| Project/Area Number |
11670076
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Environmental physiology (including Physical medicine and Nutritional physiology)
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| Research Institution | Siebold University of Nagasaki |
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Principal Investigator |
TAKASE Sachiko Dep.Nutrition, Siebold University of Nagasaki, Professor, 看護栄養学部・栄養健康学科, 教授 (10046196)
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| Co-Investigator(Kenkyū-buntansha) |
GODA Toshinao Dep.Food & Nutritional Sciences, University of Shizuoka, Associate Professor, 食品栄養科学部・栄養学科, 助教授 (70195923)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1999: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | CRBPII / intestine / gene expression / fatty acid / PPAR / coactivator / vitamin A / β-carotene dioxygenase / 細胞性レチノール結合たん白質TypeII / βカロテン開裂酵素 / レチノールエステル化酵素 |
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| Research Abstract |
We have reported that the gene expression of cellular retinol-binding protein, type II (CRBPII), which plays important roles in vitamin A uptake, transport and their metabolisms in small intestinal cells, is transcriptionally regulated by dietary fatty acids. In the present study, we further investigated the mechanism of transcriptional regulation of CRBPII gene and the effects on the intestinal vitamin A uptake and metabolisms modulated by fatty acids in the small intestine. We demonstrated in the cotransfection assay that the heterodimer of peroxisome proliferator-activated receptor α (PPARα) and retinoid X receptor (RXR) induced the rat CRBPII gene promoter's transactivity by binding to two putative nuclear receptor response elements (RXRE and RE3) in the presence of PPAR ligands such as linoleic acid and arachidonic acid. In the rat small intestine, not only PPARα but also PPARδ trasncripts was abundantly expressed. Therefore, in the next step, we examined the differences of ligand responsiveness between PPARα and PPARδ in the human small intestine-like cell lines Caco-2. In the one-hybrid assay, broad and great ligand responsiveness was seen in PPARα-mediated transactivity compared to PPARδ. Moreover, PPARα but not PPARδ preferentially interacted with coactivator p300, which was abundantly expressed in the rat small intestine. We further revealed that the increase of small intestinal CRBPII gene expression level by fatty acids led to an increase in the cellular uptake and metabolisms of vitamin A in the small intestine. These results suggest that the expressions of PPAR-dependent genes in the small intestine including CRBPII may be coordinately regulated by PPARα and PPARδ.
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