| Project/Area Number |
15108002
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| Research Category |
Grant-in-Aid for Scientific Research (S)
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| Allocation Type | Single-year Grants |
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| Research Field |
Food science
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| Research Institution | The University of Tokyo |
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Principal Investigator |
SHIMIZU Makoto The University of Tokyo, Graduate School of Agricultural and Life Sciences, Professor (30114507)
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| Co-Investigator(Kenkyū-buntansha) |
OSAWA Toshihiko Nagoya University, Graduate School of Bioagricultural Sciences, Professor (00115536)
UCHIDA Koji Nagoya University, Graduate School of Bioagricultural Sciences, Associate professor (40203533)
SATSU Hideo The University of Tokyo, Graduate School of Agricultural and Life Sciences, Assistant (80323484)
佐藤 隆一郎 東京大学, 大学院・農学生命科学研究科, 教授 (50187259)
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| Project Period (FY) |
2003 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥109,460,000 (Direct Cost: ¥84,200,000、Indirect Cost: ¥25,260,000)
Fiscal Year 2007: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2006: ¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000)
Fiscal Year 2005: ¥21,970,000 (Direct Cost: ¥16,900,000、Indirect Cost: ¥5,070,000)
Fiscal Year 2004: ¥22,620,000 (Direct Cost: ¥17,400,000、Indirect Cost: ¥5,220,000)
Fiscal Year 2003: ¥26,520,000 (Direct Cost: ¥20,400,000、Indirect Cost: ¥6,120,000)
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| Keywords | intestines / intestinal epithelial cell / detoxification enzymes / efflux transporter / food factors / Caco-2 |
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| Research Abstract |
Phase 1 enzymes (CYP etc.), Phase 2 enzymes (UGT etc.), and Phase 3 transporters (MDR, MRP etc.) are involved in detoxification and excretion functions of the gut. Screening and molecular analyses of the food factors which regulate these functions were performed in this study. Regulatory factors which directly affect MDR1 were searched in a variety of food materials by using in vitro experimental systems with human intestinal epithelial cells. 2-monopalmitate, for example, was identified as a dietary factor which inhibit MDR1 activity. Food factors that would activate a nuclear receptor PXR were searched by using reporter assay, because PXR is known to be involved in the regulation of detoxification. Certain flavonoids and terpenoids were found to activate PXR, thereby stimulating the expression of MDR1 at mRNA, protein and activity levels. We also found certain flavonoids and terpenoids suppressed the AhR-mediated and PXR-mediated expression of Phase 1 enzymes, respectively. Phase 2 e
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nzymes were also found to be regulated by flavonoids, terpenoids, amino acids, isoflavones and their metabolites. Induction by food factors of gene expression for detoxification enzymes such as CYP1A1, UGT1A1, MDR1 and MRP2 showed various patterns depending on the food factors. This suggests that food factors diversely and cooperatively affect the detoxification and efflux processes in the gut. Direct binding of food factors with certain transcription factors was observed to be involved in this detoxification process, transfer of the transcription factors to the nuclei being accompanied with this binding. We have also found that the detoxification system plays an important role in the expression of physiologic functions of food substances, suggesting that the detoxificating enzymes are not only for the detoxification and elimination of harmful substances, but also for enhancing the physiologic functions of food factors. The importance of dietary substances in regulating the intestinal barrier system by stimulating the detoxification system is also suggested by this project. Less
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