Elucidation of the pathogenesis of heart failure based on abnormal Ca2+ transport in myocardial mitochondria
| Project/Area Number |
16K19024
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
General pharmacology
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| Research Institution | Fukuoka University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | ミトコンドリア / カルシウムシグナル / 心不全 / 循環器 |
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| Outline of Final Research Achievements |
Mitochondria play an important role in regulating cell survival and death. We recently created a gene-deficient/tissue-specific overexpressing mice for the inner mitochondrial membrane calcium uniporter (MCU), which regulates Ca2+ uptake into mitochondria matrix, and the inner mitochondrial membrane Na+/Ca2+ exchanger (NCLX), which regulates Ca2+ excretion. Using these genetic modified mice, we investigated the mechanism of heart failure due to abnormal Ca2+ transport in myocardial mitochondria. As a result, we found that the disruption of maintenance of Ca2+ concentration in mitochondria is closely involved in the onset and progression of heart failure.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、MCU（Ca2+流入系）とNCLX（Ca2+排出系）のミトコンドリアCa2+輸送体遺伝子の欠損マウスを、本研究室独自に作製・解析し、心肥大・心不全発症機序におけるミトコンドリアCa2+輸送異常の関与をin vivoで証明した。現在使用されている心筋保護薬は、QOLの改善や医療費削減の観点から有用性が十分とは言えないのが現状である。本研究成果は、ミトコンドリアを標的とした新規心臓保護薬の開発に向けた新しいエビデンスとなりうる重要なものである。
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Report
(5 results)
Research Products
(24 results)
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[Journal Article] Reduced CaM Kinase II and CaM Kinase IV Activities Underlie Cognitive Deficits in NCKX2 Heterozygous Mice.2018
Author(s)
Moriguchi S, Kita S, Yabuki Y, Inagaki R, Izumi H, Sasaki Y, Tagashira H, Horie K, Takeda J, Iwamoto T, Fukunaga K.
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Journal Title
Mol Neurobiol.
Volume: 55(5)
Pages: 3889-3900
DOI
Related Report
Peer Reviewed
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[Journal Article] Blockade of the KATP channel Kir6.2 by memantine represents a novel mechanism relevant to Alzheimer's disease therapy.2016
Author(s)
Moriguchi S, Ishizuka T, Yabuki Y, Shioda N, Sasaki Y, Tagashira H, Yawo H, Yeh JZ, Sakagami H, Narahashi T, Fukunaga K.
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Journal Title
Mol Psychiatry.
Volume: 印刷中
Issue: 2
Pages: 211-221
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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