| Project/Area Number |
14360069
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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 |
RYUICHIRO Sato The University of Tokyo, Graduate School of Agricultural and Life Sciences, Professor, 大学院・農学生命科学研究科, 教授 (50187259)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMIZU Makoto The University of Tokyo, 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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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥16,100,000 (Direct Cost: ¥16,100,000)
Fiscal Year 2004: ¥5,100,000 (Direct Cost: ¥5,100,000)
Fiscal Year 2003: ¥5,100,000 (Direct Cost: ¥5,100,000)
Fiscal Year 2002: ¥5,900,000 (Direct Cost: ¥5,900,000)
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| Keywords | FXR / BABP / IBAT / bile acid / CDCA / ABCG5 / ABCG8 / コレステロール / 小腸 / 排出トランスポーター / LXR / Caco-2 |
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| Research Abstract |
(1)Functions of the bile acid-binding protein
Based on the fact that both of the bile acid-binding protein (BABP) and FXR can bind bile acids, we examined whether BABP affects the FXR activity. In the culture cells stably expressing BABP, induction of the FXR activity was observed by chenodeoxycholic acid (CDCA) imported independently on the ileum bile acid transporter (IBAT), suggesting that the efficient exchange of bile acids between two proteins might exist. In the cells expressing IBAT transiently, the same phenomenon was observed. Furthermore, conjugated bile acids up taken by IBAT stimulated the FXR activity more significantly. It was thought that the more efficient absorption of conjugated bile acids than unconjugated ones by IBAT in the presence of BABP can explain this finding.
(2)Establishment of assay systems for evaluating the activation of FXR and the ligand-binding affinity
The current luciferase assay system enabled us to evaluate the FXR-stimulating effects of food ingredients. We succeeded to find out some factors that stimulate or decline the FXR activity among 160 kinds of food ingredients. We also established a new assay system to evaluate the ligand-binding affinity for food ingredients to the ligand-binding domain of FXR, which detect the activity of alkaline phosphatase fused to the nuclear receptor coactivator recruited by the binding of some factors to the ligand-binding domain. We have been analyzing the binding affinity of food ingredients using this assay system.
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