Role of nutrients in the regulation of the expression of digestion/absorption-related genes

营养物质在消化/吸收相关基因表达调节中的作用

• 批准号: 09670075
• 负责人: GODA Toshinao
• 金额: $ 2.18万
• 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: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670075/
• 关键词: Lactase; Sucrase; Gene expression; Carbohydrate; Nuclear factor; Cdx-2; Glucose transporter; Development; 甲状腺ホルモン受容体; フルクトース; 日内リズム; ラクターゼ; 脂質

1. The 5' flanking regions of two representing disaccharidase genes, i.e., sucrase-isomaltase (SI) and lactase-phlorizin hydrolase (LPH) were cloned. In the 5' flanking region of both rat LPH and rat SI genes, common Cdx-2 binding elements were present and termed as CE-LPH1 and SIF1, respectively. In the 5' region of rat SI gene, a HNF1-binding element was also present which was associated with the diurnal variations in the SI gene expression.2. Developmental changes in the expressions of glucose transporters (GLUT5, SGLT1, GLUT2) and lactase were compared with those of nuclear factors in rat jejunum. After weaning, the mRNA levels of all types of glucose transporters were elevated, which was closely related with the rise in the expression of a thyroid hormone nuclear receptor (TR α-1). The decrease in the expression of LPH was accompanied by a decrease in the amounts of the nuclear factor binding to CE-LPH1.3. Oro-gastric feeding of a sucrose-containing diet to rats caused parallel in … More creases in SI and LPH mRNA levels within 3h, which were completely abolished by an injection of actinomycin D. A difference was observed in the site along the villus-crypt columns where the induction started ; the initial rise in SI mRNA level occurred at the lower villus, whereas that of LPH mRNA level occurred at more apical and broader locus of the villus.4. Among the monosaccharides tested, fructose gave rise to the most prominent increases in the transcripts of SI and LPH genes, which were accompanied by a coordinate rise in the transcripts of SGLT1 and GLUT5 genes. Feeding the diet containing glucose or α-methylglucoside (a non-metabolizable sugar) did not increase the transcript levels of SI, LPH and the intestinal hexose transporters. When a solution containing either fructose or glucose was simultaneously perfused into two consecutive cannulated and irrigated loops of jejunum, the loop perfused with fructose exhibited greater SI and GLUT5 mRNA levels than that perfused with glucose.5. Nuclear run-on assays revealed that fructose, but not glucose, increased the transcription of SI, LPH and GLUT5. Electromobility shift assays using the CE-LPH1 and the SIF1 elements revealed that nuclear extracts from the jejunum of rats fed the high-starch diet gave greater density of retarded bands than those of rats fed the low-starch diet. In addition, we found that force feeding a fructose diet gave rise to an increase in the binding of the dimeric nuclear protein (Cdx2) to the SIF1 element, which was reproduced by dephosphorylation of the nuclear protein. Less

1.两个代表性的双磷酸酶基因的5'侧翼区，即，蔗糖酶-异麦芽糖酶（SI）和乳糖酶-根皮苷水解酶（LPH）基因。在大鼠LPH和大鼠SI基因的5'侧翼区，存在共同的Cdx-2结合元件，分别称为CE-LPH 1和SIF 1。在大鼠SI基因5'端也存在HNF 1结合元件，该元件与SI基因表达的昼夜变化有关.比较了大鼠空肠中葡萄糖转运蛋白（GLUT 5，SGLT 1，GLUT 2）和乳糖酶表达的发育变化与核因子的变化。断奶后，各类型葡萄糖转运蛋白的mRNA水平均升高，这与甲状腺激素核受体（TR α-1）表达的升高密切相关。LPH表达的减少伴随着与CE-LPH 1结合的核因子的量的减少。对大鼠口胃喂食含蔗糖饲料， ...更多信息 3 h内SI和LPH mRNA水平升高，而注射放线菌素D可完全消除这一变化。在沿着绒毛-隐窝柱的诱导起始部位存在差异，SI mRNA水平的起始升高发生在绒毛下部，而LPH mRNA水平的起始升高发生在绒毛的更顶端和更宽的部位.在测试的单糖中，果糖引起SI和LPH基因转录物的最显著增加，这伴随着SGLT 1和GLUT 5基因转录物的协同增加。喂食含有葡萄糖或α-甲基葡萄糖苷（一种不可代谢的糖）的饲料不会增加SI、LPH和肠道己糖转运蛋白的转录水平。将含有果糖或葡萄糖的溶液同时灌注到两个连续的插管和冲洗的空肠袢中时，用果糖灌注的空肠袢比用葡萄糖灌注的空肠袢表现出更高的SI和GLUT 5 mRNA水平。核运行分析表明，果糖，而不是葡萄糖，增加SI，LPH和GLUT 5的转录。使用CE-LPH 1和SIF 1元素的电迁移率变化分析显示，从高淀粉饮食喂养的大鼠空肠的核提取物比低淀粉饮食喂养的大鼠的延迟带的密度更大。此外，我们发现，强制喂食果糖饮食引起的二聚体核蛋白（Cdx 2）的SIF 1元件，这是由核蛋白的去磷酸化再现的结合增加。少

项目成果

Goda, T.: "Regulation of the expression of digestion-absorption related genes in the small intestine."Nippon Nogeikkagaku Kaishi. 73. 520-522 (1999)

Goda, T.：“小肠中消化吸收相关基因表达的调节。”Nippon Nogeikkagaku Kaishi。

合田 敏尚: "管腔内基質と消化吸収-二糖類水解酵素"JJPEN輸液栄養. 21. 803-808 (1999)

Toshihisa Goda：“腔内基质和消化吸收-二糖水解酶”JJPEN输液营养学21。803-808（1999）。

田中竹美, ら: "食餌性糖質によるラクターゼ・フロリジン水解酵素(LPH)の発現誘導" 消化と吸収. 20. 65-69 (1997)

Takemi Tanaka 等人：“膳食碳水化合物诱导乳糖酶-根皮苷水解酶 (LPH) 表达”《消化和吸收》20. 65-69 (1997)。

Kishi, Kazuhiro et al: "Enhancement of sucrase-isomaltase gene expression induced by luminally acministered fructose in rat j ejunum"Journal of Nutritional Science and Vitaminology. 10. 8-12 (1999)

Kishi、Kazuhiro 等人：“大鼠空肠中腔内施用果糖诱导蔗糖酶-异麦芽糖酶基因表达的增强”营养科学与维生素学杂志。

岸 和廣 他: "スクラーゼ・イソマルタ-ゼ遺伝子発現の日内リズムと核内転写調節因子との関連"消化と吸収. 22. 72-74 (1999)

Kazuhiro Kishi 等人：“蔗糖酶和异麦芽糖酶基因表达与核转录调节因子的昼夜节律之间的关系”消化和吸收 22. 72-74 (1999)。