| Project/Area Number |
24659380
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Yamagata University |
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Principal Investigator |
KUBOTA Isao 山形大学, 医学部, 教授 (30161673)
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| Co-Investigator(Kenkyū-buntansha) |
SHISHIDO Tetsuro 山形大学, 医学部, 助教 (60400545)
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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 |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 慢性心不全 / 胎児型遺伝子 / アセチル化 / クロマチン |
|---|
| Research Abstract |
High Mobility Group Box 1 (HMGB1) is a nuclear DNA-binding protein that has multiple functions, however little is known about the effects of nuclear HMGB1 on fetal gene expressions under hypertrophic stimulation. We observed decreased nuclear HMGB1 expression in human failing hearts and pressure overloaded mice heart. Nuclear HMGB1 decreased in response to endothelin-1 (ET-1) or angiotensin II (ATII) stimulation in cardiomyocytes, where nuclear HMGB1 was acetylated and translocated to the cytoplasm. Overexpression of nuclear HMGB1 attenuated ET-1 or ATII induced fetal gene expression such as ANP and BNP and induction of cardiomyocyte hypertrophy. These results suggest that the maintenance of stable nuclear HMGB1 levels prevents hypertrophy and heart failure.
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