title: Potencies of red seabream AHR1- and AHR2-mediated transactivation by dioxins: implication of both AHRs in dioxin toxicity.
abstract: To evaluate species- and isoform-specific responses to dioxins and related compounds (DRCs) via aryl hydrocarbon receptor (AHR) in the red seabream ( Pagrus major ), we constructed a reporter gene assay system. Each expression plasmid of red seabream AHR1 (rsAHR1) and AHR2 (rsAHR2) together with a reporter plasmid containing red seabream CYP1A 5'-flanking region were transfected into COS-7 cells. The cells were treated with graded concentrations of seven DRC congeners including 2,3,7,8-TCDD, 1,2,3,7,8-PeCDD, 1,2,3,4,7,8-HxCDD, 2,3,7,8-TCDF, 2,3,4,7,8-PeCDF, 1,2,3,4,7,8-HxCDF, and PCB126. Both rsAHR1 and rsAHR2 exhibited dose-dependent responses for all the tested congeners. The rsAHR isoform-specific TCDD induction equivalency factors (rsAHR1- and rsAHR2-IEFs) were calculated on the basis of 2,3,7,8-TCDD relative potency derived from the dose-response of each congener. The rsAHR1-IEFs of PeCDD, HxCDD, TCDF, PeCDF, and HxCDF were estimated as 0.17, 0.29, 2.5, 1.5, and 0.27, respectively. For PCB126, no rsAHR1-IEF was given because of less than 10% 2,3,7,8-TCDD maximum response. The rsAHR2-IEFs of PeCDD, HxCDD, TCDF, PeCDF, HxCDF, and PCB126 were estimated as 0.38, 0.13, 1.5, 0.93, 0.20, and 0.0085, respectively. The rsAHR1/2-IEF profiles were different from WHO toxic equivalency factors for fish. In silico docking simulations supported that both rsAHRs have potentials to bind to these congeners. These results suggest that dioxin toxicities may be mediated by both rsAHRs in red seabreams.
authors: Department of Life and Nanopharmaceutical Science, Kyung Hee University, Hoegi Dong, Dongdaemun-Gu, Seoul 130-701, Korea.
authors: Su-Min
authors: SM
authors: Bak
authors: Midori
authors: M
authors: Iida
authors: Masashi
authors: M
authors: Hirano
authors: Hisato
authors: H
authors: Iwata
authors: Eun-Young
authors: EY
authors: Kim
mesh_terms: D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002522:Chlorocebus aethiops; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D004147:Dioxins / Q000378:metabolism / Q000633:toxicity*; D029941:Fish Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D017930:Genes, Reporter / Q000187:drug effects; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*; D021541:Sea Bream / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection; D014874:Water Pollutants, Chemical / Q000378:metabolism / Q000633:toxicity*; D015027:Zebrafish
chemical_list: D004147:Dioxins; D029941:Fish Proteins; D020033:Protein Isoforms; D018336:Receptors, Aryl Hydrocarbon; D014874:Water Pollutants, Chemical; D019363:Cytochrome P-450 CYP1A1