| Project/Area Number |
18K19435
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 48:Biomedical structure and function and related fields
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| Research Institution | Jikei University School of Medicine |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
三尾 寧 東京慈恵会医科大学, 医学部, 教授 (00266686)
立花 利公 東京慈恵会医科大学, 医学部, 教授 (80163476)
岩本 武夫 東京慈恵会医科大学, 医学部, 教授 (90568891)
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| Project Period (FY) |
2018-06-29 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | ミトコンドリア / 心筋 / 張力 / 過伸展 / 乳頭筋 / 心筋過伸展 / メカノストレス |
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| Outline of Final Research Achievements |
We performed acute overstretch on cardiac papillary muscle to investigate the mechanisms in morphological changes in mitochondria. We overstretched right ventricle papillary muscle within 2 seconds. We analyzed the morphological changes using a Transmission electron microscopy (TEM). In TEM study, inner mitochondrial empty space was found after overstretch, indicating that inner mitochondria cristae were susceptible to deterioration. We investigated the effect of 1) overstretch release, 2) changes in Ca concentrations and 3) inhibiting mPTP (mitochondrial permeability transition pore) on acute overstretch. Releasing overstretch and changes in Ca concentration did not alter the inner mitochondrial collapsing. The inner mitochondrial collapsing was 20% reduced by inhibiting mPTP. It indicates that the mitochondrial collapsing was partly due to by Ca entering to mitochondrial inner space through mPTP.
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| Academic Significance and Societal Importance of the Research Achievements |
これまで経験的に知られていた心筋過伸展の分子メカニズムの一部を解明した。今後は病態時心筋の過伸展による影響を検討する。このことは、心不全の発症メカニズムを探る貴重なデータになると確信している。過伸展による微細形態構造変化への影響は未知な部分が多いため、今後の研究で心不全治療や抑制を来す、新たなターゲットとなる分子機構や創薬に繋がると思われる。心移植になる前の予防にも重要であると考える。
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