Study on the molecular basis of the response of the digestive tract evoked by nutrients/ food factors

营养素/食物因素引起消化道反应的分子基础研究

• 批准号: 18590220
• 负责人: GODA Toshinao
• 金额: $ 2.57万
• 依托单位: University of Shizuoka
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590220/
• 关键词: gene; transcriptional regulation; nutrition; nutrient signal; chromatin; histone code; small intestine; microarray; 発現調節; シグナル伝達

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.

1. 小肠中通过 TR、GR 和 RXR 进行转录控制：糖皮质激素受体 GR 和甲状腺激素受体 TR 的配体协同增强人肠细胞系 Caco-2 中果糖转运蛋白 GLUTS 的基因表达，同时伴随着 TR、GR、共激活子和乙酰化组蛋白 H3 和 H4 的结合增加。 GLUTS 基因的启动子区域。 MAP 激酶抑制剂使 TR 和 GR 去磷酸化，导致 TR 转录活性和 GR 核转位增强。 C2BBe1 细胞中的转染测定表明，细胞中检测到的视网膜脱氢酶足以将 9-顺式视黄醛转化为 RXR.2 的配体。通过碳水化合物信号转录控制碳水化合物消化/吸收相关基因：对高碳水化合物饮食大鼠的基因表达进行微阵列分析表明，空肠中 52 个转录/染色质相关基因上调。在喂食高碳水化合物饮食的小鼠中，空肠中蔗糖酶-异麦芽糖酶（SI）基因的表达增强，其中乙酰化组蛋白 H3 和 H4 以及假定的转录因子（即 Cdx-2 和 HNF-1）在 SI 基因近端区域的结合增强。给小鼠喂食果糖溶液导致SI基因近端区域乙​​酰化组蛋白H3和H4的结合增加。3．通过脂肪酸信号调控靶基因的表达：断奶大鼠饲喂辛酸或油酸引起空肠中PPAR、CBP/p300及其靶基因L-FABP和CRBPII的基因表达平行增加，当大鼠围产期小肠中突然诱导CRBPII基因时， CRBPII 基因近端区域的 RXR 和共激活因子以及乙酰化组蛋白 H3 和 H4 的增强。

项目成果

Changes on histone H3 modifications on the GLUT5 gene and its expression in Caco-2 cells co-treated with p44/42 inhibitor and glucocorticoid hormone.

p44/42抑制剂和糖皮质激素联合处理的Caco-2细胞中GLUT5基因组蛋白H3修饰及其表达的变化。

• 发表时间: 2008
• 期刊: Biochem. Biophys. Res. Commun. (印刷中)
• 作者: Mochizuki;K.;ら
• 通讯作者: ら

PPARα and PPARδ transactivity and p300 binding activity induced by arachidonic acid in colorectal cancer cell line Caco-2.

结直肠癌细胞系 Caco-2 中花生四烯酸诱导的 PPARα 和 PPARδ 反式活性和 p300 结合活性。

• 发表时间: 2008
• 期刊: J. Nutr. Sci. Vitaminol. 54(印刷中)
• 作者: Mochizuki;K.;ら
• 通讯作者: ら

The critical period for thyroid hormone responsiveness through thyroid hormone receptor isoform alpha-1 in the postnatal small intestine

出生后小肠中甲状腺激素受体亚型α-1对甲状腺激素反应的关键期

• 发表时间: 2007
• 期刊: Biochim.Biophys.Acta 1770
• 作者: Mochizuki;K.;他
• 通讯作者: 他

De-phosphorylation of TRα-1 by p44/42 MAPK inhibition enhances T_3-mediated GLUT5 gene expression in the intestinal cell line Caco-2 cells

p44/42 MAPK 抑制对 TRα-1 的去磷酸化增强肠细胞系 Caco-2 细胞中 T_3 介导的 GLUT5 基因表达

• 发表时间: 2007
• 期刊: Biochem.Biophys.Res.Commun 359
• 作者: Mochizuki;K.;他
• 通讯作者: 他

Selectivity of fatty acid ligands for PPARα awhich correlates both with binding to cis-element and DNA binding-independent transactivity in Caco-2 cells

PPARα 脂肪酸配体的选择性与 Caco-2 细胞中顺式元件的结合和 DNA 结合独立的反式活性相关

• 发表时间: 2006
• 期刊: Life Sci. 80
• 作者: Mochizuki;K.;他
• 通讯作者: 他