Project/Area Number |
25460175
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Environmental and hygienic pharmacy
|
Research Institution | Toho University |
Principal Investigator |
|
Project Period (FY) |
2013-04-01 – 2016-03-31
|
Project Status |
Completed (Fiscal Year 2015)
|
Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
Keywords | 核内受容体 / 転写因子 / 遺伝子発現調節 / 生体外異物 / Nuclear receptor / CAR / cytochrme P450 / cofactor / cytochrome P450 / 薬物代謝酵素 |
Outline of Final Research Achievements |
The CAR and PXR regulate various genes involved in xenobiotics and drug metabolism. In many cases, CAR/PXR share ligands termed dual ligands of CAR/PXR. First, we screened compound library to investigate dual ligand of CAR/PXR, we identified Nigramide J and T0901317, as a dual ligand of CAR/PXR. In this study, we established a tetracycline-inducible human CAR and stably human PXR-overexpressing HepG2 cell line (HepTR/hCAR/hPXR) to examine CAR/PXR dual ligands. We investigated the regulation of cytochrome P450 (CYP) 2B6, CYP2C9, CYP3A4, and UDP-glucuronosyl transferase, which are target genes of CAR/PXR, by dual ligands of CAR/PXR in two transfectants. We show that dual ligands of CAR/PXR show distinct gene regulation patterns by crosstalk between CAR and PXR. Furthermore, the two newly established cell lines are useful tools to investigate dual ligands of CAR/PXR.
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