| Project/Area Number |
20590142
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Shinshu University |
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Principal Investigator |
MATSUNAGA Tamihide Shinshu University, 大学院・薬学研究科, 教授 (40209581)
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| Co-Investigator(Kenkyū-buntansha) |
OHMORI Shigeru 信州大学, 医学部・附属病院, 教授 (70169069)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2009: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2008: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
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| Keywords | 薬物動態 / 代謝学 / ヒト胎児 / 肝細胞 / リファンピシン / 転写活性 / コアクチベーター / コリプレッサー / 低酸素 / 低酸素誘導因子 / ヒト胎児肝細胞 / CYP3A4 / pregnane X receptor / 転写因子 / hepatocyte nuclear factor 4α / peroxisome proliferator activated receptor γ coactivator 1α / 薬物代謝酵素 / シトクロムP450 / CYP3A / 妊婦 / 胎児 / 薬物動態予測モデル / 胚性幹細胞 / デスフェロキサミン |
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| Research Abstract |
In HFL cells overexpressed PXR, RIF-mediated CYP3A4 induction was insufficient compared with HepG2 cells. Lower expression of HNF4α and PGC1α might impair RIF-mediated CYP3A4 induction in HFL cells. The expression levels of CYP3A4, CYP3A7 and VEGF mRNAs were significantly increased by DFO. The expression levels of CYP3A4 and CYP3A7 mRNAs in HFL cells were reduced by hypoxia (3% O_2), although the expression level of VEGF mRNA was enhanced. These results suggest that character of immature liver cells such as HFL cells with regard to CYP expression is different from that of highly differentiated human hepatocytes.
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