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Aryl hydrocarbon receptor

Yu Zhou, Shujin Li, Lulin Huang, Yeming Yang, Lin Zhang, Mu Yang, Wenjing Liu, Kim Ramasamy, Zhilin Jiang, Periasamy Sundaresan, Xianjun Zhu, Zhenglin Yang
No abstract text is available yet for this article.
June 21, 2018: Human Molecular Genetics
Fekadu Yadetie, Xiaokang Zhang, Eileen Marie Hanna, Libe Aranguren-Abadía, Marta Eide, Nello Blaser, Morten Brun, Inge Jonassen, Anders Goksøyr, Odd André Karlsen
Polycyclic aromatic hydrocarbons such as benzo[a]pyrene (BaP) that activate the aryl hydrocarbon receptor (Ahr) pathway, and endocrine disruptors acting through the estrogen receptor pathway are among environmental pollutants of major concern. In this work, we exposed Atlantic cod (Gadus morhua) precision-cut liver slices (PCLS) to BaP (10 nM and 1000 nM), ethynylestradiol (EE2) (10 nM and 1000 nM), and equimolar mixtures of BaP and EE2 (10 nM and 1000 nM) for 48 h, and performed RNA-Seq based transcriptome mapping followed by systematic bioinformatics analyses...
June 7, 2018: Aquatic Toxicology
Jun Terashima, Yoko Jimma, Keiko Jimma, Shuko Hakata, Maako Yachi, Wataru Habano, Shogo Ozawa
Most of cytochrome P450 (CYP) expressions are regulated by nuclear receptors. The regulation pathways of transcription are activated by binding of the ligand to the receptor. Many combination of CYPs and nuclear receptors in transcriptional regulation have been reported. However, we have reported that the combination changes depending on culture condition on the same type of cells. The regulation pathway of CYP1A expression is different between 2D monolayer cultured cells and 3D spheroids of human liver cancer cells...
April 24, 2018: Drug Metabolism and Pharmacokinetics
Wensi Xu, Shunya Saiki, Takumi Myojin, Yujia Liu, Beiwei Zhu, Yoshiyuki Murata, Hitoshi Ashida, Makoto Tsunenaga, Yoshimasa Nakamura
Lycii Fructus is the dried ripe fruits of Lycium chinense and L. barbarum, which has long been used as a traditional food material in East Asia. The purpose of this study was to investigate the role of the indirect antioxidative action in the Lycii fructus extract (LFE)-induced cytoprotective effect in vitro. LFE significantly enhanced the expression of the drug-metabolizing enzyme genes and intracellular glutathione level in mouse hepatoma Hepa1c1c7 cells. LFE stimulated the nuclear translocation of aryl hydrocarbon receptor as well as nuclear factor (erythroid-derived 2)-like 2...
June 18, 2018: Bioscience, Biotechnology, and Biochemistry
Selma Mahiout, Sara Giani Tagliabue, Atefeh Nasri, Iyekhoetin Matthew Omoruyi, Lars Pettersson, Laura Bonati, Raimo Pohjanvirta
The mediator of dioxin toxicity, aryl hydrocarbon receptor (AHR), has also important physiological functions. Selective AHR modulators (SAHRMs) share some effects of dioxins, except for their marked toxicity. We recently characterised toxicologically two novel SAHRMs, prodrugs IMA-08401 and IMA-07101 in rats, demonstrating that they are far less deleterious than the most toxic AHR-agonist, TCDD. Here, we analysed the in vitro toxicity and in silico AHR binding of the respective active, deacetylated metabolites, IMA-06201 (N-ethyl-N-phenyl-5-chloro-1,2-dihydro-4-hydroxy-1-methyl-2-oxo-quinoline-3-carboxamide) and IMA-06504 (N-(4-trifluoromethylphenyl)-1,2-dihydro-4-hydroxy-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide)...
June 13, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Ondrej Zenata, Zdenek Dvorak, Radim Vrzal
Mycophenolate Mofetil (MYC) is a transplant drug used to prevent rejection in heart and kidneys transplant patients. Inosine monophosphate dehydrogenase (IMPDH), an enzyme involved in de novo synthesis of guanosine nucleotides, was considered as a primary target for MYC. Recently, we described that MYC was activates aryl hydrocarbon receptor and it antagonizes glucocorticoid receptor. Here we describe an androgen receptor (AR) as another off-target for MYC. We found that MYC increased basal and dihydrotestosterone (DHT)-inducible AR-dependent luciferase activity in AIZ-AR cells...
2018: Journal of Cancer
Mónica Sierra-Martinez, Leticia Hernández-Cadena, José Rubén García-Sánchez, Gustavo Acosta-Altamirano, Carmen Palacios-Reyes, Patricia García Alonso-Themann, Liliana García-Ortiz, Laura Itzel Quintas-Granados, Octavio Daniel Reyes-Hernández
Context: Several factors contribute to the increase in breast cancer (BC) incidence, such as lifetime exposure to estrogen, early menarche and older ages at first birth, menopause, and the increased prevalence of postmenopausal obesity. In fact, there is an association between an increased BC risk and elevated estrogen levels, which may be involved in carcinogenesis via the estrogen receptor alpha (ERα) encoded by the ESR1 gene. Interestingly, there is an antagonistic relationship between ERα and the aryl hydrocarbon receptor (AhR) in BC cells...
April 2018: Journal of Cancer Research and Therapeutics
Maria Larsson, Monika M Lam, Patrick van Hees, John P Giesy, Magnus Engwall
An important concern regarding sites contaminated with polycyclic aromatic compounds (PACs) is the risk of groundwater contamination by release of the compounds from soils. The goal of this study was to investigate the occurrence and leachability of 77 PACs including polycyclic aromatic hydrocarbons (PAHs) and heterocyclic aromatic compounds (NSO-PACs) among total aryl hydrocarbon receptor (AhR) agonists in soils from historical contaminated sites. A novel approach combining chemical and bioanalytical methods in combination with characterization of leachability by use of a column leaching test was used...
May 1, 2018: Science of the Total Environment
Jhimmy Talbot, Raphael S Peres, Larissa G Pinto, Rene D R Oliveira, Kalil A Lima, Paula B Donate, Jaqueline R Silva, Bernard Ryffel, Thiago M Cunha, José C Alves-Filho, Foo Y Liew, Paulo Louzada-Junior, Fernando de Queiroz Cunha
BACKGROUND: Epidemiologic studies have highlighted the association of environmental factors with the development and progression of autoimmune and chronic inflammatory diseases. Among the environmental factors, smoking has been associated with increased susceptibility and poor prognosis in rheumatoid arthritis (RA). However, the immune and molecular mechanism of smoking-induced arthritis aggravation remains unclear. The transcription factor aryl hydrocarbon receptor (AHR) regulates the generation of Th17 cells, CD4 T cells linked the development of autoimmune diseases...
June 8, 2018: Arthritis Research & Therapy
David Hutin, Laura Tamblyn, Alvin Gomez, Giulia Grimaldi, Helen Soedling, Tiffany Cho, Shaimaa Ahmed, Christin Lucas, Chakravarthi Kanduri, Denis M Grant, Jason Matthews
The aryl hydrocarbon receptor (AHR) mediates the toxic effects of dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDD), which include thymic atrophy, steatohepatitis, and a lethal wasting syndrome in laboratory rodents. Although the mechanisms of dioxin toxicity remain unknown, AHR signaling in hepatocytes is necessary for dioxin-induced liver toxicity. We previously reported that loss of TCDD-inducible poly(ADP-ribose) polymerase (TIPARP/PARP7/ARTD14), an AHR target gene and mono-ADP-ribosyltransferase, increases the sensitivity of mice to dioxin-induced toxicities...
June 4, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Suping Chen, Jing Yang, Yang Zhang, Chunyan Duan, Qing Liu, Zhengyun Huang, Ying Xu, Liang Zhou, Guoqiang Xu
Dysregulation of the circadian rhythm is associated with many diseases, including diabetes, obesity, and cancer. Aryl hydrocarbon receptor nuclear translocator-like protein 1 (Arntl or Bmal1) is the only clock gene whose loss disrupts circadian locomotor behavior in constant darkness. BMAL1 levels are affected by proteasomal inhibition and by several enzymes in the ubiquitin-proteasome system, but the exact molecular mechanism remains unclear. Here, using immunoprecipitation and MS analyses, we discovered an interaction between BMAL1 and ubiquitin-conjugating enzyme E2 O (UBE2O), an E3-independent, E2-ubiquitin-conjugating enzyme (i...
June 5, 2018: Journal of Biological Chemistry
Akiko Hashimoto-Hachiya, Gaku Tsuji, Mika Murai, Xianghong Yan, Masutaka Furue
Rhodiola species are antioxidative, salubrious plants that are known to inhibit oxidative stress induced by ultraviolet and γ-radiation in epidermal keratinocytes. As certain phytochemicals activate aryl hydrocarbon receptors (AHR) or OVO-like 1 (OVOL1) to upregulate the expression of epidermal barrier proteins such as filaggrin (FLG), loricrin (LOR), and involucrin (IVL), we investigated such regulation by Rhodiola crenulata root extract (RCE). We demonstrated that RCE induced FLG and LOR upregulation in an AHR-OVOL1-dependent fashion...
June 4, 2018: International Journal of Molecular Sciences
Jon A Doering, Steve B Wiseman, John P Giesy, Markus Hecker
Dioxin-like compounds (DLCs) elicit adverse effects through activation of the aryl hydrocarbon receptor (AHR). Prior investigations demonstrated that sensitivity to activation of AHR1 in an in vitro AHR transactivation assay is predictive of early life stage mortality among birds. The present study investigated the link between sensitivity to activation of AHR1s and AHR2s and early life stage mortality among fishes. A significant, linear relationship was demonstrated between sensitivity to activation of AHR2 and early life stage mortality among nine fishes, while no relationship was found for AHR1...
June 4, 2018: Environmental Science & Technology
Masafumi Takeno, Shinya Kitagawa, Junpei Yamanaka, Mayumi Teramoto, Haruka Tomita, Naohiro Shirai, Saotomo Itoh, Shigeaki Hida, Kazuichi Hayakawa, Kikuo Onozaki, Takemasa Takii
The risk of rheumatoid arthritis (RA) is linked to environmental and genetic factors. Cigarette smoking is an established environmental risk factor for the disease that contributes to its development and severity. Previously, we found that cigarette smoke condensate (CSC), both mainstream and sidestream, aggravates collagen type II-induced arthritis (CIA), which was observed following either intraperitoneal inoculation or nasal exposure. In the present study, we aimed to identify the compound in CSC, which aggravates CIA...
2018: Biological & Pharmaceutical Bulletin
Jiajun Zhou, Qiang Zhang, Joseph E Henriquez, Robert B Crawford, Norbert E Kaminski
The aryl hydrocarbon receptor (AHR) is a cytosolic ligand-activated transcription factor involved in xenobiotic sensing, cell cycle regulation and cell development. In humans, the activation of AHR by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a high affinity AHR-ligand, impairs the secretion of immunoglobulin M (IgM) to suppress humoral immunity. However, the mechanisms bridging the activation of AHR and the impairment of IgM secretion by human primary B cells remain poorly understood. Recent transcriptomic analysis revealed upregulation of lymphocyte-specific protein tyrosine kinase (LCK) in AHR activated human primary B cells...
May 31, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Sarah Dubaisi, Kathleen G Barrett, Hailin Fang, Jorge Guzman-Lepe, Alejandro Soto-Gutierrez, Thomas A Kocarek, Melissa Runge-Morris
Cytosolic sulfotransferases (SULTs) are expressed during early life and therefore metabolize endogenous and xenobiotic chemicals during development. Little is currently known about the regulation of individual SULTs in the developing human liver. We characterized SULT expression in primary cultures of human fetal hepatocytes and the HepaRG model of liver cell differentiation. SULT1A1 (transcript variants 1 - 4), SULT1C2, SULT1C4, SULT1E1, and SULT2A1 were the most abundant transcripts in human fetal hepatocytes...
June 1, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Anna Henry Borton, Bryan L Benson, Lee E Neilson, Ashley Saunders, M Amer Alaiti, Alex Y Huang, Mukesh K Jain, Aaron Proweller, Diana L Ramirez-Bergeron
BACKGROUND: Limb ischemia resulting from peripheral vascular disease is a common cause of morbidity. Vessel occlusion limits blood flow, creating a hypoxic environment that damages distal tissue, requiring therapeutic revascularization. Hypoxia-inducible factors (HIFs) are key transcriptional regulators of hypoxic vascular responses, including angiogenesis and arteriogenesis. Despite vascular smooth muscle cells' (VSMCs') importance in vessel integrity, little is known about their functional responses to hypoxia in peripheral vascular disease...
June 1, 2018: Journal of the American Heart Association
Maddalena Napolitano, Cataldo Patruno
Aryl hydrocarbon receptor (AhR) is a transcription factor expressed in all skin cells type. It responds to exogenous and endogenous chemicals by inducing/repressing the expression of several genes with toxic or protective effects in a wide range of species and tissues. In healthy skin, AhR signalling contributes to keratinocytes differentiation, skin barrier function, skin pigmentation, and mediates oxidative stress. In the last years, some studies have shown that AhR seems to be involved in the pathogenesis of some skin diseases, even if the currently available data are contradictory...
July 2018: Medical Hypotheses
Pedro Marques, Sayka Barry, Amy Ronaldson, Arla Ogilvie, Helen L Storr, Peter J Goadsby, Michael Powell, Mary N Dang, Harvinder S Chahal, Jane Evanson, Ajith V Kumar, Joan Grieve, Márta Korbonits
Introduction: Germline aryl hydrocarbon receptor-interacting protein ( AIP ) mutations are responsible for 15-30% of familial isolated pituitary adenomas (FIPAs). We report a FIPA kindred with a heterozygous deletion in AIP , aiming to highlight the indications and benefits of genetic screening, variability in clinical presentations, and management challenges in this setting. Patients: An 18-year-old male was diagnosed with a clinically nonfunctioning pituitary adenoma (NFPA)...
2018: International Journal of Endocrinology
Flavia Marques DE Melo, Luciana Bastos-Rodrigues, Maria Marta Sarquis, Eitan Friedman, Luiz DE Marco
BACKGROUND/AIM: Familial multiple endocrine neoplasia type 1 (MEN1) is a rare disorder mostly associated with germline MEN1 mutations. MATERIALS AND METHODS: Genotyping of the MEN1, cyclin-dependent kinase inhibitor 1B (CDKN1B) and aryl hydrocarbon receptor-interacting protein (AIP) genes using Sanger sequencing was carried out in a family with MEN1 and the resulting germline variants genotyped in an additional 95 ethnically matched controls. RESULTS: A missense variant in AIP (p...
June 2018: Anticancer Research
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