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Activation of Steroid and Xenobiotic Receptor (SXR, NR1I2) and Its Orthologs in Laboratory, Toxicologic, and Genome Model Species
BACKGROUND: Nuclear receptor subfamily 1, group I, member 2 (NR1I2), commonly known as steroid and xenobiotic receptor (SXR) in humans, is a key ligand-dependent transcription factor responsible for the regulation of xenobiotic, steroid, and bile acid metabolism. The ligand-binding domain is princip...
Autores principales: | , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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National Institute of Environmental Health Sciences
2008
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2453155/ https://www.ncbi.nlm.nih.gov/pubmed/18629309 http://dx.doi.org/10.1289/ehp.10853 |
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author | Milnes, Matthew R. Garcia, Adriana Grossman, Emily Grün, Felix Shiotsugu, Jason Tabb, Michelle M. Kawashima, Yukio Katsu, Yoshinao Watanabe, Hajime Iguchi, Taisen Blumberg, Bruce |
author_facet | Milnes, Matthew R. Garcia, Adriana Grossman, Emily Grün, Felix Shiotsugu, Jason Tabb, Michelle M. Kawashima, Yukio Katsu, Yoshinao Watanabe, Hajime Iguchi, Taisen Blumberg, Bruce |
author_sort | Milnes, Matthew R. |
collection | PubMed |
description | BACKGROUND: Nuclear receptor subfamily 1, group I, member 2 (NR1I2), commonly known as steroid and xenobiotic receptor (SXR) in humans, is a key ligand-dependent transcription factor responsible for the regulation of xenobiotic, steroid, and bile acid metabolism. The ligand-binding domain is principally responsible for species-specific activation of NR1I2 in response to xenobiotic exposure. OBJECTIVES: Our objective in this study was to create a common framework for screening NR1I2 orthologs from a variety of model species against environmentally relevant xenobiotics and to evaluate the results in light of using these species as predictors of xenobiotic disposition and for assessment of environmental health risk. METHODS: Sixteen chimeric fusion plasmid vectors expressing the Gal4 DNA-binding domain and species-specific NR1I2 ligand-binding domain were screened for activation against a spectrum of 27 xenobiotic compounds using a standardized cotransfection receptor activation assay. RESULTS: NR1I2 orthologs were activated by various ligands in a dose-dependent manner. Closely related species show broadly similar patterns of activation; however, considerable variation to individual compounds exists, even among species varying in only a few amino acid residues. CONCLUSIONS: Interspecies variation in NR1I2 activation by various ligands can be screened through the use of in vitro NR1I2 activation assays and should be taken into account when choosing appropriate animal models for assessing environmental health risk. |
format | Text |
id | pubmed-2453155 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | National Institute of Environmental Health Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-24531552008-07-14 Activation of Steroid and Xenobiotic Receptor (SXR, NR1I2) and Its Orthologs in Laboratory, Toxicologic, and Genome Model Species Milnes, Matthew R. Garcia, Adriana Grossman, Emily Grün, Felix Shiotsugu, Jason Tabb, Michelle M. Kawashima, Yukio Katsu, Yoshinao Watanabe, Hajime Iguchi, Taisen Blumberg, Bruce Environ Health Perspect Research BACKGROUND: Nuclear receptor subfamily 1, group I, member 2 (NR1I2), commonly known as steroid and xenobiotic receptor (SXR) in humans, is a key ligand-dependent transcription factor responsible for the regulation of xenobiotic, steroid, and bile acid metabolism. The ligand-binding domain is principally responsible for species-specific activation of NR1I2 in response to xenobiotic exposure. OBJECTIVES: Our objective in this study was to create a common framework for screening NR1I2 orthologs from a variety of model species against environmentally relevant xenobiotics and to evaluate the results in light of using these species as predictors of xenobiotic disposition and for assessment of environmental health risk. METHODS: Sixteen chimeric fusion plasmid vectors expressing the Gal4 DNA-binding domain and species-specific NR1I2 ligand-binding domain were screened for activation against a spectrum of 27 xenobiotic compounds using a standardized cotransfection receptor activation assay. RESULTS: NR1I2 orthologs were activated by various ligands in a dose-dependent manner. Closely related species show broadly similar patterns of activation; however, considerable variation to individual compounds exists, even among species varying in only a few amino acid residues. CONCLUSIONS: Interspecies variation in NR1I2 activation by various ligands can be screened through the use of in vitro NR1I2 activation assays and should be taken into account when choosing appropriate animal models for assessing environmental health risk. National Institute of Environmental Health Sciences 2008-07 2008-03-12 /pmc/articles/PMC2453155/ /pubmed/18629309 http://dx.doi.org/10.1289/ehp.10853 Text en http://creativecommons.org/publicdomain/mark/1.0/ Publication of EHP lies in the public domain and is therefore without copyright. All text from EHP may be reprinted freely. Use of materials published in EHP should be acknowledged (for example, ?Reproduced with permission from Environmental Health Perspectives?); pertinent reference information should be provided for the article from which the material was reproduced. Articles from EHP, especially the News section, may contain photographs or illustrations copyrighted by other commercial organizations or individuals that may not be used without obtaining prior approval from the holder of the copyright. |
spellingShingle | Research Milnes, Matthew R. Garcia, Adriana Grossman, Emily Grün, Felix Shiotsugu, Jason Tabb, Michelle M. Kawashima, Yukio Katsu, Yoshinao Watanabe, Hajime Iguchi, Taisen Blumberg, Bruce Activation of Steroid and Xenobiotic Receptor (SXR, NR1I2) and Its Orthologs in Laboratory, Toxicologic, and Genome Model Species |
title | Activation of Steroid and Xenobiotic Receptor (SXR, NR1I2) and Its Orthologs in Laboratory, Toxicologic, and Genome Model Species |
title_full | Activation of Steroid and Xenobiotic Receptor (SXR, NR1I2) and Its Orthologs in Laboratory, Toxicologic, and Genome Model Species |
title_fullStr | Activation of Steroid and Xenobiotic Receptor (SXR, NR1I2) and Its Orthologs in Laboratory, Toxicologic, and Genome Model Species |
title_full_unstemmed | Activation of Steroid and Xenobiotic Receptor (SXR, NR1I2) and Its Orthologs in Laboratory, Toxicologic, and Genome Model Species |
title_short | Activation of Steroid and Xenobiotic Receptor (SXR, NR1I2) and Its Orthologs in Laboratory, Toxicologic, and Genome Model Species |
title_sort | activation of steroid and xenobiotic receptor (sxr, nr1i2) and its orthologs in laboratory, toxicologic, and genome model species |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2453155/ https://www.ncbi.nlm.nih.gov/pubmed/18629309 http://dx.doi.org/10.1289/ehp.10853 |
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