Cholesterol dependent downregulation of mouse and human apical sodium dependent bile acid transporter (ASBT) gene expression: molecular mechanism and physiological consequences

Thomas, C.; Landrier, J.-F.; Gaillard, D.; Grober, J.; Monnot, M.-C.; Athias, A.; Besnard, P.
September 2006
Gut;Sep2006, Vol. 55 Issue 9, p1321
Academic Journal
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 [³H]-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.


Related Articles

  • Murine Pancreatic Adenocarcinoma Reduces Ikaros Expression and Disrupts T Cell Homeostasis. Nelson, Nadine; Xiang, Shengyan; Zhang, Xiaohong; Gilvary, Danielle; Djeu, Julie; Husain, Kazim; Malafa, Mokenge; Vohra, Nasreen; Pilon-Thomas, Shari; Ghansah, Tomar // PLoS ONE;Jan2015, Vol. 10 Issue 1, p1 

    Background: Maintenance of T cell immune homeostasis is critical for adequate anti-tumor immunity. The transcription factor Ikaros is essential for lymphocyte development including T cells. Alterations in Ikaros expression occur in blood malignancies in humans and mice. In this study, we...

  • Rapid and reliable detection of CD44 variants in gastric carcinoma using a nested reverse transcription-polymerase chain reaction. YAN WANG; YUHONG LIU; BAI XIAO // Oncology Letters;Nov2015, Vol. 10 Issue 5, p2962 

    The present study aimed to establish a rapid and reliable method for detecting the expression of cluster of differentiation 44 variant (CD44v) in gastric carcinoma, and to investigate the significance of CD44v in gastric carcinoma. Using a nested reverse transcription-polymerase chain reaction...

  • Effects of Expression of Transcriptional Factor AP-1 FOSL1 Gene on Psoriatic Process. Sobolev, V. V.; Zolotorenko, A. D.; Soboleva, A. G.; Elkin, A. M.; Il'ina, S. A.; Serov, D. N.; Potekaev, N. N.; Tkachenko, S. B.; Minnibaev, M. T.; Piruzyan, A. L. // Bulletin of Experimental Biology & Medicine;Mar2011, Vol. 150 Issue 5, p632 

    We performed quantitative analysis of FOSL1 gene expression in lesional psoriatic skin. The expression of this gene in lesional psoriatic skin was significantly increased compared to that in unaffected areas. Enhanced FOSL1 expression significantly correlated with high psoriasis area and...

  • Expression Analysis of an R3-Type MYB Transcription Factor CPC-LIKE MYB4 (TRICHOMELESS2) and CPL4-Related Transcripts in Arabidopsis. Tominaga-Wada, Rumi; Nukumizu, Yuka // International Journal of Molecular Sciences;Mar2012, Vol. 13 Issue 3, p3478 

    The CAPRICE (CPC)-like MYB gene family encodes R3-type MYB transcription factors in Arabidopsis. There are six additional CPC-like MYB sequences in the Arabidopsis genome, including TRYPTICHON (TRY), ENHANCER OF TRY AND CPC1 and 2 (ETC1 and ETC2), ENHANCER OF TRY AND CPC3/CPC-LIKE MYB3...

  • Comparative analysis of sphingomyelin synthase 1 gene expression at the transcriptional and translational levels in human tissues. Limborska, Svetlana; Dergunova, Lyudmila; Sudarkina, Olga; Filippenkov, Ivan; Brodsky, Ilya // Molecular & Cellular Biochemistry;Aug2015, Vol. 406 Issue 1/2, p91 

    Sphingomyelin synthase 1 (SMS1) catalyses the biosynthesis of sphingomyelin in eukaryotic cells. We have previously determined the structure of the SGMS1 gene encoding this enzyme and a number of its alternative transcripts. Here, we describe a study of the expression of the full-length SMS1...

  • Low expression of T-cell transcription factor BCL11b predicts inferior survival in adult standard risk T-cell acute lymphoblastic leukemia patients. Bartram, Isabelle; Goekbuget, Nicola; Schlee, Cornelia; Heesch, Sandra; Fransecky, Lars; Schwartz, Stefan; Stuhlmann, Reingard; Schäfer-Eckhart, Kerstin; Starck, Michael; Reichle, Albrecht; Hoelzer, Dieter; Baldus, Claudia D.; Neumann, Martin // Journal of Hematology & Oncology;2014, Vol. 7 Issue 1, p1 

    Background Risk stratification, detection of minimal residual disease (MRD), and implementation of novel therapeutic agents have improved outcome in acute lymphoblastic leukemia (ALL), but survival of adult patients with T-cell acute lymphoblastic leukemia (T-ALL) remains unsatisfactory. Thus,...

  • 28-Homobrassinolide: a novel oxysterol transactivating LXR gene expression. Premalatha, R.; Srikumar, K.; Vijayalaksmi, D.; Kumar, G.; Mathur, P. // Molecular Biology Reports;Nov2014, Vol. 41 Issue 11, p7447 

    Cholesterol is the template for steroid hormone biosynthesis. Cholesterol homeostasis is regulated by Cyt-P oxygenated cholesterols acting as ligands on LXR-α and LXR-β transcription factors that are now emerging as drug targets. Heterodimerization of LXRs with retinoic acid receptor is...

  • Isolation and Characterization of Testis-Specific DMRT1 in the Tropical Abalone ( Haliotis asinina). Klinbunga, Sirawut; Amparyup, Piti; Khamnamtong, Bavornlak; Hirono, Ikuo; Aoki, Takashi; Jarayabhand, Padermsak // Biochemical Genetics;Feb2009, Vol. 47 Issue 1-2, p66 

    The Doublesex Male abnormal-3 Related Transcription factor-1 ( DMRT1) gene encodes a protein containing the DNA-binding motif called the DM domain, involved in the sexual development of various species. To gain insight into its implications for gonadal differentiation in the tropical abalone (...

  • Competitive priming PCR: a versatile method to generate cohesive terminus. Jin-Shui Pan; Zhi-Ping Zhang; Jia-Yan Cai; Jing Dong; Jian-Lin Ren; Xiao-Zhong Wang // Molecular Biology Reports;Mar2010, Vol. 37 Issue 3, p1421 

    Abstract  In the post-genomic era, providing a detailed description of protein functions poses a formidable challenge. To gain functional insights, we have to construct many kinds of expression vectors. DNA recombination based on polymerase chain reaction (PCR) and digestion followed by...


Read the Article


Sign out of this library

Other Topics