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Aryl hydrocarbon receptor

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https://www.readbyqxmd.com/read/29238104/indole-3-propionic-acid-suppresses-indoxyl-sulfate-induced-expression-of-fibrotic-and-inflammatory-genes-in-proximal-tubular-cells
#1
Maimaiti Yisireyili, Kyosuke Takeshita, Shinichi Saito, Toyoaki Murohara, Toshimitsu Niwa
Indoxyl sulfate (IS) induces fibrosis and inflammation in kidneys via oxidative stress through the induction of transforming growth factor-β1 (TGF-β1) and monocyte chemotactic protein-1 (MCP-1). Furthermore, IS is a potent endogenous agonist for aryl hydrocarbon receptor (AHR), which regulates the transcription of genes such as cytochrome P450 (CYP) 1A1. Indole-3-propionic acid (IPA) is an antioxidant and has been reported to be neuroprotective. We determined whether IPA suppresses IS-induced expression of AHR, CYP1A1, TGF-β1, and MCP-1 in proximal tubular cells...
November 2017: Nagoya Journal of Medical Science
https://www.readbyqxmd.com/read/29238069/kynurenic-acid-an-ido-metabolite-controls-tsg-6-mediated-immunosuppression-of-human-mesenchymal-stem-cells
#2
Guan Wang, Kai Cao, Keli Liu, Yueqing Xue, Arthur I Roberts, Fengying Li, Yanyan Han, Arnold B Rabson, Ying Wang, Yufang Shi
Mesenchymal stem cells (MSCs) have been demonstrated to be anti-inflammatory against various immune disorders through several factors, including indoleamine 2,3-dioxygenase (IDO) and TNF-stimulated gene 6 (TSG-6). However, little is known about the necessity for both of these key immunosuppressive factors. Here we employed the mouse lipopolysaccharide (LPS)-induced acute lung injury (ALI) model, and found that IDO is necessary to achieve the effect of human umbilical cord-derived MSC (hUC-MSC)-based treatment on ALI...
December 13, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29237712/receptor-activities-of-persistent-pollutant-serum-mixtures-and-breast-cancer-risk
#3
Maria Wielsøe, Christian Bjerregaard-Olesen, Peder Kern, Eva Cecilie Bonefeld-Jørgensen
Studies on associations between persistent organic pollutants (POPs) and breast cancer risk are inconclusive. The majority of studies have evaluated the effect of single compounds, without considering multiple exposures to and interactions between different POPs. The present study aimed at evaluating breast cancer risk related to combined effects of serum POP mixtures on cellular receptor functions. Data on breast cancer cases (n=77) and controls (n=84) was collected among Greenlandic Inuit women. Serum mixtures of lipophilic POPs (lipPOPs), perfluoroalkyl acids (PFAAs), and dioxin-like POPs were extracted...
December 13, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29231728/protective-effect-of-mulberry-morus-alba-l-extract-against-benzo-a-pyrene-induced-skin-damage-through-inhibition-of-aryl-hydrocarbon-receptor-signaling
#4
Hyunju Woo, JungA Lee, Deokhoon Park, Eunsun Jung
Benzo[a]pyrene (B[a]P), a type of polycyclic aromatic hydrocarbon, is present in the atmosphere surrounding our environment. Although B[a]P is a procarcinogen, enzymatically metabolized benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE) could intercalate into DNA to form bulky BPDE-DNA adducts as an ultimate carcinogenic product in human keratinocytes. The aim of this study was to evaluate the protective effect of mulberry extract, purified from the fruit of Morus Alba L., on B[a]P-induced cytotoxicity in human keratinocytes and its mechanisms of action...
December 12, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29229632/activation-of-the-aryl-hydrocarbon-receptor-leads-to-resistance-to-egfr-tkis-in-non-small-cell-lung-cancer-by-activating-src-mediated-bypass-signaling
#5
Mingxiang Ye, Yong Zhang, Hongjun Gao, Yan Xu, Pengyu Jing, Jianxiong Wu, Xinxin Zhang, Jie Xiong, Chenfang Dong, Libo Yao, Jian Zhang, Jian Zhang
PURPOSE: The aryl hydrocarbon receptor (AhR) has been generally recognized as a ligand-activated transcriptional factor that responds to xenobiotic chemicals. Recent studies have suggested that the expression of AhR varies widely across different cancer types and cancer cell lines, but its significance in cancer treatment has yet to be clarified. EXPERIMENTAL DESIGN: AhR expression in non-small-cell lung cancer (NSCLC) was determined by Western blotting and IHC staining...
December 11, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29222397/indoxyl-sulfate-upregulates-liver-p-glycoprotein-expression-and-activity-through-aryl-hydrocarbon-receptor-signaling
#6
Tacy Santana Machado, Stéphane Poitevin, Pascale Paul, Nathalie McKay, Noémie Jourde-Chiche, Tristan Legris, Annick Mouly-Bandini, Françoise Dignat-George, Philippe Brunet, Rosalinde Masereeuw, Stéphane Burtey, Claire Cerini
In patients with CKD, not only renal but also, nonrenal clearance of drugs is altered. Uremic toxins could modify the expression and/or activity of drug transporters in the liver. We tested whether the uremic toxin indoxyl sulfate (IS), an endogenous ligand of the transcription factor aryl hydrocarbon receptor, could change the expression of the following liver transporters involved in drug clearance: SLC10A1, SLC22A1, SLC22A7, SLC47A1, SLCO1B1, SLCO1B3, SLCO2B1, ABCB1, ABCB11, ABCC2, ABCC3, ABCC4, ABCC6, and ABCG2 We showed that IS increases the expression and activity of the efflux transporter P-glycoprotein (P-gp) encoded by ABCB1 in human hepatoma cells (HepG2) without modifying the expression of the other transporters...
December 8, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29221954/total-particulate-matter-from-cigarette-smoke-disrupts-vascular-development-in-zebrafish-brain-danio-rerio
#7
Andrey Massarsky, G L Prasad, Richard T Di Giulio
Several studies have demonstrated zebrafish as a useful high-throughput in-vivo model to study the effects of cigarette smoke on early development. It has been shown previously that exposure of zebrafish to cigarette smoke total particulate matter (TPM) leads to several adverse physiological aberrations, including heart deformities and improper angiogenesis. Consequently, this study investigated the effects of TPM on cardiovascular development in zebrafish that were exposed to increasing concentrations of TPM based upon nicotine content from 6h post fertilization (hpf) up to 72hpf...
December 5, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29214529/a-rapid-and-reagent-free-bioassay-for-the-detection-of-dioxin-like-compounds-and-other-aryl-hydrocarbon-receptor-ahr-agonists-using-autobioluminescent-yeast
#8
Tingting Xu, Anna Young, Enolia Marr, Gary Sayler, Steven Ripp, Dan Close
An autonomously bioluminescent Saccharomyces cerevisiae BLYAhS bioreporter was developed in this study for the simple and rapid detection of dioxin-like compounds (DLCs) and aryl hydrocarbon receptor (AhR) agonists. This recombinant yeast reporter was based on a synthetic bacterial luciferase reporter gene cassette (lux) that can produce the luciferase as well as the enzymes capable of self-synthesizing the requisite substrates for bioluminescent production from endogenous cellular metabolites. As a result, bioluminescent signal production is generated continuously and autonomously without cell lysis or exogenous reagent addition...
December 6, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/29212263/combination-of-betulinic-acid-and-chidamide-inhibits-acute-myeloid-leukemia-by-suppression-of-the-hif1%C3%AE-pathway-and-generation-of-reactive-oxygen-species
#9
Hongyu Zhang, Ling Li, Min Li, Xiaodong Huang, Weiguo Xie, Wei Xiang, Paul Yao
Acute myeloid leukemia (AML) is a heterogeneous disorder of the hematopoietic system with no common genetic "Achilles heel" that can be targeted. Most patients respond well to standard therapy, while a majority relapse, and development of an effective therapy for AML patients is still urgently needed. In this study, we demonstrated that betulinic acid (BA) significantly increased Aryl hydrocarbon receptor (AHR) expression through demethylation on the AHR promoter in AML cells, and the increased AHR expression interacts with and sequesters ARNT, subsequently suppressing hypoxia-inducible factor-1α (HIF1α) pathway...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29209748/monitoring-cytochrome-p450-activity-in-living-hepatocytes-by-chromogenic-substrates-in-response-to-drug-treatment-or-during-cell-maturation
#10
Jannick Theobald, Xinlai Cheng, Ali Ghanem, Haristi Gaitantzi, Guangqi Song, Edda Klipp, Judith Wodke, Holger Becker, Ralf Mrowka, Katja Breitkopf-Heinlein, Steven Dooley, Stefan Wölfl
The metabolic activity of hepatocytes is a central prerequisite for drug activity and a key element in drug-drug interaction. This central role in metabolism largely depends on the activity of the cytochrome P450 (CYP450) enzyme family, which is not only dependent on liver cell maturation but is also controlled in response to drug and chemical exposure. Here, we report the use of VividDye fluorogenic CYP450 substrates to directly measure and continuously monitor metabolic activity in living hepatocytes. We observed time- and dose-dependent correlation in response to established and putative CYP450 inducers acting through the aryl hydrocarbon receptor and drug combinations...
December 5, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29207040/aryl-hydrocarbon-receptor-inhibits-inflammation-in-dss%C3%A2-induced-colitis-via-the-mk2-p%C3%A2-mk2-ttp-pathway
#11
Qimeng Wang, Kunqiu Yang, Bin Han, Baifa Sheng, Jiuheng Yin, Aimin Pu, Liangzi Li, Lihua Sun, Min Yu, Yuan Qiu, Weidong Xiao, Hua Yang
The pathogenesis of inflammatory bowel disease (IBD) is believed to be associated with the abnormal expression of inflammatory factors. The aryl hydrocarbon receptor (AhR) is a ligand‑dependent transcription factor, which can suppress the inflammatory response and attenuate experimental colitis. However, the detailed mechanism underlying the effects of AhR remains unclear. The present study investigated the role of AhR in the pathogenesis of IBD. Colitis was induced in mice by administration of 3% dextran sulphate sodium (DSS) for 7 days...
November 17, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29203322/effects-of-in-ovo-exposure-to-benzo-k-fluoranthene-bkf-on-cyp1a-expression-and-promoter-methylation-in-developing-chicken-embryos
#12
Jonas Brandenburg, Jessica A Head
Polycyclic aromatic hydrocarbons (PAHs) are toxic environmental pollutants that are potent teratogens. Recent research suggests that early life exposure to PAHs can affect health outcomes later in life. Some of these latent responses may be mediated by epigenetic mechanisms such as DNA methylation. The role of DNA methylation in regulating responses to PAHs in birds is currently unknown. Here, we assess the effect of in ovo exposure to the model PAH, benzo[k]fluoranthene (BkF), on aryl hydrocarbon receptor (AHR) mediated cytochrome P4501A (CYP1A) gene expression and promoter methylation in chicken embryos...
December 1, 2017: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/29197979/genetic-differences-in-the-aryl-hydrocarbon-receptor-and-cyp1a2-affect-sensitivity-to-developmental-polychlorinated-biphenyl-exposure-in-mice-relevance-to-studies-of-human-neurological-disorders
#13
Kelsey Klinefelter, Molly Kromme Hooven, Chloe Bates, Breann T Colter, Alexandra Dailey, Smitha Krishnan Infante, Izabela Kania-Korwel, Hans-Joachim Lehmler, Alejandro López-Juárez, Clare Pickering Ludwig, Christine Perdan Curran
Polychlorinated biphenyls (PCBs) are persistent organic pollutants that remain a human health concern with newly discovered sources of contamination and ongoing bioaccumulation and biomagnification. Children exposed during early brain development are at highest risk of neurological deficits, but highly exposed adults reportedly have an increased risk of Parkinson's disease. Our previous studies found allelic differences in the aryl hydrocarbon receptor and cytochrome P450 1A2 (CYP1A2) affect sensitivity to developmental PCB exposure, resulting in cognitive deficits and motor dysfunction...
December 2, 2017: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://www.readbyqxmd.com/read/29197551/allelic-variants-of-the-aryl-hydrocarbon-receptor-differentially-influence-uvb-mediated-skin-inflammatory-responses-in-skh1-mice
#14
Kayla J Smith, Iain A Murray, Jacob A Boyer, Gary H Perdew
The mouse strain SKH1 is widely used in skin research due to its hairless phenotype and intact immune system. Due to the complex nature of aryl hydrocarbon receptor (AHR) function in the skin, the development of additional in vivo models is necessary to study its role in cutaneous homeostasis and pathology. Variants of the Ah allele, exist among different mouse strains. The Ahb-1 and Ahd alleles express high and low affinity ligand binding forms of the AHR, respectively. The outbred SKH1 mice express the Ahb-2 and/or Ahd alleles...
November 29, 2017: Toxicology
https://www.readbyqxmd.com/read/29197056/current-state-of-yusho-and-prospects-for-therapeutic-strategies
#15
Chikage Mitoma, Hiroshi Uchi, Kiyomi Tsukimori, Takashi Todaka, Jumboku Kajiwara, Takayuki Shimose, Manabu Akahane, Tomoaki Imamura, Masutaka Furue
The mass food poisoning incident yusho occurred in Japan in 1968. It was caused by the ingestion of rice bran oil contaminated with polychlorinated biphenyls and various dioxins and dioxin-like compounds including polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDFs). Notably, PCDFs were found to contribute to approximately 65% of the total toxicity equivalent in the blood of yusho patients. Lipophilic dioxins are retained in the body for a longer period than previously estimated. Victims suffered from characteristic skin manifestations associated with non-specific systemic symptoms, neurological symptoms, and respiratory symptoms...
December 1, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29194499/emotion-recognition-associated-with-polymorphism-in-oxytocinergic-pathway-gene-arnt2
#16
Daniel Hovey, Susanne Henningsson, Diana S Cortes, Tanja Bänziger, Anna Zettergren, Jonas Melke, Håkan Fischer, Petri Laukka, Lars Westberg
The ability to correctly understand the emotional expression of another person is essential for social relationships and appears to be a partly inherited trait. The neuropeptides oxytocin and vasopressin have been shown to influence this ability as well as face processing in humans. Here, recognition of the emotional content of faces and voices, separately and combined, was investigated in 492 subjects, genotyped for 25 single nucleotide polymorphisms (SNPs) in eight genes encoding proteins important for oxytocin and vasopressin neurotransmission...
November 28, 2017: Social Cognitive and Affective Neuroscience
https://www.readbyqxmd.com/read/29194351/identification-of-a-raloxifene-analog-that-promotes-ahr-mediated-apoptosis-in-cancer-cells
#17
Hyo Sang Jang, Martin Pearce, Edmond F O'Donnell, Bach Duc Nguyen, Lisa Truong, Monica J Mueller, William H Bisson, Nancy I Kerkvliet, Robert L Tanguay, Siva Kumar Kolluri
We previously reported that raloxifene, an estrogen receptor modulator, is also a ligand for the aryl hydrocarbon receptor (AhR). Raloxifene induces apoptosis in estrogen receptor-negative human cancer cells through the AhR. We performed structure-activity studies with seven raloxifene analogs to better understand the structural requirements of raloxifene for induction of AhR-mediated transcriptional activity and apoptosis. We identified Y134 as a raloxifene analog that activates AhR-mediated transcriptional activity and induces apoptosis in MDA-MB-231 human triple negative breast cancer cells...
December 1, 2017: Biology
https://www.readbyqxmd.com/read/29192765/development-of-an-in-vitro-based-risk-assessment-framework-for-predicting-ambient-particulate-matter-bound-polycyclic-aromatic-hydrocarbon-activated-toxicity-pathways
#18
Wei-Chun Chou, Chin-Yu Hsu, Chia-Chi Ho, Jui-Hua Hsieh, Hung-Che Chiang, Tsui-Chun Tsou, Yu-Cheng Chen, Pinpin Lin
Polycyclic aromatic hydrocarbons (PAHs) are widely distributed throughout the atmosphere as mixtures attached to ambient particulate matter (PM). PAHs usually elicit similar toxicological pathways but do so with varying levels of efficacy. In this study, we utilized high-throughput screening (HTS) in vitro data of PAHs to predict health risks associated with coarse and fine PM. PM samples with 22 PAH compounds obtained from residential areas close to industrial parks in central Taiwan were analyzed. On the basis of the PM-bound PAH concentrations and their activities reported in HTS assays, we developed a probabilistic model for estimating cumulative exposure of humans to PAHs...
December 1, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/29191726/essential-oils-of-culinary-herbs-and-spices-display-agonist-and-antagonist-activities-at-human-aryl-hydrocarbon-receptor-ahr
#19
Iveta Bartoňková, Zdeněk Dvořák
Essential oils (EOs) of culinary herbs and spices are used to flavor, color and preserve foods and drinks. Dietary intake of EOs is significant, deserving an attention of toxicologists. We examined the effects of 31 EOs of culinary herbs and spices on the transcriptional activity of human aryl hydrocarbon receptor (AhR), which is a pivotal xenobiotic sensor, having also multiple roles in human physiology. Tested EOs were sorted out into AhR-inactive ones (14 EOs) and AhR-active ones, including full agonists (cumin, jasmine, vanilla, bay leaf), partial agonists (cloves, dill, thyme, nutmeg, oregano) and antagonists (tarragon, caraway, turmeric, lovage, fennel, spearmint, star anise, anise)...
November 27, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29191105/curcumin-and-its-derivatives-inhibit-2-3-7-8-tetrachloro-dibenzo-p-dioxin-induced-expression-of-drug-metabolizing-enzymes-through-aryl-hydrocarbon-receptor-mediated-pathway
#20
Rika Nakai, Shun Fukuda, Masaya Kawase, Yoko Yamashita, Hitoshi Ashida
Certain dioxins, including 2,3,7,8,-tetrachloro-dibenzo-p-dioxin (TCDD), are exogenous ligands for an aryl hydrocarbon receptor (AhR) and induces various drug-metabolizing enzymes. In this study, we examined the effect of curcumin on expression of drug-metabolizing enzymes through the AhR and NF-E2 related factor 2 (Nrf2) pathways. Curcumin dose-dependently inhibited TCDD-induced expression of phase I enzyme cytochrome P450 1A1 (CYP1A1) and phase II enzymes NAD(P)H:quinone oxidoreductase-1 (NQO1) and heme oxygenase 1 (HO-1) but not tert-butyl hydroquinone-induced NQO1 and HO-1, suggesting that curcumin inhibited only AhR pathway, but not Nrf2 one directly...
December 1, 2017: Bioscience, Biotechnology, and Biochemistry
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