Induction of AHR Signaling in Response to the Indolimine Class of Microbial Stress Metabolites.
Induction of AHR Signaling in Response to the Indolimine Class of Microbial Stress Metabolites.
复制标题
DOI：
10.3390/metabo13090985
复制
发表时间：
2023-08-31
期刊：
影响因子：
4.1
通讯作者：
Perdew GH
中科院分区：
文献类型：
--
作者：
Patel D;Murray IA;Dong F;Annalora AJ;Gowda K;Coslo DM;Krzeminski J;Koo I;Hao F;Amin SG;Marcus CB;Patterson AD;Perdew GH
芳香烃受体（aryl hydrocarbon receptor，AHR）是一种配体激活的转录因子，在胃肠道屏障功能、肿瘤发生中起重要作用，是一种新兴的药物靶点。常驻微生物群能够将色氨酸代谢成作为AHR配体的代谢物（例如，吲哚-3-乙酸酯）。最近，一组新的诱变色氨酸代谢产物命名为吲哚亚胺已被确定，产生的M。胃肠道中的摩根氏菌。在这里，我们确定，indolimine-200，-214，和-248是直接的AHR配体，可以诱导Cyp 1a 1转录和随后的CYP 1A 1酶活性，能够代谢致癌物苯并（a）芘的微粒体测定。此外，吲哚亚胺与细胞因子治疗组合增强结肠肿瘤细胞系中的IL 6表达。诱导AHR转录活性的indolimine-248的浓度未能增加DNA损伤。这些观察结果揭示了吲哚亚胺如何改变结肠肿瘤发生的另一个方面，超出了诱变活性。
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that plays an important role in gastrointestinal barrier function, tumorigenesis, and is an emerging drug target. The resident microbiota is capable of metabolizing tryptophan to metabolites that are AHR ligands (e.g., indole-3-acetate). Recently, a novel set of mutagenic tryptophan metabolites named indolimines have been identified that are produced by M. morganii in the gastrointestinal tract. Here, we determined that indolimine-200, -214, and -248 are direct AHR ligands that can induce Cyp1a1 transcription and subsequent CYP1A1 enzymatic activity capable of metabolizing the carcinogen benzo(a)pyrene in microsomal assays. In addition, indolimines enhance IL6 expression in a colonic tumor cell line in combination with cytokine treatment. The concentration of indolimine-248 that induces AHR transcriptional activity failed to increase DNA damage. These observations reveal an additional aspect of how indolimines may alter colonic tumorigenesis beyond mutagenic activity.
登录
查看更多内容
影响因子：
16.6
作者：
Gruszczyk, Jakub;Grandvuillemin, Loic;Lai-Kee-Him, Josephine;Paloni, Matteo;Savva, Christos G.;Germain, Pierre;Grimaldi, Marina;Boulahtouf, Abdelhay;Kwong, Hok-Sau;Bous, Julien;Ancelin, Aurelie;Bechara, Cherine;Barducci, Alessandro;Balaguer, Patrick;Bourguet, William
通讯作者：
Bourguet, William
影响因子：
3.4
作者：
Chen, Xufeng;Wong, Patty;Wong, Jeffrey Y. C.
通讯作者：
Wong, Jeffrey Y. C.
影响因子：
3
作者：
Morris, Garrett M.;Huey, Ruth;Lindstrom, William;Sanner, Michel F.;Belew, Richard K.;Goodsell, David S.;Olson, Arthur J.
通讯作者：
Olson, Arthur J.
影响因子：
4.6
作者：
John, Kaarthik;Lahoti, Tejas S.;Wagner, Kelly;Hughes, Jarod M.;Perdew, Gary H.
通讯作者：
Perdew, Gary H.
影响因子：
5.2
作者：
Huang Z;Schoones T;Wells JM;Fogliano V;Capuano E
通讯作者：
Capuano E