The molecular mechanism of drug induced mitochondrial dysfunction focused on mitochondrial quality control system
| Project/Area Number |
15K08226
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
佐藤 岳哉 東北大学, 医学系研究科, 准教授 (10312696)
久志本 成樹 東北大学, 医学系研究科, 教授 (50195434)
斎藤 将樹 東北大学, 医学系研究科, 助教 (50400271)
柳澤 輝行 東北福祉大学, 健康科学部, 教授 (90133941)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | ミトコンドリア品質管理機構 / ミトコンドリアダイナミクス / 毒性薬理 / 活性酸素種 / AZT / ミトコンドリア / ミトコンドリア形態 / ROS / オートファジー / ＲOS / 薬物治療 / トキシコロジー / ミトコンドリア動態 |
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| Outline of Final Research Achievements |
We established a cell model of rat embryonic myoblasts in which azidothymidine triphosphate (AZT-TP), active metabolites of AZT, that is anti-HIV (human immunodeficiency virus) drug accumulates in a short time. Using this cell model, it was found that lethal cardiac dysfunction due to long-term administration of AZT is caused by accumulation of AZT-TP. Furthermore, as a detailed mechanism of cytotoxicity, accumulation of AZT-TP causes impairment of the mitochondrial quality control system, damage of mitochondrial electron transport chain and increasing reactive oxygen species (ROS) produciton in the cell, that induce apoptosis and cell death.
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Report
(4 results)
Research Products
(7 results)
