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Aryl hydrocarbon receptor

Kateřina Lněničková, Lenka Skálová, Lucie Stuchlíková, Barbora Szotáková, Petra Matoušková
In the present study, time-dependency of the induction effect of a selective inducer on the activity, protein and mRNA levels of cytochromes P450 1A1/2 (CYP1A1/2), NAD(P)H:quinone oxidoreductase 1 (NQO1) and glutathione S-transferases (GSTA), in primary culture of rat hepatocytes was tested and evaluated. To show the differences in responses of tested enzymes, the common aryl hydrocarbon receptor (AhR) ligand agonist, beta-naphthoflavone (BNF), was used. Induction of CYP1A1/2 by BNF was detected at all time intervals and at all levels (i...
March 1, 2018: Acta Pharmaceutica
Luisa Cervantes-Barragan, Marco Colonna
The immune system of the intestinal tract has the challenging task of recognizing and eliminating intestinal pathogens while maintaining tolerance to dietary and commensal antigens; therefore, it must be able to sense environmental cues within the intestine and mount suitable responses dictated by their pathogenic or nonpathogenic nature. The aryl hydrocarbon receptor (AHR) was originally characterized as a chemical sensor of the environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) [12]. More recently, AHR has emerged as a major chemical sensor expressed in many intestinal immune cells that enables them to distinguish nutritional and microbial cues and is, therefore, important for development, maintenance and function of the intestinal immune system...
February 13, 2018: Current Opinion in Immunology
Iván L Csanaky, Andrew J Lickteig, Curtis D Klaassen
The effects of the most potent aryl hydrocarbon receptor (AhR) agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on bile acid (BA) homeostasis was examined in male and female wild-type and AhR-null mice shortly after 4-day exposure, rather than at a later time when secondary non-AhR dependent effects are more likely to occur. TCDD had similar effects on BA homeostasis in male and female mice. TCDD decreased the concentration of total-(Σ) BAs in liver by approximately 50% (all major BA categories except for the non-6,12-OH BAs), without decreasing the expression of the rate limiting BA synthetic enzyme (Cyp7a1) or altering the major BA regulatory pathways (FXR) in liver and intestine...
February 13, 2018: Toxicology and Applied Pharmacology
Qi Lv, Kai Wang, Simiao Qiao, Ling Yang, Yirong Xin, Yue Dai, Zhifeng Wei
Norisoboldine (NOR), a natural aryl hydrocarbon receptor (AhR) agonist, has been demonstrated to attenuate ulcerative colitis (UC) and induce the generation of Treg cells. Under UC condition, hypoxia widely exists in colonic mucosa, and secondary changes of microRNAs (miRs) expressions and glycolysis contribute to Treg differentiation. At present, we worked for exploring the deep mechanisms for NOR-promoted Treg differentiation in hypoxia and its subsequent anti-UC action from the angle of AhR/miR or AhR/glycolysis axis...
February 15, 2018: Cell Death & Disease
Zhiqing Duan, Yan Li, Lu Li
Epithelial-to-mesenchymal transition (EMT) is believed to play key roles in the process of cancer metastasis. The molecular changes during EMT are characterized by the down-regulation of epithelial proteins, such as E-cadherin, and the up-regulation of mesenchymal proteins, such as vimentin (VIM). It has been demonstrated that L-kynurenine (L-Kyn), a physiological ligand of Aryl hydrocarbon receptor (Ahr), promotes cancer cells to metastasize. However, the effects of D-enantiomer of kynurenine, D-kynurenine (D-Kyn), on metastasis are still unclear...
February 13, 2018: Molecular and Cellular Biochemistry
Jamie E Moscovitz, Amit S Kalgutkar, Kelly Nulick, Nathaniel Johnson, Zhiwu Lin, Theunis C Goosen, Yan Weng
The potential for drug-drug interactions (DDIs) arising from transcriptional regulation of drug disposition genes via activation of nuclear receptors (NRs) such as pregnane X receptor (PXR), constitutive androstane receptor (CAR), and/or aryl hydrocarbon receptor (AhR) remains largely unexplored, as highlighted in a recent guidance document from the European Medicines Agency. The goal of this research was to establish PXR/CAR/AhR-specific drug metabolizing enzyme (DME) and transporter gene expression signatures in sandwich-cultured cryopreserved human hepatocytes using selective activators of PXR (rifampin), CAR (CITCO) and AhR (omeprazole)...
February 12, 2018: Journal of Pharmacology and Experimental Therapeutics
Songyan Zhang, Shuaizhang Li, Zhiguang Zhou, Hualing Fu, Li Xu, Heidi Qunhui Xie, Bin Zhao
Airborne persistent toxic substances are associated with health impacts resulting from air pollution, e.g. dioxins, dioxin-like polychlorinated biphenyls and certain polycyclic aromatic hydrocarbons (PAHs), which activate aryl hydrocarbon receptor (AhR) and thereby produce the adverse outcomes. Thus, a bioassay for evaluating AhR activation is required for the risk assessment of ambient-air samples, and for this purpose, we developed a new and sensitive recombinant mouse hepatoma cell line, CBG2.8D, in which a novel luciferase-reporter plasmid containing 2 copies of a newly designed dioxin-responsive domain and a minimal promoter derived from a native gene were integrated...
February 13, 2018: Environmental Science & Technology
Joo-Hung Park, Jeong-Min Lee, Eun-Jin Lee, Da-Jeong Kim, Won-Bhin Hwang
Various amino acids regulate cell growth and differentiation. In the present study, we examined the ability of HT-29 cells to differentiate into goblet cells in RPMI and DMEM which are largely different in the amounts of numerous amino acids. Most of the HT-29 cells differentiated into goblet cells downregulating the stem cell marker Lgr5 when cultured in DMEM, but remained undifferentiated in RPMI. The goblet cell differentiation in DMEM was inhibited by 1-methyl-tryptophan (1-MT), an inhibitor of indoleamine 2,3 dioxygenase-1 which is the initial enzyme in tryptophan metabolism along the kynurenine (KN) pathway, whereas tryptophan and KN induced goblet cell differentiation in RPMI...
February 13, 2018: Oncology Reports
Yasuhiro Ishihara, Mayumi Tsuji, Christoph F A Vogel
The aryl-hydrocarbon receptor repressor (AhRR) negatively regulates aryl-hydrocarbon receptor (AhR) signaling via its inhibitory transactivation. AhR is well known to suppress adipocyte differentiation, but the function of AhRR during adipogenesis is unclear. The purpose of this study was to investigate the role of AhRR in adipocyte differentiation using 3T3-L1 cells. During the early phase of differentiation, AhRR expression was transiently induced, but throughout the entire differentiation process, low levels of AhR expression were maintained...
February 9, 2018: Archives of Biochemistry and Biophysics
Yuying Liu, Jiadi Lv, Jinyan Liu, Xiaoyu Liang, Xun Jin, Jing Xie, Le Zhang, Degao Chen, Roland Fiskesund, Ke Tang, Jingwei Ma, Huafeng Zhang, Wenqian Dong, Siqi Mo, Tianzhen Zhang, Feiran Cheng, Yabo Zhou, Qingzhu Jia, Bo Zhu, Yan Kong, Jun Guo, Haizeng Zhang, Zhuo-Wei Hu, Xuetao Cao, F Xiao-Feng Qin, Bo Huang
Dynamic interaction with the immune system profoundly regulates tumor cell dormancy. However, it is unclear how immunological cues trigger cancer cell-intrinsic signaling pathways for entering into dormancy. Here, we show that IFN-β treatment induced tumor-repopulating cells (TRC) to enter dormancy through an indolamine 2,3-dioxygenase/kynurenine/aryl hydrocarbon receptor/p27-dependent (IDO/Kyn/AhR/p27-dependent) pathway. Strategies to block this metabolic circuitry did not relieve dormancy, but led to apoptosis of dormant TRCs in murine and human melanoma models...
February 12, 2018: Journal of Clinical Investigation
Yong Wei, Zheng Zhang, Guotao Chen, Leilei Zhu, Hesong Jiang, Baibing Yang, Yun Chen, Yutian Dai, Quanbing Chen
OBJECTIVES: The association between aryl hydrocarbon receptor gene (AhR) polymorphism and male infertility risk remains conflicting. We conducted a meta-analysis to examine the AhR Arg554Lys polymorphism in relation to the susceptibility to male infertility. STUDY DESIGN: Studies concerning the association between AHR polymorphism and male infertility were searched and related information were extracted from the included studies. The STATA 12.0 software was used to perform a meta-analysis...
January 31, 2018: European Journal of Obstetrics, Gynecology, and Reproductive Biology
Nirmal K Roy, Allison Candelmo, Melissa DellaTorre, R Christopher Chambers, Arthur Nádas, Isaac Wirgin
Atlantic sturgeon and shortnose sturgeon co-occur in many estuaries along the Atlantic Coast of North America. Both species are protected under the U.S. Endangered Species Act and internationally on the IUCN Red list and by CITES. Early life-stages of both sturgeons may be exposed to persistent aromatic hydrocarbon contaminants such as PCBs and PCDD/Fs which are at high levels in the sediments of impacted spawning rivers. Our objective was to compare the PCBs and TCDD sensitivities of both species with those of other fishes and to determine if environmental concentrations of these contaminants approach those that induce toxicity to their young life-stages under controlled laboratory conditions...
February 2, 2018: Aquatic Toxicology
Jo-Anne E Cavanagh, Katherine Trought, Caroline Mitchell, Grant Northcott, Louis A Tremblay
The use of biosolids as a soil conditioner and fertiliser is hindered by the limited knowledge on the risks of micro-contaminants they contain. This study investigated the binding of six organic contaminants commonly found in biosolids, to the estrogen (ER), androgen (AR), aryl hydrocarbon (AhR), and transthyretin (TTR) receptors and their redox activity. Triclosan (TCS), bisphenol-A (BPA), and technical nonylphenol (TNP) had affinity for the TTR with relative potencies of 0.3, 0.03, and 0.076 respectively...
February 7, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Young-Chae Kim, Sunmi Seok, Sangwon Byun, Bo Kong, Yang Zhang, Grace Guo, Wen Xie, Jian Ma, Byron Kemper, Jongsook Kim Kemper
Phosphatidylcholines (PC) and S-adenosylmethionine (SAM) are critical determinants of hepatic lipid levels, but how their levels are regulated is unclear. Here, we show that Pemt and Gnmt, key one-carbon cycle genes regulating PC/SAM levels, are downregulated after feeding, leading to decreased PC and increased SAM levels, but these effects are blunted in small heterodimer partner (SHP)-null or FGF15-null mice. Further, aryl hydrocarbon receptor (AhR) is translocated into the nucleus by insulin/PKB signaling in the early fed state and induces Pemt and Gnmt expression...
February 7, 2018: Nature Communications
Chin-Shiu Huang, Haw-Wen Chen, Tzu-Yu Lin, Ai-Hsuan Lin, Chong-Kuei Lii
ETHNOPHARMACOLOGICAL RELEVANCE: Shikonin, a naphthoquinone pigment abundant in the root of the Chinese herb Lithospermum erythrorhizon, has been widely used to treat inflammatory diseases for thousands of years. Whether shikonin changes drug metabolism remains unclear. AIM OF THE STUDY: We investigated whether shikonin modulates the expression of hepatic drug-metabolizing enzymes and transporters as well as the possible mechanisms of this action. MATERIALS AND METHODS: Primary hepatocytes isolated from Sprague-Dawley rats were treated with 0-2 μM shikonin and the protein and mRNA levels of drug-metabolizing enzymes and transporters as well as the activation of aryl hydrocarbon receptor (AhR) and NF-E2-related factor 2 (Nrf2) were determined...
January 25, 2018: Journal of Ethnopharmacology
Jin Yang, Yanli Liu, Huitao Zhang, Hongjie Zhang, Wubin Wang, Yanfeng Fan
Coke oven emissions (COE) containing polycyclic aromatic hydrocarbons (PAHs) are predominant toxic constituents of particulate air pollution that have been linked to increased risk of lung cancer. Aberrant DNA methylation is one of the best known epigenetic changes in human cancers and healthy subjects exposed to carcinogens. The purpose of this study is to explore the factors influencing the methylation of long interspersed nuclear element-1 (LINE-1) and aryl-hydrocarbon receptor repressor (AhRR) in coke oven workers...
February 2018: Mutation Research
Breann T Colter, Helen Frances Garber, Sheila M Fleming, Jocelyn Phillips Fowler, Gregory D Harding, Molly Kromme Hooven, Amy Ashworth Howes, Smitha Krishnan Infante, Anna L Lang, Melinda Curran MacDougall, Melinda Stegman, Kelsey Rae Taylor, Christine Perdan Curran
Polychlorinated biphenyls (PCBs) are persistent organic pollutants known to cause adverse health effects and linked to neurological deficits in both human and animal studies. Children born to exposed mothers are at highest risk of learning and memory and motor deficits. We developed a mouse model that mimics human variation in the aryl hydrocarbon receptor and cytochrome P450 1A2 (CYP1A2) to determine if genetic variation increases susceptibility to developmental PCB exposure. In our previous studies, we found that high-affinity AhrbCyp1a2(-/-) and poor-affinity AhrdCyp1a2(-/-) knockout mice were most susceptible to learning and memory deficits following developmental PCB exposure compared with AhrbCyp1a2(+/+) wild type mice (C57BL/6J strain)...
January 30, 2018: Neurotoxicology
Wihan Pheiffer, Laura P Quinn, Hindrik Bouwman, Nico J Smit, Rialet Pieters
Soweto and Lenasia, the most densely populated area of South Africa, is simultaneously a thriving metropolis, with a fair share of people still living in squalor conditions directly dependant on the natural resources. Because of industrialisation the populace and environment in this urban area are exposed to various pollutants. The aquatic environment was selected as a proxy to study the effect of industrial pollution in this area. The concentrations, source identification, and various environmental risks of polycyclic aromatic hydrocarbons (PAHs) were determined in sediments of the upper reaches of the Klip River...
February 5, 2018: Ecotoxicology
Laetitia Dou, Stéphane Poitevin, Marion Sallée, Tawfik Addi, Bertrand Gondouin, Nathalie McKay, Michael S Denison, Noémie Jourde-Chiche, Ariane Duval-Sabatier, Claire Cerini, Philippe Brunet, Françoise Dignat-George, Stéphane Burtey
Patients with chronic kidney disease (CKD) are exposed to uremic toxins and have an increased risk of cardiovascular disease. Some uremic toxins, like indoxyl sulfate, are agonists of the transcription factor aryl hydrocarbon receptor (AHR). These toxins induce a vascular procoagulant phenotype. Here we investigated AHR activation in patients with CKD and in a murine model of CKD. We performed a prospective study in 116 patients with CKD stage 3 to 5D and measured the AHR-Activating Potential of serum by bioassay...
January 22, 2018: Kidney International
Robert Bissonnette, Lakshmi S Vasist, Jonathan N Bullman, Therese Collingwood, Geng Chen, Tomoko Maeda-Chubachi
Tapinarof cream is a novel topical nonsteroidal agent that represents a unique class of anti-inflammatory molecules targeting the aryl hydrocarbon receptor. Study 201851 was an open-label, 2-cohort sequential study that assessed the systemic pharmacokinetics, safety, and efficacy of tapinarof in adults with moderate to severe atopic dermatitis. A total of 11 participants were enrolled: 5 received 2% cream, and 6 received 1% cream. Tapinarof was systemically absorbed, and measurable amounts were detected in both cohorts...
February 1, 2018: Clinical Pharmacology in Drug Development
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