2007 Fiscal Year Final Research Report Summary
Intestinal tract as an organ for detoxification and excretion-Molecular analyses of its regulation by food factors
| 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)
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| Project Period (FY) |
2003 – 2007
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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
… More
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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Research Products
(112 results)
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[Journal Article] Keap1 regulates the constitutive expression of GST A1 during differentiation of Caco-2 cells.2008
Author(s)
Kusano, Y., Horie, S., Shibata, T., Satsu, H., Shimizu. M., ほか (Uchida, K : 12人中12番目)
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Journal Title
Biochemistry 47(23)
Pages: 6169-6177
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Keapl regulates the constitutive expression of GST Al during differentiation of Caco-2 cells.2008
Author(s)
Kusano, Y., Horie, S., Shibata, T., Satsu, H., Shimizu. M., et al.(Uchida, K. : 12人中12番目)
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Journal Title
Biochemistry 47(23)
Pages: 6169-6177
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Isolation of antioxidative phenolic glucosides from lemon juice and their suppressive effect on the exppression of blood adhesion molecules.2007
Author(s)
Miyake, Y., Mochizuki, M., Okada, M., Hiramitsu, M., Morimitsu, Y., Osawa, T.
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Journal Title
Biosci. Biotech. Biochem. 71(8)
Pages: 1911-1919
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Isolation of antioxidative phenolic glucosides from lemon juice and their suppressive effect on the expression of blood adhesion molecules.2007
Author(s)
Miyake, Y, Mochizuki, M., Okada, M., Hiramitsu, M., Morimitsu, Y., Osawa, T.
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Journal Title
Biosci. Biotech. Biochem. 71(8)
Pages: 1911-1919
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] TCDD-induced CYP1A1 expression, an index of dioxin toxicity, is suppressed bt flavonoids permeating the human intestinal Caco-2 cells monolayers.2006
Author(s)
Hamada, M., Satsu, H., Natsume, Y., Nishiumi, S., m Fukuda, I., Ashida, H., Shimizu, M.
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Journal Title
J. Agric. Food Chem. 54(23)
Pages: 8891-8898
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Induction by activated macrophage-like THP-1 cells of apoptotic and necrotic fcell death in intestinal epithelial Caco-2 monolayers via tumor necrosis factor-alpha.2006
Author(s)
Satsu, H., Ishimoto, Y., Nakano, T., Mochizuki, T., Iwanaga, T., Shimizu, M.
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Journal Title
Exp. Cell Res. 312 (19)
Pages: 3909-3919
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Oral exposure to cadmium chloride triggers and acute inflammatory response in the intestines of mice, initiated by over-expression of tissue macrophage inflammatory protein-2mRNA.2006
Author(s)
Zhao, Z., Hyun, J-S., Satsu, H., Kakuta, S., Shimizu, M.
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Journal Title
Toxic. Lett. 164
Pages: 144-154
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] TCDD-induced CYP1A1 expression, an index of dioxin toxicity, is suppressed by flavonoids permeating the human intestinal Caco-2 cells monolayers.2006
Author(s)
Hamada, M., Satsu, H., Natsume, Y, Nishiumi, S., Fukuda, I., Ashida, H., Shimizu, M.
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Journal Title
J. Agric. Food Chem. 54(23)
Pages: 8891-8898
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Induction by activated macrophage-like THP-1 cells of apoptotic and necrotic cell death in intestinal epithelial Caco-2 monolayers via tumor necrosis factor-alpha.2006
Author(s)
Satsu, H., Ishimnoto, Y, Nakano, T., Mochizuki, T., Iwanaga, T., Shimizu, M.
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Journal Title
Exp. Cell Res. 312 (19)
Pages: 3909-3919
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Oral exposure to cadmium chloride triggers and acute inflammatory response in the intestines of mice, initiated by over-expression of tissue macrophage inflammatory protein-2mRNA2006
Author(s)
Zhao, Z., Hyun, J-S., Satsu, H., Kakuta, S., Shitnizu, M.
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Journal Title
Toxic. Lett. 164
Pages: 144-154
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Evaluation of intestinal dioxin permeability by using human intestinal Caco-2 cell monolayers.2003
Author(s)
Natsume, Y., Satsu, H., Hatsugai, Y., Watanabe, H., Sato, R., et al. (Shimizu, M. : 8人中8番目)
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Journal Title
Food Sci. Technol. Res. 9(4)
Pages: 364-366
Description
「研究成果報告書概要(欧文)」より
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[Presentation] ケルセチンが腸管上皮に与える影響2008
Author(s)
夏目やよい, 伊藤真也, 門田幸二, 藤澤正彦, 薩秀夫, 戸塚護, 清水誠
Organizer
日本農芸化学会2008年度大会
Place of Presentation
名古屋
Year and Date
20080326-20080329
Description
「研究成果報告書概要(和文)」より
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