Coordinate transcriptional regulation of bile acid homeostasis and drug metabolism - PubMed

Affiliations

• PMID: 15581596
• DOI: 10.1016/j.abb.2004.09.019

Review

Coordinate transcriptional regulation of bile acid homeostasis and drug metabolism

Jyrki J Eloranta et al. Arch Biochem Biophys. 2005.

Abstract

Drugs and bile acids are taken up into hepatocytes by specialized transport proteins localized at the basolateral membrane, e.g., organic anion transporting polypeptides . Following intracellular metabolism by cytochrome P450 (CYP) enzymes, drug metabolites are excreted into bile or urine via ATP-dependent multidrug resistance proteins (MDR1 and MRPs). Bile acids are excreted mainly via the bile salt export pump (BSEP, ABCB11). The genes coding for drug and bile acid transporters and CYP enzymes are regulated by a complex network of transcriptional cascades, notably by the ligand-activated nuclear receptors FXR, PXR, and CAR and by the ligand-independent nuclear receptor HNF-4alpha. The bile acid synthesizing enzymes CYP7A1, CYP8B1, and CYP27A1 are subject to negative feedback regulation by bile acids, which is partly mediated through the transcriptional repressor SHP. The role of transcriptional cofactors, such as SRC-1 and PGC-1, in mediating the gene-specific effects of individual nuclear receptors is becoming increasingly evident.

Similar articles

• Ligand-activated pregnane X receptor interferes with HNF-4 signaling by targeting a common coactivator PGC-1alpha. Functional implications in hepatic cholesterol and glucose metabolism.

  Bhalla S, Ozalp C, Fang S, Xiang L, Kemper JK. Bhalla S, et al. J Biol Chem. 2004 Oct 22;279(43):45139-47. doi: 10.1074/jbc.M405423200. Epub 2004 Aug 18. J Biol Chem. 2004. PMID: 15322103

• Disrupted coordinate regulation of farnesoid X receptor target genes in a patient with cerebrotendinous xanthomatosis.

  Honda A, Salen G, Matsuzaki Y, Batta AK, Xu G, Hirayama T, Tint GS, Doy M, Shefer S. Honda A, et al. J Lipid Res. 2005 Feb;46(2):287-96. doi: 10.1194/jlr.M400256-JLR200. Epub 2004 Dec 1. J Lipid Res. 2005. PMID: 15576845

• Coordinated induction of bile acid detoxification and alternative elimination in mice: role of FXR-regulated organic solute transporter-alpha/beta in the adaptive response to bile acids.

  Zollner G, Wagner M, Moustafa T, Fickert P, Silbert D, Gumhold J, Fuchsbichler A, Halilbasic E, Denk H, Marschall HU, Trauner M. Zollner G, et al. Am J Physiol Gastrointest Liver Physiol. 2006 May;290(5):G923-32. doi: 10.1152/ajpgi.00490.2005. Epub 2005 Dec 15. Am J Physiol Gastrointest Liver Physiol. 2006. PMID: 16357057

• Coordinate transcriptional regulation of transport and metabolism.

  Eloranta JJ, Meier PJ, Kullak-Ublick GA. Eloranta JJ, et al. Methods Enzymol. 2005;400:511-30. doi: 10.1016/S0076-6879(05)00028-5. Methods Enzymol. 2005. PMID: 16399367 Review.

• [Mechanisms of bile acid biosynthesis regulation--autoregulation by bile acids].

  Hebanowska A. Hebanowska A. Postepy Biochem. 2011;57(3):314-23. Postepy Biochem. 2011. PMID: 22235657 Review. Polish.

Cited by

• Current concepts of mechanisms in drug-induced hepatotoxicity.

  Russmann S, Kullak-Ublick GA, Grattagliano I. Russmann S, et al. Curr Med Chem. 2009;16(23):3041-53. doi: 10.2174/092986709788803097. Curr Med Chem. 2009. PMID: 19689281 Free PMC article. Review.

• Molecular mechanisms of cholestasis.

  Zollner G, Trauner M. Zollner G, et al. Wien Med Wochenschr. 2006 Jul;156(13-14):380-5. doi: 10.1007/s10354-006-0312-7. Wien Med Wochenschr. 2006. PMID: 16937039 Review.

• Hepatocyte-specific ablation of Foxa2 alters bile acid homeostasis and results in endoplasmic reticulum stress.

  Bochkis IM, Rubins NE, White P, Furth EE, Friedman JR, Kaestner KH. Bochkis IM, et al. Nat Med. 2008 Aug;14(8):828-36. doi: 10.1038/nm.1853. Epub 2008 Jul 27. Nat Med. 2008. PMID: 18660816 Free PMC article.

• Analysis of ileal sodium/bile acid cotransporter and related nuclear receptor genes in a family with multiple cases of idiopathic bile acid malabsorption.

  Montagnani M, Abrahamsson A, Gälman C, Eggertsen G, Marschall HU, Ravaioli E, Einarsson C, Dawson PA. Montagnani M, et al. World J Gastroenterol. 2006 Dec 21;12(47):7710-4. doi: 10.3748/wjg.v12.i47.7710. World J Gastroenterol. 2006. PMID: 17171805 Free PMC article.

• Function and pathophysiological importance of ABCB4 (MDR3 P-glycoprotein).

  Oude Elferink RP, Paulusma CC. Oude Elferink RP, et al. Pflugers Arch. 2007 Feb;453(5):601-10. doi: 10.1007/s00424-006-0062-9. Epub 2006 Apr 19. Pflugers Arch. 2007. PMID: 16622704 Review.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Other Literature Sources

  • The Lens - Patent Citations Database

• Medical

  • MedlinePlus Health Information

• Miscellaneous

  • NCI CPTAC Assay Portal