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芳烃受体调节剂的鉴定及转录组和代谢性芳烃受体-1谱的特征分析

Identification of Modulators of the Aryl Hydrocarbon Receptor and Characterization of Transcriptomic and Metabolic AhR-1 Profiles.

作者信息

Larigot Lucie, Bui Linh-Chi, de Bouvier Marine, Pierre Ophélie, Pinon Grégory, Fiocca Justine, Ozeir Mohammad, Tourette Cendrine, Ottolenghi Chris, Imbeaud Sandrine, Pontoizeau Clément, Blaise Benjamin J, Chevallier Aline, Tomkiewicz Céline, Legrand Béatrice, Elena-Herrmann Bénédicte, Néri Christian, Brinkmann Vanessa, Nioche Pierre, Barouki Robert, Ventura Natascia, Dairou Julien, Coumoul Xavier

机构信息

INSERM UMR-S1124, T3S, Toxicologie Environnementale, Cibles Thérapeutiques, Signalisation Cellulaire et Biomarqueurs, Université Paris Cité, 75006 Paris, France.

CNRS UMR 8601, Metabolism, Pharmacochemistry and Neurochemistry, Université Paris Cité, 75006 Paris, France.

出版信息

Antioxidants (Basel). 2022 May 23;11(5):1030. doi: 10.3390/antiox11051030.

Abstract

The Aryl hydrocarbon Receptor (AhR) is a xenobiotic sensor in vertebrates, regulating the metabolism of its own ligands. However, no ligand has been identified to date for any AhR in invertebrates. In  , the AhR ortholog, AHR-1, displays physiological functions. Therefore, we compared the transcriptomic and metabolic profiles of worms expressing AHR-1 or not and investigated the putative panel of chemical AHR-1 modulators. The metabolomic profiling indicated a role for AHR-1 in amino acids, carbohydrates, and fatty acids metabolism. The transcriptional profiling in neurons expressing AHR-1, identified 95 down-regulated genes and 76 up-regulated genes associated with neuronal and metabolic functions in the nervous system. A gene reporter system allowed us to identify several AHR-1 modulators including bacterial, dietary, or environmental compounds. These results shed new light on the biological functions of AHR-1 in   and perspectives on the evolution of the AhR functions across species.

摘要

芳烃受体(AhR)是脊椎动物中的一种外源性物质传感器,可调节其自身配体的代谢。然而,迄今为止尚未在无脊椎动物中鉴定出任何AhR的配体。在秀丽隐杆线虫中,AhR直系同源物AHR-1具有生理功能。因此,我们比较了表达AHR-1和不表达AHR-1的线虫的转录组和代谢谱,并研究了潜在的化学AHR-1调节剂。代谢组学分析表明AHR-1在氨基酸、碳水化合物和脂肪酸代谢中发挥作用。在表达AHR-1的神经元中的转录组分析,鉴定出95个下调基因和76个上调基因,这些基因与神经系统中的神经元和代谢功能相关。基因报告系统使我们能够鉴定出几种AHR-1调节剂,包括细菌、饮食或环境化合物。这些结果为AHR-1在秀丽隐杆线虫中的生物学功能以及AhR功能跨物种进化的前景提供了新的线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8dd9/9137885/e6d0d806971f/antioxidants-11-01030-g001.jpg

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