Understanding of the mechanism for the nuclear receptor-mediated hepatotoxicity and establishment of the prediction and evaluation system for the toxicity.
| Project/Area Number |
22390027
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
MIYATA Masaaki 東北大学, 大学院・薬学研究科, 助教 (90239418)
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| Co-Investigator(Renkei-kenkyūsha) |
YAMAZOE Yasushi 東北大学, 大学院・薬学研究科, 教授 (00112699)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2012: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2010: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
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| Keywords | 医薬品情報 / 安全性学 / 肝毒性 / 核内受容体 / 転写調節 / 動物試験代替法 / 薬剤性肝障害 / 細胞周期 / レポーターアッセイ / 脂質代謝 / 肝非実質細胞 / 炎症 / 肝発がん / PXR / CAR / 炎症シグナル |
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| Research Abstract |
In this study, we have investigated the functions of nuclear receptors CAR and PXR to understand their roles in hepatotoxicity. We have found that CAR transactivates human and mouse DHCR24 genes, that CAR inhibits PPARα-mediated transcription in mouse livers, and that PXR enhances the CAR- or PPARα-mediated proliferation of mouse hepatocytes. We have also established a reporter assay system to screen CAR activators.
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Report
(4 results)
Research Products
(34 results)
