Development of yeast reporter assay for screening specific ligands of retinoic acid and retinoid X receptor subtypes
| Autor: | Shizuma Hirose, Kazuhiro Shiizaki, Tomoya Yoshikawa, Sayoko Ito-Harashima, Takashi Yagi, Masanobu Kawanishi, Eiji Takada |
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| Rok vydání: | 2014 |
| Předmět: |
Triphenyltin chloride
Receptors Retinoic Acid medicine.drug_class Saccharomyces cerevisiae Retinoic acid Tretinoin Biology Retinoid X receptor Ligands Toxicology chemistry.chemical_compound Genes Reporter medicine Humans Retinoid Receptor Pharmacology Reporter gene organic chemicals biology.organism_classification Yeast body regions Retinoid X Receptors chemistry Biochemistry embryonic structures |
| Zdroj: | Journal of Pharmacological and Toxicological Methods. 69:245-252 |
| ISSN: | 1056-8719 |
| Popis: | Introduction Retinoic acids are essential for embryonic development, tissue organization, and homeostasis and act via retinoic acid receptors (RARs) that form heterodimers with retinoid X receptors (RXRs). Human RARs and RXRs include the three subtypes α, β, and γ, which have varying distributions and physiological functions among human tissues. Recent reports show that subtype-specific binding of several chemicals to RARs or RXRs may lead to endocrine disruption. To evaluate these ligand-like chemicals, convenient assay systems for each receptor subtype are required. Methods We developed reporter assay yeasts to screen ligands for RXR subtype receptor homodimers. To screen RAR ligands, yeasts were engineered to express RAR subtypes with defective RXRα, which fails to bind to coactivators because of its shortened c-terminus. Results These assay yeasts were validated using known RXR- and RAR-specific ligands and subtype-specific responses were clearly shown. Subtype-specific ligand activities of the suspected chemical RAR or RXR ligands o - t -butylphenol, triphenyltin chloride, tributyltin chloride, and 4-nonylphenol were determined. Discussion The present assay yeasts may be valuable tools for subtype-specific assessments of unidentified environmental ligand chemicals and receptor-specific pharmaceuticals. |
| Databáze: | OpenAIRE |
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