Molecular mechanisms of the transporters involved in the intestinal cell responses to xenobiotics and regulation of the transporters by food factors
| Project/Area Number |
12460055
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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 |
食品科学・栄養科学
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| Research Institution | THE UNIVERSITY OF TOKYO |
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Principal Investigator |
SHIMIZU Makoto Graduate School of Agricultural and Life Sciences, Professor, 大学院・農学生命科学研究科, 教授 (30114507)
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| Co-Investigator(Kenkyū-buntansha) |
SATO Ryuichiro Graduate School of Agricultural and Life Sciences, Associate professor, 大学院・農学生命科学研究科, 助教授 (50187259)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥14,200,000 (Direct Cost: ¥14,200,000)
Fiscal Year 2002: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2001: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2000: ¥8,600,000 (Direct Cost: ¥8,600,000)
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| Keywords | Intestinal epithelial cell / Barrier function / Transporter / P-glycoprotein / Xenobiotics / Taurine / Food factors / 機能性食品 |
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| Research Abstract |
Mechanisms for the transport of xenobiotics across the intestinal epithelial cell monolayers were investigated from the viewpoints of transporter and barrier functions. Characteristics of P-glycoprotein (P-gp) which is involved in the efflux of xenobiotics, and those of taurine transporter (Tau-TP) which is involved in the detoxification of cells were studied by using a cultured intestinal epithelial cell model. Methods to evaluate these transporter activities were first established by using a human intestinal epithelial Caco-2 cells. Effects of external factors such as xenobiotics and food factors on the activities of P-gp and Tau-TP were then studied. Tributyltin(TBT), an endocrine disrupting chemical, was toxic to Caco-2 cells, but up-regulation of P-gp by a long-term treatment with TBT was observed. This up-regulation was accompanied by the increase in the mRNA level. Tau-TP was up-regulated by osmotic stresses and cytokine stimulation, but was not significantly influenced by xenobiotic treatment. Long-term and short-term effects of food factors on these transporters were investigated. Vegetable extracts including the extract of bitter melon (Nigauri) markedly inhibited the activity of P-gp. The active substances were isolated and purified from the Nigauri extract. Characterization of the material is now in progress. Sesame seeds extract inhibited the Tau-TP, and the inhibitory substance was identified as lysophosphatidylcholine. The possible mechanisms for this inhibition was also studied.
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Report
(4 results)
Research Products
(6 results)
