An aryl hydrocarbon receptor repressor from Xenopus laevis: function, expression, and role in dioxin responsiveness during frog development.
An aryl hydrocarbon receptor repressor from Xenopus laevis: function, expression, and role in dioxin responsiveness during frog development.
复制标题
非洲爪蟾的芳基碳氢化合物受体阻遏物：功能、表达以及在青蛙发育过程中二恶英反应中的作用。
DOI：
10.1093/toxsci/kfn066
复制
发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Powell,WadeH
中科院分区：
文献类型：
--
作者：
Zimmermann,AnnaL;King,ElizabethA;Dengler,Emelyne;Scogin,ShanaR;Powell,WadeH
非洲爪蟾和其他蛙类对芳香烃受体（AHR）的异生素配体（包括2，3，7，8-四氯二苯并对二恶英（TCDD））的毒性极其不敏感。变质前的生命阶段是特别不敏感的，据报道，他们是难诱导的细胞色素P4501 As，这是很容易诱导老年动物。AHR阻遏物（AHR repressor，AHRR）是AHR基因家族的一员。AHRR的表达是由TCDD诱导的，然后在一个明显的负反馈回路中抑制AHR。在这项研究中，我们试图测试的假设，组成型AHRR表达的基础上缺乏TCDD的反应在青蛙的早期生命阶段。我们确定了编码85.3-kDa蛋白质的AHRR互补DNA的序列，该蛋白质与其他AHRR的bHLH/PAS结构域具有52-55%的同一性。在瞬时转染实验中，X. laevisAHRR抑制TCDD诱导的报告基因表达。LAEVISAHR partial，AHR 1 α或AHR 1 β。AHRR信使RNA在胚胎中以低水平表达（Nieuwkoop-Faber阶段33-38;约52 h.p.f.）在接触四氯二苯并对二恶英（42纳克/克湿重）后，其诱导作用大约增加两倍。相比之下，AHRR表现出较高的组成型表达，并诱导超过三倍，在蝌蚪在第52-55阶段（前变质;受精后104周），并在孤立的内脏阶段62蝌蚪（在变质顶极;受精后107周）。虽然诱导的幅度较小，但AHRR表达和诱导的时间模式与CYP 1A 6相似。因此，减弱了AHR靶基因的转录激活和低TCDD毒性。不能用AHRR的组成性高水平表达来解释光滑胚的形成。
Xenopus laevisand other frogs are extremely insensitive to the toxicity of xenobiotic ligands of the aryl hydrocarbon receptor (AHR), including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Premetamorphic life stages are especially insensitive, and they are reported to be refractory to induction of Cytochrome P4501As, which are readily induced in older animals. The AHR repressor (AHRR) is a member of the AHR gene family. AHRR expression is induced by TCDD; it then represses AHR in an apparent negative feedback loop. In this study, we sought to test the hypothesis that constitutive AHRR expression underlies the lack of TCDD responsiveness in frog early life stages. We determined the sequence of an AHRR complimentary DNA encoding an 85.3-kDa protein sharing 52–55% identity with the bHLH/PAS domains of other AHRRs. In transient transfection assays,X. laevisAHRR inhibited TCDD-induced reporter gene expression mediated by eitherX. laevisAHR paralog, AHR1α or AHR1β. AHRR messenger RNA was expressed at low levels in embryos (Nieuwkoop-Faber stage 33–38; approximately 52 h.p.f.) and was induced approximately twofold following TCDD exposure (42 ng/g wet weight). In contrast, AHRR exhibited higher constitutive expression and was induced more than threefold in tadpoles at stage 52–55 (prometamorphic; ∼4 weeks postfertilization) and in isolated viscera of stage 62 tadpoles (in the metamorphic climax; ∼7 weeks postfertilization). Although the magnitude of induction was smaller, the temporal pattern of AHRR expression and inducibility resembled that ofCYP1A6. Thus, attenuated transcriptional activation of AHR target genes and low TCDD toxicity inX. laevisembryos cannot be explained by constitutive, high-level expression of AHRR.