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芳香烃受体生物学的分子基础简介。

An introduction to the molecular basics of aryl hydrocarbon receptor biology.

机构信息

Institut für Umweltmedizinische Forschung (IUF) an der Heinrich-Heine-Universität Düsseldorf gGmbH, Auf'm Hennekamp 50, Düsseldorf, Germany.

出版信息

Biol Chem. 2010 Nov;391(11):1235-48. doi: 10.1515/BC.2010.128.

Abstract

Depending on their chemical structure and properties, environmental chemicals and other xenobiotics that enter the cell can affect cellular function by either nonselective binding to cellular macromolecules or by interference with cellular receptors, which would initiate a more defined cell biological response. One of these intracellular chemosensor molecules is the aryl hydrocarbon receptor (AhR), a transcription factor of the bHLH/PAS family that is known to mediate the biochemical and toxic effects of dioxins, polyaromatic hydrocarbons and related compounds. Numerous investigations have revealed that the AhR is not only a master regulator of drug metabolism activated by anthropogenic chemicals, but is also triggered by natural and endogenous ligands and can influence cell biological endpoints such as growth and differentiation. Cutting-edge research has identified new intriguing functions of the AhR, such as during proteasomal degradation of steroid hormone receptors, the cellular UVB stress response and the differentiation of certain T-cell subsets. In this review we provide both a survey of the fundamental basics of AhR biology and an insight into new functional aspects of AhR signaling to further stimulate research on this intriguing transcription factor at the interface between toxicology, cell biology and immunology.

摘要

根据其化学结构和特性,进入细胞的环境化学物质和其他外源性物质可以通过非选择性结合细胞大分子或干扰细胞受体来影响细胞功能,从而引发更明确的细胞生物学反应。这些细胞内化学感应器分子之一是芳香烃受体 (AhR),它是 bHLH/PAS 家族的转录因子,已知介导二恶英、多环芳烃和相关化合物的生化和毒性作用。大量研究表明,AhR 不仅是受人为化学物质激活的药物代谢的主要调节剂,而且还被天然和内源性配体触发,并能影响细胞生物学终点,如生长和分化。前沿研究确定了 AhR 的新的有趣功能,例如在甾体激素受体的蛋白酶体降解、细胞 UVB 应激反应和某些 T 细胞亚群的分化过程中。在这篇综述中,我们提供了 AhR 生物学的基本基础的概述,并深入了解 AhR 信号的新功能方面,以进一步激发在毒理学、细胞生物学和免疫学之间的界面上对这个有趣的转录因子的研究。

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