期刊
JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS
卷 69, 期 3, 页码 245-252出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.vascn.2014.01.007
关键词
Saccharomyces cerevisiae; Retinoic acid receptor alpha,beta,gamma; Retinoid X receptor alpha,beta,gamma; Reporter assay; Endocrine disruptors
资金
- Industrial Technology Research Grant Program from the New Energy and Industrial Technology Development Organization (NEDO)
- Science and Technology Incubation Program in Advanced Regions from Japan Science and Technology Agency (JST)
- Japan Society for the Promotion of Science (JSPS) [24310047, 23590162]
- Grants-in-Aid for Scientific Research [23590162] Funding Source: KAKEN
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 alpha,beta and gamma, 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 RXRa, 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. (C) 2014 Elsevier Inc. All rights reserved.
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