Regulation of the expression of carbohydrate digestion/absorption-related genes.
To explore the underlying molecular mechanism whereby nutrients modulate the expression of intestinal digestion/absorption-related genes, we have cloned the 5' flanking regions of two representing disaccharidase genes, i.e. sucrase-isomaltase (SI) and lactase-phlorizin hydrolase (LPH), and investigated whether the binding activity of putative common nuclear factor(s) binding to the cis-elements located in these regions is altered by dietary manipulations. Oro-gastric feeding of a sucrose-containing diet to rats caused parallel increases in SI mRNA and LPH mRNA levels within 3 h. Among the monosaccharides tested, fructose gave rise to the most prominent increase in the mRNA levels of SI and LPH genes, which were accompanied by a coordinate rise in the mRNA levels of two microvillar hexose transporters, i.e. SGLT1 and GLUT5. Nuclear run-on assays revealed that fructose, but not glucose, increased the transcription of SI, LPH and GLUT5. DNase I footprinting analysis of the rat LPH gene showed that the protected region conserved the same sequence as the cis-element (CE-LPH1) reported in the pig LPH gene. Electrophoretic mobility shift assay using CE-LPH1 and the related cis-element of SI gene (SIF1) 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. Force feeding a fructose diet gave rise to an increase in the binding of the dimeric nuclear protein (Cdx-2) to the SIF1 element. These results suggest that the cis-elements of CE-LPH1 and SIF1 might be involved in the carbohydrate-induced increases of the transcription of LPH and SI, presumably through a change in the expression and/or binding activity of Cdx-2.
Laboratory of Nutritional Physiology, School of Food and Nutritional Sciences, University of Shizuoka, Japan. gouda@fns1.u-shizuoka-ken.ac.jp.
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D000818:Animals; D000071616:CDX2 Transcription Factor; D004040:Dietary Carbohydrates / Q000008:administration & dosage / Q000378:metabolism*; D004063:Digestion / Q000235:genetics*; D005632:Fructose / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D051296:Glucose Transporter Type 5; D018398:Homeodomain Proteins / Q000378:metabolism*; D007408:Intestinal Absorption / Q000235:genetics*; D007421:Intestine, Small / Q000378:metabolism*; D010694:Lactase-Phlorizin Hydrolase / Q000235:genetics; D009004:Monosaccharide Transport Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013394:Sucrase-Isomaltase Complex / Q000235:genetics; D015534:Trans-Activators; D014158:Transcription, Genetic
D000071616:CDX2 Transcription Factor; D004040:Dietary Carbohydrates; D051296:Glucose Transporter Type 5; D018398:Homeodomain Proteins; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D005632:Fructose; D013394:Sucrase-Isomaltase Complex; D010694:Lactase-Phlorizin Hydrolase