Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.108 (lactase)
 2,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The promoter of the pig lactase-phlorizin hydrolase was cloned and showed to be functional in the human intestinal cell line Caco2. The proximal promoter was analyzed for binding of nuclear proteins from small intestine and liver. DNase I footprinting and electrophoretic mobility shift assays show, that an intestinal nuclear factor (NF-LPH1) binds to a sequence (-40 to -54) located close to the TATA-box. Enterocytes from newborn pigs with high lactase activity contain high amounts of NF-LPH1, whereas enterocytes from adult pigs with low lactase activity contain low amounts of NF-LPH1. The liver does not contain lactase activity, and NF-LPH1 is not present in liver nuclear extracts in detectable amounts. This indicates that NF-LPH1 is involved in the decline of lactase at weaning and may be of importance for the molecular explanation of hypolactasia in humans. It was demonstrated by transfection of two different promoter-reporter gene constructs into Caco2 cells, that there are additional cis-element(s) in the region -142 to approximately -980, which are important for the transcription of the lactase-phlorizin hydrolase gene.
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PMID:A novel intestinal trans-factor (NF-LPH1) interacts with the lactase-phlorizin hydrolase promoter and co-varies with the enzymatic activity. 140 Mar 59

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.
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PMID:Regulation of the expression of carbohydrate digestion/absorption-related genes. 1124 78

It has been previously demonstrated that the expression of lactase-phlorizin hydrolase (LPH) and sucrase-isomaltase (SI) genes are higher in rats fed a high-carbohydrate/low-fat (HCT) diet than in those fed a low-carbohydrate/high-fat (LCT) diet. In the present study, using a nuclear run-on assay we clearly show that higher expression of LPH and SI genes in jejunum of rats fed the HCT diet compared with those fed a LCT diet was regulated at the transcription levels. DNase I foot printing analysis of the 5' flanking region of the rat LPH gene demonstrated that by incubating the jejunal nuclear extract the protected region was conserved as the same sequence as the homeodomain protein-binding element designated as CE-LPH1. UV-cross linking and electromobility shift assay in vitro clearly showed that Cdx-2 was including proteins bound to CE-LPH1. Moreover, in vitro binding of Cdx-2 to CE-LPH1 as well as SIF1, a cis-element identified as the binding element of Cdx-2 on the SI gene, in jejunal nuclear extracts of rats fed a HCT diet were greater than those fed a LCT diet. These results suggest that in vitro binding of Cdx-2 to CE-LPH1 as well as SIF1 in jejunal nuclear extracts is associated with the higher expression of the LPH and SI genes in rats fed the HCT diet compared with those fed a LCT diet.
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PMID:Higher expression of jejunal LPH gene in rats fed the high-carbohydrate/low-fat diet compared with those fed the low-carbohydrate/high-fat diet is associated with in vitro binding of Cdx-2 in nuclear proteins to its promoter regions. 1857 6