Cholesterol dependent downregulation of mouse and human apical sodium dependent bile acid transporter (ASBT) gene expression: molecular mechanism and physiological consequences
| Autor: | Marie-Claude Monnot, Jean-François Landrier, Jacques Grober, Charles Thomas, Philippe Besnard, Dany Gaillard, Anne Athias |
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| Přispěvatelé: | Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Centre des Sciences du Goût ( CSG ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Physiologie de la Nutrition, Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Laboratoire des Lipoprotéines humaines et interactions vasculaires, Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Rok vydání: | 2006 |
| Předmět: |
Male
Organic anion transporter 1 [SDV]Life Sciences [q-bio] Electrophoretic Mobility Shift Assay Intestinal absorption Cholesterol Dietary chemistry.chemical_compound Mice 0302 clinical medicine Gene expression Hepatocyte Nuclear Factor 1-alpha Promoter Regions Genetic Cells Cultured 0303 health sciences Bile acid Symporters Liver Disease digestive oral and skin physiology Gastroenterology Real-time polymerase chain reaction 030220 oncology & carcinogenesis [ SCCO.NEUR ] Cognitive science/Neuroscience Sterol Regulatory Element Binding Protein 2 medicine.medical_specialty medicine.drug_class Molecular Sequence Data Down-Regulation Organic Anion Transporters Sodium-Dependent Biology Transfection digestive system Bile Acids and Salts 03 medical and health sciences Organ Culture Techniques Ileum Internal medicine medicine Animals Humans RNA Messenger 030304 developmental biology Base Sequence Cholesterol [SCCO.NEUR]Cognitive science/Neuroscience Molecular biology Sterol Mice Inbred C57BL Endocrinology chemistry Intestinal Absorption biology.protein Mutagenesis Site-Directed Sterol regulatory element-binding protein 2 Caco-2 Cells [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition |
| Zdroj: | Gut Gut, BMJ Publishing Group, 2006, 55, pp.1321-1331. 〈10.1136/gut.2005.085555〉 Gut, BMJ Publishing Group, 2006, 55, pp.1321-1331. ⟨10.1136/gut.2005.085555⟩ |
| ISSN: | 0017-5749 |
| DOI: | 10.1136/gut.2005.085555〉 |
| Popis: | Background and aims: Faecal bile acid elimination greatly contributes to cholesterol homeostasis. Synthesised from cholesterol in the liver, bile acids are actively reclaimed in the ileum by the apical sodium dependent bile acid transporter (ASBT). Although the expression level of ASBT affects body cholesterol balance, the impact of cholesterol on ASBT gene expression remains unclear. In this study, the effect of cholesterol on ASBT expression and ileal bile acid uptake was explored in vivo and in vitro. Methods: ASBT gene expression was assessed by real time quantitative polymerase chain reaction and northern or western blotting, or both, in mice subjected to a 2% cholesterol diet for two weeks, in mouse ileal explants, or in human enterocyte-like Caco-2 cells cultured in sterol enriched or depleted media. Bile acid uptake was determined by measuring [ 3 H]-taurocholic acid influx into in situ isolated ileal loops from mice or into differentiated Caco-2 cells. Molecular analysis of mouse and human ASBT promoters was undertaken with reporter assays, site directed mutagenesis, and electrophoretic mobility shift assays. Results: In mice, cholesterol enriched diet triggered a downregulation of ASBT expression (mRNA and protein), a fall in ileal bile acid uptake, and a rise in the faecal excretion of bile acids. This effect was direct as it was reproduced ex vivo using mouse ileal explants and in vitro in differentiated Caco-2 cells. Conclusions: This regulation, which involves an original partnership between SREBP-2 and HNF-1α transcription factors, affects ileal bile acid recycling and thus might participate in the maintenance of body cholesterol homeostasis. |
| Databáze: | OpenAIRE |
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