| Project/Area Number |
24790734
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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 |
Circulatory organs internal medicine
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| Research Institution | Akita University |
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Principal Investigator |
KIMURA Hirotaka 秋田大学, 医学(系)研究科(研究院), 非常勤講師 (30382899)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | PIK3C3 / 心肥大 / 心不全 / 心筋症 / ユビキチン化 / Vps34 / Pik3c3 |
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| Research Abstract |
We generated cardiomyocyte-specific Pik3c3 knockout (Pik3c3 KO) mice. Pik3c3 KO mice spontaneously developed severe cardiac hypertrophy, dysfunction of contractility, ventricular arrhythmias and sudden death. In Pik3c3 KO hearts, levels of phosphatidylinositol 3-phosphate (PI3P) were reduced. Electronmicroscopic analysis demonstrated that autophagosome was accumulated. Isolated cardiomyocytes were hypertrophic and protein aggregates were deposited in myocardium in the absence of Pik3c3 while proteasome function was normal. This aggregate included proteins degraded via vesicular trafficking, suggesting that Pik3c3 might regulate transport of polyubiquitinated proteins in vesicular trafficking. Similar protein deposition was detected in human cardiac specimen from cases with a heart disease. These findings implied that PIK3C3 deficiency might cause cardiac hypertrophy and heart failure in human.
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