| Budget Amount *help |
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
1. Transcriptional controls through TR, GR and RXR in the small intestine: Ligands of glucocorticoid hormone receptor GR and thyroid hormone receptor TR synergistically enhanced the gene expression of fructose transporter GLUTS in human intestinal cell line, Caco-2, which was accompanied by increases in the binding of TR, GR, coactivators and acetylated histones H3 and H4 on the promoter region of GLUTS gene. Dephosphorylation of TR and GR by MAP kinase inhibitor caused an enhancement of TR transcriptional activity and GR nuclear translocation. Transfection assay in C2BBe1 cell showed that retinal dehydrogenase detected in the cell was sufficient to convert 9-cis retinal to the ligand for RXR.
2. Transcriptional controls of carbohydrate digestion/absorption-related genes through a carbohydrate signal: Microarray analysis of the gene expression in rats fed a high carbohydrate diet showed that 52 transcription/chromatin-related genes were up-regulated in jejunum. In mice fed a high carbohydrate diet, the expression of sucrase-isomaltase (SI) gene was enhanced in jejunum, where the bindings of acetylatedhistones H3 and H4 and that of putative transcription factors, i.e., Cdx-2 and HNF-1, were enhanced on the proximal region of SI gene. Feeding fructose solution in mice caused an increase in the binding of acetylated histones H3 and H4 on the proximal region of SI gene.
3. Regulation of the expression of target genes through fatty acids signal: Feeding caprylic acid or oleic acid in weanling rats caused a parallel increase in the gene expression of PPAR, CBP/p300 and their target genes, i.e., L-FABP and CRBPII in the jejunum, When CRBPII gene is abruptly induced during the perinatal period in the small intestine of rats, the binding of RXR and coactivators as well as that of acetylated histones H3 and H4 was enhanced on the proximal region of CRBPII gene.
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