Intracellular renin inhibits mitochondrial permeability transition pore via activated mitochondrial extracellular signal-regulated kinase (ERK) 1/2 during ischemia in diabetic hearts 1

• Material Type: 博士論文
• ISSN: 1422-0067
• Title: Intracellular renin inhibits mitochondrial permeability transition pore via activated mitochondrial extracellular signal-regulated kinase (ERK) 1/2 during ischemia in diabetic hearts
• Volume: 19 1
• Author/Editor: 佐藤, 照盛
• Author Heading: 佐藤, 照盛
• Publication, Distribution, etc.: MDPI
• Publication Date: 2018
• Publication Date (W3CDTF): 2018
• Alternative Title: 糖尿病心において虚血中に細胞内レニンはミトコンドリア細胞外シグナル調節キナーゼ1/2の活性を介してミトコンドリア透過性遷移孔を阻害する
• Periodical title: International Journal of Molecular Sciences
• Degree grantor/type: 浜松医科大学
• Date Granted: 2018-03-13
• Date Granted (W3CDTF): 2018-03-13
• Dissertation Number: 甲第781号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第781号
• Text Language Code: eng
• Subject Heading: mitochondrial ERK1/2; diabetes mellitus; ischemia; intracellular renin; mitochondrial permeability transition pore
• Target Audience: 一般
• Note (General): doctoral; 医学系研究科; Although beneficial effects of non-secreting intracellular renin (ns-renin) against ischemia have been reported, the precise mechanism remains unclear. In this study, we investigated the roles of ns-renin and mitochondrial extracellular signal-related kinase (ERK) 1/2 on mitochondrial permeability transition pore (mPTP) opening during ischemia in diabetes mellitus (DM) hearts. When isolated hearts from Wistar rats (non-DM hearts) and Goto-Kakizaki rats (DM hearts) were subjected to ischemia for 70 min by left anterior descending coronary artery ligation, DM hearts exhibited higher left ventricular (LV) developed pressure and lower LV end-diastolic pressure than non-DM hearts, suggesting ischemic resistance. In addition, DM hearts showed increased intracellular renin (int-renin, including secreting and non-secreting renin) in the ischemic area, and a direct renin inhibitor (DRI; aliskiren) attenuated ischemic resistance in DM hearts. ERK1/2 was significantly phosphorylated after ischemia in both whole cell and mitochondrial fractions in DM hearts. In isolated mitochondria from DM hearts, rat recombinant renin (r-renin) significantly phosphorylated mitochondrial ERK1/2, and hyperpolarized mitochondrial membrane potential (DYm) in a U0126 (an inhibitor of mitogen-activated protein kinases/ERK kinases)-sensitive manner. R-renin also attenuated atractyloside (Atr, an mPTP opener)-induced DYm depolarization and Atr-induced mitochondrial swelling in an U0126-sensitive manner in isolated mitochondria from DM hearts. Furthermore, U0126 attenuated ischemic resistance in DM hearts, whereas it did not alter the hemodynamics in non-DMhearts. Our results suggest that the increased int-renin during ischemia may inhibit mPTP opening through activation of mitochondrial ERK1/2, which may be involved in ischemic resistance in DM hearts.
• DOI: info:doi/10.3390/ijms19010055; https://doi.org/info:doi/10.3390/ijms19010055
• Persistent ID (NDL): info:ndljp/pid/11278478; https://dl.ndl.go.jp/pid/11278478
• 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): 2019-05-06T10:27:56+09:00
• Date Created (W3CDTF): 2019-02-21
• 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://hdl.handle.net/10271/00003504; https://hama-med.repo.nii.ac.jp/records/3363
• 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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2023-12-09 再収集