TRPC3-Nox2 complex mediates doxorubicin-induced myocardial atrophy

• Material Type: 博士論文
• Title: TRPC3-Nox2 complex mediates doxorubicin-induced myocardial atrophy
• Author/Editor: 島内, 司
• Author Heading: 島内, 司
• Publication Date: 2018-02-28
• Publication Date (W3CDTF): 2018-02-28
• Alternative Title: TRPC3-Nox2複合体のドキソルビシン心筋症における役割
• Contributor: 筒井, 裕之; 塩瀬, 明; 今井, 猛
• Degree grantor/type: 九州大学
• Date Granted: 2018-02-28
• Date Granted (W3CDTF): 2018-02-28
• Dissertation Number: 甲第13904号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第13904号
• Text Language Code: eng
• Target Audience: 一般
• Note (General): Myocardial atrophy is a wasting of cardiac muscle due to hemodynamic unloading. Doxorubicin is a highly effective anticancer agent but also induces myocardial atrophy through a largely unknown mechanism. Here, we demonstrate that inhibiting transient receptor potential canonical 3 (TRPC3) channels abolishes doxorubicin-induced myocardial atrophy in mice. Doxorubicin increased production of ROS in rodent cardiomyocytes through hypoxic stress–mediated upregulation of NADPH oxidase 2 (Nox2), which formed a stable complex with TRPC3. Cardiomyocyte-specific expression of TRPC3 C-terminal minipeptide inhibited TRPC3-Nox2 coupling and suppressed doxorubicin-induced reduction of myocardial cell size and left ventricular (LV) dysfunction, along with its upregulation of Nox2 and oxidative stress, without reducing hypoxic stress. Voluntary exercise, an effective treatment to prevent doxorubicin-induced cardiotoxicity, also downregulated the TRPC3-Nox2 complex and promoted volume load–induced LV compliance, as demonstrated in TRPC3-deficient hearts. These results illustrate the impact of TRPC3 on LV compliance and flexibility and, focusing on the TRPC3-Nox2 complex, provide a strategy for prevention of doxorubicin-induced cardiomyopathy.; PubMed番号 : 28768915
• DOI: 10.15017/1931757; https://doi.org/10.15017/1931757
• Persistent ID (NDL): info:ndljp/pid/11116163; https://dl.ndl.go.jp/pid/11116163
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2018-07-03T21:49:10+09:00
• Date Created (W3CDTF): 2018-05-30
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://dx.doi.org/10.15017/1931757; http://hdl.handle.net/2324/1931757
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp

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