||
| キーワード | ||||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | reactive oxygen species | |||||||||||
| 資源タイプ | ||||||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||||||
| 資源タイプ | doctoral thesis | |||||||||||
| アクセス権 | ||||||||||||
| アクセス権 | open access | |||||||||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||||||
| 著者 |
川端, 美湖
× 川端, 美湖
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| 抄録 | ||||||||||||
| 内容記述タイプ | Abstract | |||||||||||
| 内容記述 | Sorafenib is associated with adverse cardiac effects, including left ventricular dysfunction. However, the precise mechanism remains unclear. Here, we aimed to establish the genes responsible for this cardiotoxicity using zebrafish and human cardiomyocytes. Fluorescent cardiac imaging using pigmentless zebrafish with green fluorescent protein hearts revealed that the ventricular dimensions of the longitudinal axis with sorafenib were significantly shorter than those of the control group. Transcriptome analysis of their hearts revealed that stanniocalcin 1 (stc1) was downregulated by sorafenib. stc1 knockdown in zebrafish revealed that reduction of stc1 decreased the longitudinal dimensions of zebrafish ventricles, similar to that which occurs during sorafenib treatment. STC1 downregulation and cytotoxicity were also seen in human cardiomyocytes exposed to sorafenib. To clarify the molecular function of stc1 in sorafenib-induced cardiotoxicity, we focused on oxidative stress in cardiomyocytes treated with sorafenib. Reactive oxygen species (ROS) production significantly increased in both species of human cardiomyocytes and zebrafish exposed to sorafenib and STC1 knockdown compared with the controls. Finally, we found that forced expression of stc1 normalized impairment, decreasing the longitudinal dimensions in zebrafish treated with sorafenib. Our study demonstrated that STC1 plays a protective role against ventricular dysfunction and ROS overproduction, which are induced by sorafenib treatment. We discovered for the first time that STC1 downregulation is responsible for sorafenib-induced cardiotoxicity through activated ROS generation. | |||||||||||
| 内容記述 | ||||||||||||
| 内容記述タイプ | Other | |||||||||||
| 内容記述 | 本文/Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan | |||||||||||
| 内容記述 | ||||||||||||
| 内容記述タイプ | Other | |||||||||||
| 内容記述 | 37p | |||||||||||
| 書誌情報 |
発行日 2014-12-10 |
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| DOI | ||||||||||||
| 識別子タイプ | DOI | |||||||||||
| 関連識別子 | 10.1093/toxsci/kfu235 | |||||||||||
| フォーマット | ||||||||||||
| 内容記述タイプ | Other | |||||||||||
| 内容記述 | application/pdf | |||||||||||
| 著者版フラグ | ||||||||||||
| 出版タイプ | VoR | |||||||||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||||||
| 出版者 | ||||||||||||
| 出版者 | 三重大学 | |||||||||||
| 出版者（ヨミ） | ||||||||||||
| ミエダイガク | ||||||||||||
| 学位名 | ||||||||||||
| 学位名 | 博士(医学) | |||||||||||
| 学位授与機関 | ||||||||||||
| 学位授与機関識別子Scheme | kakenhi | |||||||||||
| 学位授与機関識別子 | 14101 | |||||||||||
| 学位授与機関名 | 三重大学 | |||||||||||
| 学位授与年月日 | ||||||||||||
| 学位授与年月日 | 2014-12-10 | |||||||||||
| 学位授与番号 | ||||||||||||
| 学位授与番号 | 甲医学第1692号 | |||||||||||
| ノート | ||||||||||||
| 資源タイプ（三重大） | ||||||||||||
| Doctoral Dissertation / 博士論文 | ||||||||||||
