The zebrafish (Danio rerio) aryl hydrocarbon receptor type 1 is a novel vertebrate receptor
The zebrafish (Danio rerio) aryl hydrocarbon receptor type 1 is a novel vertebrate receptor
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DOI：
10.1124/mol.62.2.234
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发表时间：
2002-08-01
影响因子：
3.6
通讯作者：
Tanguay, RL
中科院分区：
文献类型：
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作者：
Andreasen, EA;Hahn, ME;Tanguay, RL
已知鱼类有两类不同的芳烃受体，它们在介导异生物质毒性中的作用尚不清楚。在这项研究中，我们已经确定和表征的cDNA暂时命名为斑马鱼AHR 1（zfAHR 1）。推导的氨基酸序列的分析表明，该蛋白质是不同的zfAHR 2和更密切相关的哺乳动物芳香烃受体（AHR）。zfAHR 1和zfAHR 2共有40%的氨基酸同一性，在N-末端一半共有58%。zfAHR 1基因定位于与含有人AHR的人7号染色体共享保守同线性的区域中的连锁群16，表明zfAHR 1是人AHR的直系同源物。zfAHR 2定位于单独的连锁群（LG 22）。两种zfAHR mRNA在早期发育中表达，但它们在成体组织中差异表达。zfAHR 2可以与zfARNT 2b二聚化，并特异性结合二恶英反应元件（DRE）。在相同的条件下，形成zfAHR 1/zfARNT 2b/DRE复合物;然而，相互作用相当弱。在表达zfARNT 2b和zfAHR 2的COS-7细胞中，2，3，7，8-四氯二苯并对二恶英（TCDD）暴露导致二恶英响应报告基因的显著诱导。在相同的实验中，TCDD暴露未能诱导zfAHR 1表达细胞中的报告基因。配体结合实验表明，差异zfAHR活动可归因于TCDD结合的差异，因为只有zfAHR 2表现出高亲和力结合[H-3] TCDD或β-萘酚酮。最后，使用嵌合zfAHR 1/zfAHR 2构建体，TCDD介导的转录活性的缺乏被定位于zfAHR 1的配体结合和C-末端结构域。
Fish are known to have two distinct classes of aryl hydrocarbon receptors, and their roles in mediating xenobiotic toxicity remain unclear. In this study, we have identified and characterized a cDNA tentatively named zebrafish AHR1 (zfAHR1). Analysis of the deduced amino acid sequence reveals that the protein is distinct from zfAHR2 and is more closely related to the mammalian aryl hydrocarbon receptor (AHR). zfAHR1 and zfAHR2 share 40% amino acid identity overall and 58% in the N-terminal half. The zfAHR1 gene maps to linkage group 16 in a region that shares conserved synteny with human chromosome 7 containing the human AHR, suggesting that the zfAHR1 is the ortholog of the human AHR. zfAHR2 maps to a separate linkage group (LG22). Both zfAHR mRNAs are expressed in early development, but they are differentially expressed in adult tissues. zfAHR2 can dimerize with zfARNT2b and binds with specificity to dioxin-responsive elements (DREs). Under identical conditions, zfAHR1/zfARNT2b/DRE complexes are formed; however, the interactions are considerably weaker. In COS-7 cells expressing zfARNT2b and zfAHR2, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure leads to a significant induction of dioxin-responsive reporter genes. In identical experiments, TCDD exposure fails to induce the reporter gene in zfAHR1-expressing cells. Ligand-binding experiments suggested that the differential zfAHR activities are attributable to differences in TCDD binding because only zfAHR2 exhibits high-affinity binding to [H-3] TCDD or beta-naphthoflavone. Finally, using chimeric zfAHR1/zfAHR2 constructs, the lack of TCDD-mediated transcriptional activity was localized to the ligand-binding and C-terminal domains of zfAHR1.