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Smoking AND aryl hydrocarbon receptor (AHR)

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https://www.readbyqxmd.com/read/28481916/tcf21-and-the-environmental-sensor-aryl-hydrocarbon-receptor-cooperate-to-activate-a-pro-inflammatory-gene-expression-program-in-coronary-artery-smooth-muscle-cells
#1
Juyong Brian Kim, Milos Pjanic, Trieu Nguyen, Clint L Miller, Dharini Iyer, Boxiang Liu, Ting Wang, Olga Sazonova, Ivan Carcamo-Orive, Ljubica Perisic Matic, Lars Maegdefessel, Ulf Hedin, Thomas Quertermous
Both environmental factors and genetic loci have been associated with coronary artery disease (CAD), however gene-gene and gene-environment interactions that might identify molecular mechanisms of risk are not easily studied by human genetic approaches. We have previously identified the transcription factor TCF21 as the causal CAD gene at 6q23.2 and characterized its downstream transcriptional network that is enriched for CAD GWAS genes. Here we investigate the hypothesis that TCF21 interacts with a downstream target gene, the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor that mediates the cellular response to environmental contaminants, including dioxin and polycyclic aromatic hydrocarbons (e...
May 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28476168/dioxins-and-related-environmental-contaminants-increase-tdp-43-levels
#2
Peter E A Ash, Elizabeth A Stanford, Ali Al Abdulatif, Alejandra Ramirez-Cardenas, Heather I Ballance, Samantha Boudeau, Amanda Jeh, James M Murithi, Yorghos Tripodis, George J Murphy, David H Sherr, Benjamin Wolozin
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative condition that is characterized by progressive loss of motor neurons and the accumulation of aggregated TAR DNA Binding Protein-43 (TDP-43, gene: TARDBP). Increasing evidence indicates that environmental factors contribute to the risk of ALS. Dioxins, related planar polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs) are environmental contaminants that activate the aryl hydrocarbon receptor (AHR), a ligand-activated, PAS family transcription factor...
May 5, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28377982/mechanistic-insight-into-the-effects-of-aryl-hydrocarbon-receptor-activation-on-osteogenic-differentiation
#3
Chawon Yun, Joseph A Weiner, Danielle S Chun, Jonghwa Yun, Ralph W Cook, Michael S Schallmo, Abhishek S Kannan, Sean M Mitchell, Ryan D Freshman, Christian Park, Wellington K Hsu, Erin L Hsu
While inhibition of bone healing and increased rates of pseudarthrosis are known adverse outcomes associated with cigarette smoking, the underlying mechanisms by which this occurs are not well understood. Recent work has implicated the Aryl Hydrocarbon Receptor (Ahr) as one mediator of the anti-osteogenic effects of cigarette smoke (CS), which contains numerous toxic ligands for the Ahr. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) is a high-affinity Ahr ligand frequently used to evaluate Ahr pathway activation...
June 2017: Bone Reports
https://www.readbyqxmd.com/read/28285017/effects-of-the-aryl-hydrocarbon-receptor-agonist-3-methylcholanthrene-on-the-17%C3%AE-estradiol-regulated-mrna-transcriptome-of-the-rat-uterus
#4
Janina Helle, Annekathrin M Keiler, Oliver Zierau, Peggy Dörfelt, Günter Vollmer, Leane Lehmann, Sridar V Chittur, Martin Tenniswood, JoEllen Welsh, Georg Kretzschmar
Polycyclic aromatic hydrocarbons (PAHs) are products of incomplete combustion of organic compounds, abundant in exhaust fumes and cigarette smoke. They act by binding to the aryl hydrocarbon receptor (AHR) which induces expression of phase 1 and phase 2 enzymes in the liver. PAH induced AHR activation may also lead to adverse effects by modulating other pathways, for example estrogen receptor (ER) signaling in the female reproductive tract. We have investigated the effects of the PAH 3-methylcholanthrene (3-MC) on 17β-estradiol (E2) dependent signaling in the uterus of ovariectomized rats to characterize the cross talk between AHR and ER on an mRNA transcriptome wide scale...
March 8, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28254546/relb-attenuates-cigarette-smoke-extract-induced-apoptosis-in-association-with-transcriptional-regulation-of-the-aryl-hydrocarbon-receptor
#5
Matthew Iu, Michela Zago, Angela Rico de Souza, Manuella Bouttier, Swati Pareek, John H White, Qutayba Hamid, David H Eidelman, Carolyn J Baglole
Chronic obstructive pulmonary disease (COPD) is a chronic and prevalent respiratory disease caused primarily by long term inhalation of cigarette smoke. A major hallmark of COPD is elevated apoptosis of structural lung cells including fibroblasts. The NF-κB member RelB may suppress apoptosis in response to cigarette smoke, but its role in lung cell survival is not known. RelB may act as a pro-survival factor by controlling the expression of superoxide dismutase 2 (SOD2). SOD2 is also regulated by the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that suppresses cigarette smoke-induced apoptosis...
February 27, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28249752/benzo-a-pyrene-impedes-self-renewal-and-differentiation-of-mesenchymal-stem-cells-and-influences-fracture-healing
#6
Yiqing Zhou, Rong Jiang, Liqin An, Hong Wang, Sicheng Cheng, Shi Qiong, Yaguang Weng
Mesenchymal stem cells (MSCs) are implicated in the bone-forming process during fracture repair. Benzo[a]pyrene (BaP)-a cigarette smoke component and powerful motivator of the aryl hydrocarbon receptor (Ahr)-unfavorably influences bone condition and osteoblast differentiation. The first thing we noticed decreases self-renewal and differentiation of human bone marrow mesenchymal stem (hBM-MSCs) from smokers and activates Ahr signaling in MSCs by up-regulating the Ahr target gene cytochrome P450 (CYP) 1B1 expression...
February 26, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28079158/aryl-hydrocarbon-receptor-ahr-dependent-regulation-of-pulmonary-mirna-by-chronic-cigarette-smoke-exposure
#7
Sarah Rogers, Angela Rico de Souza, Michela Zago, Matthew Iu, Necola Guerrina, Alvin Gomez, Jason Matthews, Carolyn J Baglole
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor historically known for its toxic responses to man-made pollutants such as dioxin. More recently, the AhR has emerged as a suppressor of inflammation, oxidative stress and apoptosis from cigarette smoke by mechanisms that may involve the regulation of microRNA. However, little is known about the AhR regulation of miRNA expression in the lung in response to inhaled toxicants. Therefore, we exposed Ahr(-/-) and Ahr(+/-) mice to cigarette smoke for 4 weeks and evaluated lung miRNA expression by PCR array...
January 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/27977510/a-comprehensive-contribution-of-genes-for-aryl-hydrocarbon-receptor-signaling-pathway-to-hypertension-susceptibility
#8
Alexey V Polonikov, Olga Yu Bushueva, Irina V Bulgakova, Maxim B Freidin, Mikhail I Churnosov, Maria A Solodilova, Yaroslav D Shvetsov, Vladimir P Ivanov
OBJECTIVE: The present study was designed to investigate whether genetic polymorphisms of the aryl hydrocarbon receptor (AHR) signaling pathway are involved in the molecular basis of essential hypertension (EH). METHODS: A total of 2160 unrelated Russian individuals comprising 1341 EH patients and 819 healthy controls were recruited into the study. Seven common AHR pathway single-nucleotide polymorphisms (SNPs) such as rs2066853, rs2292596, rs2228099, rs1048943, rs762551, rs1056836, and rs1800566 were genotyped by TaqMan-based allele discrimination assays...
December 13, 2016: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/27849171/the-nuclear-receptor-ahr-controls-bone-homeostasis-by-regulating-osteoclast-differentiation-via-the-rank-c-fos-signaling-axis
#9
Takashi Izawa, Rieko Arakaki, Hiroki Mori, Takaaki Tsunematsu, Yasusei Kudo, Eiji Tanaka, Naozumi Ishimaru
The aryl hydrocarbon receptor (AhR) pathway plays a key role in receptor activator of NF-κB ligand (RANKL)-mediated osteoclastogenesis. However, the mechanism underlying the regulation of AhR expression in osteoclasts and the signaling pathway through which AhR controls osteoclastogenesis remain unclear. We found that the expression of AhR in bone marrow-derived osteoclasts was upregulated by RANKL at an earlier stage than was the expression of signature osteoclast genes such as those encoding cathepsin K and NFAT, cytoplasmic, calcineurin-dependent 1...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27769811/aryl-hydrocarbon-receptor-ligands-in-cigarette-smoke-induce-production-of-interleukin-22-to-promote-pancreatic-fibrosis-in-models-of-chronic-pancreatitis
#10
Jing Xue, Qinglan Zhao, Vishal Sharma, Linh P Nguyen, Yvonne N Lee, Kim L Pham, Mouad Edderkaoui, Stephen J Pandol, Walter Park, Aida Habtezion
BACKGROUND & AIMS: Cigarette smoke has been identified as an independent risk factor for chronic pancreatitis (CP). Little is known about the mechanisms by which smoking promotes development of CP. We assessed the effects of aryl hydrocarbon receptor (AhR) ligands found in cigarette smoke on immune cell activation in humans and pancreatic fibrosis in animal models of CP. METHODS: We obtained serum samples from patients with CP treated at Stanford University hospital and healthy individuals (controls) and isolated CD4(+) T cells...
December 2016: Gastroenterology
https://www.readbyqxmd.com/read/27728767/dihydromethysticin-dhm-blocks-tobacco-carcinogen-4-methylnitrosamino-1-3-pyridyl-1-butanone-nnk-induced-o-6-methylguanine-in-a-manner-independent-of-the-aryl-hydrocarbon-receptor-ahr-pathway-in-c57bl-6-female-mice
#11
Sreekanth C Narayanapillai, Shang-Hsuan Lin, Pablo Leitzman, Pramod Upadhyaya, Carolyn J Baglole, Chengguo Xing
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a key carcinogen responsible for tobacco smoke-induced lung carcinogenesis. Among the types of DNA damage caused by NNK and its metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), O(6)-methylguanine (O(6)-mG) is likely the most carcinogen in A/J mice. Results of our previous studies showed that levels of O(6)-mG and other types of NNAL-derived DNA damage were preferentially reduced in the lung of female A/J mice upon dietary treatment with dihydromethysticin (DHM), a promising lung cancer chemopreventive agent from kava...
November 21, 2016: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/27598741/a-promoter-variant-within-the-aryl-hydrocarbon-receptor-gene-is-associated-with-an-epithelial-barrier-defect-in-smokers-with-crohn-s-disease
#12
Matthias Prager, Janine Büttner, Philip Grunert, David Ellinghaus, Carsten Büning
BACKGROUND: Smoking worsens Crohn's disease (CD). The aryl hydrocarbon receptor (AhR) is a transcription factor that mediates the toxicity of dioxinlike chemicals. We hypothesized that AHR variants and smoking influence CD. METHODS: Exon-intron boundaries and coding and promoter regions of AHR gene were sequenced (28 patients with inflammatory bowel disease; 4 healthy controls). Two identified variants (rs7796976 and rs2066853) were studied for an association with intestinal permeability (IP, oral sugar test) in patients with inflammatory bowel disease (stratified according to the smoking status)...
October 2016: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/27589885/paternal-exposure-to-cigarette-smoke-condensate-leads-to-reproductive-sequelae-and-developmental-abnormalities-in-the-offspring-of-mice
#13
Prabagaran Esakky, Deborah A Hansen, Andrea M Drury, Paul Felder, Andrew Cusumano, Kelle H Moley
Paternal smoking is associated with infertility, birth defects and childhood cancers. Our earlier studies using cigarette smoke condensate (CSC) demonstrated several deleterious changes in male germ cells. Here, we hypothesize that chronic paternal exposure to CSC causes molecular and phenotypic changes in the sire and the offspring, respectively. In this mouse study, CSC caused DNA damage and cytotoxicity in testes via accumulation of benzo(a)pyrene (B[a]P) and cotinine. Decreased expression of growth arrest and DNA damage inducible alpha (Gadd45a), aryl hydrocarbon receptor (Ahr), and cyclin-dependent kinase inhibitor 1A (P21) was seen in CSC exposed testes...
October 2016: Reproductive Toxicology
https://www.readbyqxmd.com/read/27576004/ahr2-morpholino-knockdown-reduces-the-toxicity-of-total-particulate-matter-to-zebrafish-embryos
#14
Andrey Massarsky, Audrey J Bone, Wu Dong, David E Hinton, G L Prasad, Richard T Di Giulio
The zebrafish embryo has been proposed as a 'bridge model' to study the effects of cigarette smoke on early development. Previous studies showed that exposure to total particulate matter (TPM) led to adverse effects in developing zebrafish, and suggested that the antioxidant and aryl hydrocarbon receptor (AHR) pathways play important roles. This study investigated the roles of these two pathways in mediating TPM toxicity. The study consisted of four experiments. In experiment I, zebrafish embryos were exposed from 6h post fertilization (hpf) until 96hpf to TPM0...
October 15, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27539901/action-spectrum-of-melanoblast-maturation-and-involvement-of-the-aryl-hydrocarbon-receptor
#15
Motoki Nakamura, Emi Nishida, Akimichi Morita
The aryl hydrocarbon receptor (AHR) mediates melanocyte activation and skin tanning. We hypothesized that the AHR also mediates melanoblast-to-melanocyte maturation. In a cloned cell line, NCCmelb4, derived from mouse neural crest cells, we investigated AHR expression in melanoblasts stimulated by UV irradiation and AHR agonists. We irradiated the cells with UV, ranging from 280 to 380 nm in 10-nm increments, using a multiwavelength irradiation spectral apparatus. Tyrosinase expression significantly increased with bimodal peaks at 310 and 360 nm...
August 2016: Experimental Dermatology
https://www.readbyqxmd.com/read/27452439/dichotomous-effects-of-aryl-hydrocarbon-receptor-ahr-activation-on-human-fetoplacental-endothelial-cell-function
#16
Anna Palatnik, Hong Xin, Emily J Su
INTRODUCTION: Maternal cigarette smoking is associated with elevated fetoplacental vascular resistance and fetal growth restriction (FGR). While studies have demonstrated varying effects of nicotine on blood flow, the role of polycyclic aromatic hydrocarbons (PAHs), abundant toxins in cigarette smoke that cross the placenta, has not been elucidated. We hypothesized that exposure of human fetoplacental endothelial cells (ECs) to the PAH benzo[a]yrene (BaP) would result in up-regulation of cyclooxygenase-2 (PTGS2) and preferential production of vasoconstrictive prostanoids via activation of the aryl hydrocarbon receptor (AHR) pathway...
August 2016: Placenta
https://www.readbyqxmd.com/read/27424142/paternal-smoking-and-germ-cell-death-a-mechanistic-link-to-the-effects-of-cigarette-smoke-on-spermatogenesis-and-possible-long-term-sequelae-in-offspring
#17
Prabagaran Esakky, Kelle H Moley
Paternal exposure to constituents of cigarette smoke (CS) is reportedly associated with infertility, birth defects and childhood cancers even though the mechanism behind this relationship is still unclear. Chronic cigarette smoking by men leads to poor sperm quality and quantity mainly through oxidative stress and also direct assault by CS metabolites. Among several carcinogenic and teratogenic components of cigarette smoke condensate (CSC), polycyclic aromatic hydrocarbons (PAHs) display a preeminent role in accelerating germ cell death via the cytoplasmic transcription factor, aryl hydrocarbon receptor (AHR) that is present across all stages of spermatogenesis...
November 5, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27186143/aryl-hydrocarbon-receptor-antagonism-and-its-role-in-rheumatoid-arthritis
#18
REVIEW
Nam Trung Nguyen, Taisuke Nakahama, Chi Hung Nguyen, Trang Thu Tran, Van Son Le, Hoang Ha Chu, Tadamitsu Kishimoto
Although rheumatoid arthritis (RA) is the most common autoimmune disease, affecting approximately 1% of the population worldwide, its pathogenic mechanisms are poorly understood. Tobacco smoke, an environmental risk factor for RA, contains several ligands of aryl hydrocarbon receptor (Ahr), also known as dioxin receptor. Ahr plays critical roles in the immune system. We previously demonstrated that Ahr in helper T-cells contributes to development of collagen-induced arthritis, a mouse model of RA. Other studies have shown that cigarette smoke condensate and pure Ahr ligands exacerbate RA by altering bone metabolism and inducing proinflammatory responses in fibroblast-like synoviocytes...
2015: Journal of Experimental Pharmacology
https://www.readbyqxmd.com/read/27138278/skatole-3-methylindole-is-a-partial-aryl-hydrocarbon-receptor-agonist-and-induces-cyp1a1-2-and-cyp1b1-expression-in-primary-human-hepatocytes
#19
Martin Krøyer Rasmussen, Patrick Balaguer, Bo Ekstrand, Martine Daujat-Chavanieu, Sabine Gerbal-Chaloin
Skatole (3-methylindole) is a product of bacterial fermentation of tryptophan in the intestine. A significant amount of skatole can also be inhaled during cigarette smoking. Skatole is a pulmonary toxin that induces the expression of aryl hydrocarbon receptor (AhR) regulated genes, such as cytochrome P450 1A1 (CYP1A1), in human bronchial cells. The liver has a high metabolic capacity for skatole and is the first organ encountered by the absorbed skatole; however, the effect of skatole in the liver is unknown...
2016: PloS One
https://www.readbyqxmd.com/read/27129092/benzopyrene-a-major-polyaromatic-hydrocarbon-in-smoke-fume-mobilizes-langerhans-cells-and-polarizes-th2-17-responses-in-epicutaneous-protein-sensitization-through-the-aryl-hydrocarbon-receptor
#20
Chien-Hui Hong, Chih-Hung Lee, Hsin-Su Yu, Shau-Ku Huang
BACKGROUND: Atopic dermatitis (AD) is a common disease with genetic and environmental interactions. We previously reported lifetime exposure to cigarette smoke is associated with adult-onset AD. Aryl hydrocarbon receptor (AhR) is important in regulating environmental exposure to xenobiotics, including benzopyrenes (BP), a major polycyclic aromatic hydrocarbon (PAH) present in cigarette smoke. However, how AhR regulates immune responses in sensitization phase of AD remained elusive. METHODS: We investigated how BP affects epicutaneous sensitization response through AhR axis...
July 2016: International Immunopharmacology
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