The Aryl Hydrocarbon Receptor: A Key Bridging Molecule of External and Internal Chemical Signals.
The Aryl Hydrocarbon Receptor: A Key Bridging Molecule of External and Internal Chemical Signals.
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DOI：
10.1021/acs.est.5b00385
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发表时间：
2015-08-18
影响因子：
11.4
通讯作者：
Zhao B
中科院分区：
文献类型：
--
作者：
Tian J;Feng Y;Fu H;Xie HQ;Jiang JX;Zhao B
芳烃受体（AhR）是一种高度进化保守的配体激活转录因子，以介导二恶英和二恶英样化合物的毒性而闻名。AhR缺失小鼠的表型，以及最近发现的各种内源性和植物来源的配体，表明AhR除了在感知环境化学物质方面的作用外，还在正常细胞生理中发挥着不可或缺的作用。在这里，我们总结了目前关于AhR信号通路、其配体和AhR介导的细胞特化、宿主防御和解毒作用的知识。ahr介导的健康影响，特别是在肝脏，免疫和神经系统，以及在肿瘤发生的讨论。本文综述了二恶英对鱼类和鸟类的胚胎毒性和免疫抑制作用。最近的数据表明，AhR是多种信号通路的交汇点，这些信号通路告知细胞其外部和内部环境。因此，通过AhR配体介导的干预和其他AhR信号的扰动，AhR通路是治疗神经、肝脏和自身免疫性疾病的一个有希望的潜在靶点。此外，利用在动物模型上获得的现有实验室数据，以ahr为中心的不良后果途径分析有助于重新检查特定或混合化合物对野生动物的已知和潜在不良后果。
The aryl hydrocarbon receptor (AhR) is a highly evolutionary conserved, ligand-activated transcription factor that is best known to mediate the toxicities of dioxins and dioxin-like compounds. Phenotype of AhR-null mice, together with the recent discovery of a variety of endogenous and plant-derived ligands, point to the integral roles of AhR in normal cell physiology, in addition to its roles in sensing the environmental chemicals. Here, we summarize the current knowledge about AhR signaling pathways, its ligands and AhR-mediated effects on cell specialization, host defense and detoxification. AhR-mediated health effects particularly in liver, immune, and nervous systems, as well as in tumorgenesis are discussed. Dioxin-initiated embryotoxicity and immunosuppressive effects in fish and birds are reviewed. Recent data demonstrate that AhR is a convergence point of multiple signaling pathways that inform the cell of its external and internal environments. As such, AhR pathway is a promising potential target for therapeutics targeting nervous, liver, and autoimmune diseases through AhR ligand-mediated interventions and other perturbations of AhR signaling. Additionally, using available laboratory data obtained on animal models, AhR-centered adverse outcome pathway analysis is useful in reexamining known and potential adverse outcomes of specific or mixed compounds on wildlife.