Larigot Lucie, Juricek Ludmila, Dairou Julien, Coumoul Xavier
INSERM UMR-S 1124, Toxicologie Pharmacologie et Signalisation Cellulaire, 45 rue des Saints-Pères, 75006 Paris, France.
Université Paris Descartes, Sorbonne Paris Cité, 45 rue des Saints-Pères, 75006 Paris, France.
Biochim Open. 2018 Jun 11;7:1-9. doi: 10.1016/j.biopen.2018.05.001. eCollection 2018 Dec.
Animals and humans are exposed each day to a multitude of chemicals in the air, water and food. They have developed a battery of enzymes and transporters that facilitate the biotransformation and elimination of these compounds. Moreover, a majority of these enzymes and transporters are inducible due to the activation of xenobiotic receptors which act as transcription factors for the regulation of their target genes (such as xenobiotic metabolizing enzymes, see below §4 for the AhR). These receptors include several members of the nuclear/steroid receptor family (CAR for Constitutive Androstane Receptor, PXR for Pregnane X Receptor) but also the Aryl hydrocarbon Receptor or AhR, a member of the bHLH-PAS family (basic Helix-Loop-Helix - Period/ARNT/Single minded). In addition to the regulation of xenobiotic metabolism, numerous alternative functions have been characterized for the AhR since its discovery. These alternative functions will be described in this review along with its endogenous functions as revealed by experiments performed on knock-out animals.
动物和人类每天都会接触到空气、水和食物中的大量化学物质。它们已经形成了一系列酶和转运蛋白,以促进这些化合物的生物转化和消除。此外,由于外源性受体的激活,这些酶和转运蛋白中的大多数是可诱导的,外源性受体作为转录因子来调节其靶基因(如外源性代谢酶,关于芳烃受体(AhR)见下文第4节)。这些受体包括核/类固醇受体家族的几个成员(组成型雄甾烷受体CAR、孕烷X受体PXR),还有芳烃受体(AhR),它是bHLH-PAS家族(碱性螺旋-环-螺旋-周期/芳烃受体核转运蛋白/单一 minded)的成员。自发现以来,除了对外源性物质代谢的调节作用外,AhR还具有许多其他功能。本综述将描述这些其他功能以及通过对基因敲除动物进行实验所揭示的其内源性功能。