Hepatocyte nuclear factor-4alpha plays pivotal roles in the regulation of mouse carboxylesterase 2 gene transcription in mouse liver

Archives of Biochemistry and Biophysics
Tomomi FurihataKan Chiba

Abstract

The mouse carboxylesterase 2 isozyme, mCES2, is thought to play important roles in lipid metabolism and is expressed in the liver, kidney, and small intestine at high levels. In this study, we examined the molecular mechanisms controlling this tissue-specific expression of mCES2, and demonstrated that hepatocyte nuclear factor-4alpha (HNF-4alpha) could enhance transcription of the mCES2 gene in vitro and in vivo. It was found that effects of HNF-4alpha on the level of mCES2 promoter activity were repressed by small heterodimer partner (SHP) and chenodeoxycholic acid (CDCA) in luciferase assays. Accordingly, mCES2 gene transcription was repressed by CDCA treatment in mouse immortalized hepatocytes. Our results suggested that this repression resulted from the combined effects of both inhibition of HNF-4alpha transactivation ability by SHP and reduction of HNF-4alpha expression level. These findings show that HNF-4alpha plays an important role in the regulation of mCES2 gene transcription.

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Citations

Aug 31, 2010·DNA and Cell Biology·Alex K LeeSandra D O'Dell
Feb 19, 2010·Expert Opinion on Drug Metabolism & Toxicology·Jeff L StaudingerCurtis D Klaassen
Feb 18, 2010·Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics·Roger S HolmesJohn L Vandeberg
Feb 29, 2008·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Masakiyo Hosokawa
Mar 17, 2006·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Sachiyo KawashimaKan Chiba
Jan 26, 2016·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Yuanyuan LiYanqiao Zhang
Aug 22, 2006·Chemico-biological Interactions·Tetsuo Satoh, Masakiyo Hosokawa
Sep 4, 2009·Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics·Roger S HolmesJohn L Vandeberg

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