Dependence on the microtubule network and 90-kDa heat shock protein of phenobarbital-induced nuclear translocation of the rat constitutive androstane receptor

Molecular Pharmacology
Yuichiro KannoYoshio Inouye

Abstract

The role of the microtubule network in the constitutive androstane receptor (CAR)-mediated transactivation of CYP2B induced by phenobarbital (PB) in rat primary hepatocytes was investigated using the microtubule-disrupting agent nocodazole (NCZ). In human hepatocytes, it was reported that CAR mRNA expression was decreased by a microtubule-disrupting agent through the inhibition of glucocorticoid receptor (GR)-mediated transactivation. However, in the present study, we show that the rat CAR gene was unaffected by the GR-mediated pathway in rat primary hepatocytes treated with NCZ. The PB-induced expression of CYP2B mRNA was repressed in the presence of NCZ for 2 h before and during 4 h of PB treatment, whereas the CAR mRNA and protein expression levels were not affected. Furthermore, the transactivation of the PB-responsive enhancer module-luciferase reporter gene and the nuclear transport of CAR induced by PB were also repressed in the presence of NCZ. Based on these findings, microtubular integrity might be required for PB-induced nuclear translocation of CAR in rat primary hepatocytes. In the same procedures, except that NCZ was replaced with radicicol, the CYP2B mRNA expression induced by PB was also repressed. Taking these ...Continue Reading

References

Jan 9, 1999·The Journal of Biological Chemistry·R J HachéY A Lefebvre
Jan 16, 1999·Molecular and Cellular Biology·J G SavoryY A Lefebvre
Feb 26, 1999·The Journal of Biological Chemistry·T SueyoshiM Negishi
May 9, 2001·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·J SugataniT Sueyoshi
Jan 25, 2002·Annals of the New York Academy of Sciences·A K RoyB Chatterjee
Jul 20, 2002·Molecular Pharmacology·Bryan GoodwinChristopher Liddle
Aug 16, 2002·Molecular Pharmacology·Stephen S FergusonJoyce A Goldstein
May 26, 2004·Cellular Signalling·William B PrattDonald B DeFranco
Oct 16, 2004·The Journal of Biological Chemistry·Jennifer M HarrellWilliam B Pratt
Nov 8, 2005·Biological & Pharmaceutical Bulletin·Yuichiro KannoYoshio Inouye
May 10, 2007·Biochimica Et Biophysica Acta·Yuichiro KannoYoshio Inouye

❮ Previous
Next ❯

Citations

Feb 3, 2016·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Yoshio Inouye
Jan 7, 2014·Biochimica Et Biophysica Acta·Alejandra G ErlejmanMario D Galigniana
Dec 17, 2014·Acta Pharmacologica Sinica·Jiong YanWen Xie
Mar 5, 2011·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Yuichiro Kanno, Yoshio Inouye

❮ Previous
Next ❯

Related Concepts

Related Feeds

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Related Papers

Breast Cancer Research and Treatment
Heike Knüpfer, Rainer Preiss
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Hasan KorkayaMax S Wicha
© 2022 Meta ULC. All rights reserved