Towards molecular understanding of species differences in dioxin sensitivity: initial characterization of Ah receptor cDNAs in birds and an amphibian.
Towards molecular understanding of species differences in dioxin sensitivity: initial characterization of Ah receptor cDNAs in birds and an amphibian.
复制标题
对二恶英敏感性物种差异的分子理解：鸟类和两栖动物中 Ah 受体 cDNA 的初步表征。
DOI：
10.1016/s0141-1136(00)00045-3
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发表时间：
2000
影响因子：
3.3
通讯作者：
Hahn,ME
中科院分区：
文献类型：
--
作者：
Karchner,SI;Kennedy,SW;Trudeau,S;Hahn,ME
2，3，7，8-四氯二苯并-对-二恶英（TCDD）和相关的平面卤代芳烃（PHAH）对大多数脊椎动物具有高毒性，但在脊椎动物类内和类间的敏感性存在显着的物种差异。例如，在培养的禽类肝细胞中的研究已经揭示了禽类对PHAH的不同敏感性[Kennedy et al.（1996）.毒理学.应用药理学，141，214-230]。芳香烃受体（AHR）的特征或表达的差异可能导致这些物种在PHAH反应性方面的差异。为了研究不同PHAH敏感性的分子机制，我们已经开始表征白色来航鸡（原鸡），北京鸭（鸭），和普通燕鸥（燕鸥），以及两栖动物，泥小狗（斑节）的AHR。克隆并测序了包含螺旋-环-螺旋和PAS结构域的部分AHR cDNA。该区域的氨基酸序列比较表明，鸟类物种之间的高度序列保守性（97%的氨基酸同一性）。鸟类序列与小鼠或mudpuppy之间的同一性百分比较低（79%）; mudpuppy AHR与小鼠AHR的同一性为74%。这些和其他AHR氨基酸序列的系统发育分析表明，鸟类和泥狗AHR更密切相关的哺乳动物和鱼类AHR 1的形式比鱼类AHR 2。未来的研究包括这些和其他非哺乳动物脊椎动物AHR的体外表达和功能表征。
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related planar halogenated aromatic hydrocarbons (PHAHs) are highly toxic to most vertebrate animals, but there are dramatic species differences in sensitivity, both within and among vertebrate classes. For example, studies in cultured avian hepatocytes have revealed differential sensitivity of birds to PHAHs [Kennedy et al. (1996). Toxicol. Appl. Pharmacol., 141, 214–230]. Differences in the characteristics or expression of the aryl hydrocarbon receptor (AHR) could contribute to these species differences in PHAH responsiveness. To investigate the molecular mechanism of differential PHAH sensitivity, we have begun to characterize the AHR in white leghorn chicken (Gallus gallus), Pekin duck (Anas platyrhynchos), and common tern (Sterna hirundo), as well as an amphibian, mudpuppy (Necturus maculosus). Partial AHR cDNAs encompassing the helix-loop-helix and PAS domains were cloned and sequenced. Comparison of amino acid sequences in this region indicated a high degree of sequence conservation among the bird species (97% amino acid identity). The percent identity between bird sequences and either mouse or mudpuppy was lower (79%); the mudpuppy AHR was 74% identical to the mouse AHR. Phylogenetic analysis of these and other AHR amino acid sequences showed that the bird and mudpuppy AHRs were more closely related to mammalian and fish AHR1 forms than to fish AHR2. Future studies include the in vitro expression and functional characterization of AHRs from these and other non-mammalian vertebrates.