PMID- 37078133 OWN - NLM STAT- MEDLINE DCOM- 20230918 LR - 20230920 IS - 1099-1263 (Electronic) IS - 0260-437X (Linking) VI - 43 IP - 10 DP - 2023 Oct TI - Development of a yeast reporter gene assay to detect ligands of freshwater cladoceran Daphnia magna ultraspiracle, a homolog of vertebrate retinoid X receptors. PG - 1447-1461 LID - 10.1002/jat.4476 [doi] AB - Endocrine-disrupting chemicals (EDCs) often affect homeostatic regulation in living organisms by directly acting on nuclear receptors (NRs). Retinoid X receptors (RXRs), the most highly conserved members of the NR superfamily during evolution, function as partners to form heterodimers with other NRs, such as retinoic acid, thyroid hormone, and vitamin D(3) receptors. RXRs also homodimerize and induce the expression of target genes upon binding with their natural ligand, 9-cis-retinoic acid (9cRA), and typical EDCs organotin compounds, such as tributyltin and triphenyltin. In the present study, we established a new yeast reporter gene assay (RGA) to detect the ligands of freshwater cladoceran Daphnia magna ultraspiracle (Dapma-USP), a homolog of vertebrate RXRs. D. magna has been used as a representative crustacean species for aquatic EDC assessments in the Organization for Economic Corporation and Development test guidelines. Dapma-USP was expressed along with the Drosophila melanogaster steroid receptor coactivator Taiman in yeast cells carrying the lacZ reporter plasmid. The RGA for detecting agonist activity of organotins and o-butylphenol was improved by use of mutant yeast strains lacking genes encoding cell wall mannoproteins and/or plasma membrane drug efflux pumps as hosts. We also showed that a number of other human RXR ligands, phenol and bisphenol A derivatives, and terpenoid compounds such as 9c-RA exhibited antagonist activity on Dapma-USP. Our newly established yeast-based RGA system is valuable as the first screening tool to detect ligand substances for Dapma-USP and for evaluating the evolutionary divergence of the ligand responses of RXR homologs between humans and D. magna. CI - (c) 2023 John Wiley & Sons Ltd. FAU - Ito-Harashima, Sayoko AU - Ito-Harashima S AD - Department of Biological Science, Graduate School of Science, Osaka Prefecture University, Sakai, Japan. AD - Department of Applied Biological Chemistry, Graduate School of Agriculture, Osaka Metropolitan University, Sakai, Japan. FAU - Tsubouchi, Yumiko AU - Tsubouchi Y AD - Department of Biological Science, Graduate School of Science, Osaka Prefecture University, Sakai, Japan. FAU - Takada, Eiji AU - Takada E AD - Department of Biological Science, Graduate School of Science, Osaka Prefecture University, Sakai, Japan. FAU - Kawanishi, Masanobu AU - Kawanishi M AD - Department of Biological Science, Graduate School of Science, Osaka Prefecture University, Sakai, Japan. AD - Department of Biological Chemistry, Graduate School of Science, Osaka Metropolitan University, Sakai, Japan. FAU - Yagi, Takashi AU - Yagi T AUID- ORCID: 0000-0002-5476-8424 AD - Department of Biological Science, Graduate School of Science, Osaka Prefecture University, Sakai, Japan. AD - Department of Biological Chemistry, Graduate School of Science, Osaka Metropolitan University, Sakai, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230504 PL - England TA - J Appl Toxicol JT - Journal of applied toxicology : JAT JID - 8109495 RN - 0 (Retinoid X Receptors) RN - 0 (Ligands) RN - 53282-60-3 (4-dansyl aminophenylmercuric acetate) SB - IM MH - Animals MH - Humans MH - Retinoid X Receptors/genetics/metabolism MH - Ligands MH - *Saccharomyces cerevisiae/genetics/metabolism MH - Genes, Reporter MH - *Daphnia/genetics/metabolism MH - Drosophila melanogaster/genetics MH - Vertebrates/genetics/metabolism OTO - NOTNLM OT - Daphnia magna OT - organotin OT - retinoid X receptor OT - ultraspiracle OT - yeast reporter gene assay EDAT- 2023/04/20 06:42 MHDA- 2023/09/18 12:44 CRDT- 2023/04/20 03:03 PHST- 2023/04/16 00:00 [revised] PHST- 2022/10/01 00:00 [received] PHST- 2023/04/17 00:00 [accepted] PHST- 2023/09/18 12:44 [medline] PHST- 2023/04/20 06:42 [pubmed] PHST- 2023/04/20 03:03 [entrez] AID - 10.1002/jat.4476 [doi] PST - ppublish SO - J Appl Toxicol. 2023 Oct;43(10):1447-1461. doi: 10.1002/jat.4476. Epub 2023 May 4.