Evolution of the pregnane x receptor: adaptation to cross-species differences in biliary bile salts

Matthew D Krasowski; Kazuto Yasuda; Lee R Hagey; Erin G Schuetz

doi:10.1210/me.2004-0427

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Evolution of the pregnane x receptor: adaptation to cross-species differences in biliary bile salts

Journal article

Open access

Peer reviewed

Evolution of the pregnane x receptor: adaptation to cross-species differences in biliary bile salts

Matthew D Krasowski, Kazuto Yasuda, Lee R Hagey and Erin G Schuetz

Molecular endocrinology (Baltimore, Md.), Vol.19(7), pp.1720-1739

07/2005

DOI: 10.1210/me.2004-0427

PMCID: PMC2238640

PMID: 15718292

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Abstract

The pregnane X receptor (PXR) regulates the metabolism and elimination of bile salts, steroids, and xenobiotics. The sequence of the PXR ligand-binding domain diverges extensively between different animals, suggesting interspecies differences in ligands. Of the endogenous ligands known to activate PXR, biliary bile salts vary the most across vertebrate species, ranging from 27-carbon (C27) bile alcohol sulfates (early fish, amphibians) to C24 bile acids (birds, mammals). Using a luciferase-based reporter assay, human PXR was activated by a wide variety of bile salts. In contrast, zebrafish PXR was activated efficiently only by cyprinol sulfate, the major zebrafish bile salt, but not by recent bile acids. Chicken, mouse, rat, and rabbit PXRs were all activated by species-specific bile acids and by early fish bile alcohol sulfates. In addition, phylogenetic analysis using maximum likelihood demonstrated evidence for nonneutral evolution of the PXR ligand-binding domain. PXR activation by bile salts has expanded from narrow specificity for C27 bile alcohol sulfates (early fish) to a broader specificity for recent bile acids (birds, mammals). PXR specificity for bile salts has thus paralleled the increasing complexity of the bile salt synthetic pathway during vertebrate evolution, an unusual example of ligand-receptor coevolution in the nuclear hormone receptor superfamily.

Rabbits

Bile Acids and Salts - pharmacology

Xenopus Proteins - drug effects

Species Specificity

Receptors, Cytoplasmic and Nuclear - drug effects

Humans

Xenopus laevis

Bile Acids and Salts - chemistry

Rats

Zebrafish

Receptors, Cytoplasmic and Nuclear - agonists

Receptors, Cytoplasmic and Nuclear - genetics

Phylogeny

Receptors, Steroid - agonists

Receptors, Cytoplasmic and Nuclear - classification

Receptors, Steroid - classification

Cholestanols - pharmacology

Animals

Receptors, Steroid - genetics

Mice

Molecular Structure

Bile Acids and Salts - physiology

Evolution, Molecular

Details

Title: Subtitle: Evolution of the pregnane x receptor: adaptation to cross-species differences in biliary bile salts
Creators: Matthew D Krasowski - University of Pittsburgh, Department of Pathology, 200 Lothrop, Pittsburgh, PA 15213, USA. kra3@uchicago.edum
Kazuto Yasuda
Lee R Hagey
Erin G Schuetz
Resource Type: Journal article
Publication Details: Molecular endocrinology (Baltimore, Md.), Vol.19(7), pp.1720-1739
Publisher: United States
DOI: 10.1210/me.2004-0427
PMID: 15718292
PMCID: PMC2238640
ISSN: 0888-8809
eISSN: 1944-9917
Grant note: U01 GM061374 / NIGMS NIH HHS R01 GM060346-04 / NIGMS NIH HHS U01 GM61393 / NIGMS NIH HHS U01 GM61374 / NIGMS NIH HHS GM60346 / NIGMS NIH HHS U01 GM061393-060009 / NIGMS NIH HHS P30 CA21765 / NCI NIH HHS R01 GM060346 / NIGMS NIH HHS P30 CA021765 / NCI NIH HHS U01 GM061393 / NIGMS NIH HHS R01 GM060346-03 / NIGMS NIH HHS
Language: English
Date published: 07/2005
Academic Unit: Pathology
Record Identifier: 9984047680302771

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