Potential therapeutic application of epigenetic mechanisms involved in the septic pathology
| Project/Area Number |
23590298
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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 pharmacology
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| Research Institution | University of Toyama |
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Principal Investigator |
HATTORI Yuichi 富山大学, 大学院医学薬学研究部(医学), 教授 (50156361)
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| Co-Investigator(Kenkyū-buntansha) |
YOKOO Hiroki 富山大学, 大学院医学薬学研究部(医学), 准教授 (30332894)
山本 誠士 富山大学, 大学院医学薬学研究部(医学), 助教 (10456361)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | エピジェネティクス / 脱アセチル化酵素 / 敗血症 / 急性肺傷害 / 炎症性サイトカイン / アポトーシス / 転写因子 / エピジェネティックス / レスベラトロール / SIRT1 |
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| Research Abstract |
Epigenetic programming, dynamically regulated by histone acetylation, may play a key role in the pathophysiology of sepsis. Mice with cecal ligation and puncture (CLP)-induced polymicrobial sepsis were used to examine whether histone deacetylase (HDAC) can contribute to sepsis-associated inflammation and apoptosis. Histone H3 and H4 acetylation levels were increased, and HDAC1, HDAC2, and HDAC3 protein levels were decreased in lungs after CLP. The results with HDAC inhibitors indicated that they are a unique agent to prevent cell apoptosis in sepsis at their doses that do not improve inflammatory features. This study also represents the down-regulation of HDACs in sepsis, but suggest that imbalance in histone acetylation may play a contributory role in expression or repression of genes involved in septic cell apoptosis.
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Report
(4 results)
Research Products
(16 results)
