| Project/Area Number |
15K08271
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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 medical chemistry
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
MORISHIMA Keisuke 大阪大学, 大学院工学系研究科, 教授 (60359114)
YALIKUN Yaxiaer 大阪大学, 大学院工学系研究科, 特任助教 (30735064)
YAMAGUCHI Osamu 愛媛大学, 大学院医学系研究科, 教授 (90467580)
TSUKAMOTO Osamu 大阪大学, 大学院医学系研究科, 助教 (80589151)
KATO Hisakazu 大阪大学, 大学院医学系研究科, 助教 (30589312)
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| Research Collaborator |
YASHIROGI Shohei 大阪大学, 大学院生命機能研究科, 大学院生
YAZAWA Issei 大阪大学, 大学院生命機能研究科, 大学院生
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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 |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | AMPK / 微小管 / 介在板 / メカノストレス / 介在版 |
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| Outline of Final Research Achievements |
Recently, AMP-activated protein kinase (AMPK) has been reported to reshape cells by regulating cell polarity and division in addition to its canonical role in metabolism. We found that phosphorylated AMPK localized at the intercalated disks in adult mouse heart. We revealed CLIP170 and several other novel molecules as AMPK substrate at the intercalated disc. The inhibition of AMPK or CLIP S311A mutant increased the stability of microtubules near the cell-cell junction in cardiomyocytes. In order to reveal pathophysiological relevance of AMPK-CLIP signal in the heart, we made inducible heart-specific CLIP S311A overexpressing transgenic mice. In the pathological condition that was induced by doxorubicin injection, S311A mice exacerbated cardiac dysfunction with significant tissue fibrosis compared to the control. In conclusion, the regulation of microtubule dynamic instability by AMPK-CLIP signal is important for maintenance of heart function and the pathogenesis of heart diseases.
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