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https://www.readbyqxmd.com/read/29324662/aryl-hydrocarbon-receptor-antagonists-mitigate-the-effects-of-dioxin-on-critical-cellular-functions-in-differentiating-human-osteoblast-like-cells
#1
Chawon Yun, Karina M Katchko, Michael S Schallmo, Soyeon Jeong, Jonghwa Yun, Charlotte H Chen, Joseph A Weiner, Christian Park, Andrew George, Samuel I Stupp, Wellington K Hsu, Erin L Hsu
The inhibition of bone healing in humans is a well-established effect associated with cigarette smoking, but the underlying mechanisms are still unclear. Recent work using animal cell lines have implicated the aryl hydrocarbon receptor (AhR) as a mediator of the anti-osteogenic effects of cigarette smoke, but the complexity of cigarette smoke mixtures makes understanding the mechanisms of action a major challenge. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD, dioxin) is a high-affinity AhR ligand that is frequently used to investigate biological processes impacted by AhR activation...
January 11, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29320557/high-ahr-expression-in-breast-tumors-correlates-with-expression-of-genes-from-several-signaling-pathways-namely-inflammation-and-endogenous-tryptophan-metabolism
#2
Sophie Vacher, Patrice Castagnet, Walid Chemlali, François Lallemand, Didier Meseure, Marc Pocard, Ivan Bieche, Martine Perrot-Applanat
Increasing epidemiological and animal experimental data provide substantial support for the role of aryl hydrocarbon receptor (AhR) in mammary tumorigenesis. The effects of AhR have been clearly demonstrated in rodent models of breast carcinogenesis and in several established human breast cancer cell lines following exposure to AhR ligands or AhR overexpression. However, relatively little is known about the role of AhR in human breast cancers. AhR has always been considered to be a regulator of toxic and carcinogenic responses to environmental contaminants such as TCDD (dioxin) and benzo[a]pyrene (BaP)...
2018: PloS One
https://www.readbyqxmd.com/read/29317249/mechanisms-of-2-3-7-8-tetrachlorodibenzo-p-dioxin-induced-cardiovascular-toxicity-an-overview
#3
REVIEW
Mahdieh Sadat Mohsenzadeh, Bamdad Riahi Zanjani, Gholamreza Karimi
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant and its toxicity is mediated by the aryl hydrocarbon receptor (AHR). Mechanisms of TCDD cardiovascular toxicity consist of oxidative stress, growth factor modulation, and ionic current alteration. It is indicated that the rodent cardiovascular system is a target for TCDD cardiomyopathy. Here, our understanding of TCDD cardiovascular toxicity is reviewed.
January 6, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29311254/genetic-and-environmental-effects-on-gene-expression-signatures-of-blood-pressure-a-transcriptome-wide-twin-study
#4
Yisong Huang, Miina Ollikainen, Pyry Sipilä, Linda Mustelin, Xin Wang, Shaoyong Su, Tianxiao Huan, Daniel Levy, James Wilson, Harold Snieder, Jaakko Kaprio, Xiaoling Wang
Recently, 2 transcriptome-wide studies identified 40 genes that were differentially expressed in relation to blood pressure. However, to what extent these BP-related gene expression signatures and their associations with BP are driven by genetic or environmental factors has not been investigated. In this study of 391 twins (193 twin pairs and 5 singletons; age 55-69 years; 40% male; 57% monozygous) recruited from the Finnish Twin Cohort, transcriptome-wide data on peripheral leukocytes were obtained using the Illumina HT12 V4 array...
January 8, 2018: Hypertension
https://www.readbyqxmd.com/read/29301444/the-search-of-car-ahr-esrs-binding-sites-in-promoters-of-intronic-and-intergenic-micrornas
#5
Vladimir Y Ovchinnikov, Denis V Antonets, Lyudmila F Gulyaeva
MicroRNAs (miRNAs) play important roles in the regulation of gene expression at the post-transcriptional level. Many exogenous compounds or xenobiotics may affect microRNA expression. It is a well-established fact that xenobiotics with planar structure like TCDD, benzo(a)pyrene (BP) can bind aryl hydrocarbon receptor (AhR) followed by its nuclear translocation and transcriptional activation of target genes. Another chemically diverse group of xenobiotics including phenobarbital, DDT, can activate the nuclear receptor CAR and in some cases estrogen receptors ESR1 and ESR2...
December 10, 2017: Journal of Bioinformatics and Computational Biology
https://www.readbyqxmd.com/read/29298861/hypersensitive-assessment-of-aryl-hydrocarbon-receptor-transcriptional-activity-using-a-novel-truncated-cyp1a-promoter-in-zebrafish
#6
Juan-Juan Luo, Dong-Sheng Su, Shao-Lin Xie, Yi Liu, Pei Liu, Xiao-Jun Yang, De-Sheng Pei
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent organic pollutant (POP), an unintentional byproduct of various industrial processes, and a human carcinogen. The expression of the cytochrome P450 1A (cyp1a) gene is upregulated in the presence of TCDD through activating the aryl hydrocarbon receptor pathway in a dose-dependent manner. Several essential response elements, including the 8 potential xenobiotic response elements in the cyp1a promoter region, have been identified to be the main functional parts for the response to TCDD...
January 3, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29289296/identification-of-differentially-expressed-genes-response-to-tcdd-in-rat-brain-after-long-term-low-dose-exposure
#7
Yangsheng Chen, Li Xu, Heidi Q H Xie, Tuan Xu, Hualing Fu, Songyan Zhang, Rui Sha, Yingjie Xia, Bin Zhao
Several cohort studies have reported that dioxin and dioxin-like polychlorinated biphenyls might impair the nervous system and lead to neurological or neurodegenerative diseases in the elder people, but there is limited research on the involved mechanism. By using microarray analysis, we figured out the differentially expressed genes between brain samples from SD rats after low-dose (0.1μg/(kg▪bw)) dioxin exposure for six months and controls. To investigate the function changes in the course of dioxin exposure, Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the differentially expressed genes...
December 2017: Journal of Environmental Sciences (China)
https://www.readbyqxmd.com/read/29287180/neurocognitive-and-physical-functioning-in-the-seveso-women-s-health-study
#8
Jennifer Ames, Marcella Warner, Paolo Brambilla, Paolo Mocarelli, William A Satariano, Brenda Eskenazi
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is neurotoxic in animals but few studies have investigated its effects on the human brain. Related dioxin-like compounds have been linked to poorer cognitive and motor function in older adults, with effects more pronounced in women, perhaps due to the loss of neuro-protective estrogen in menopause. On 10 July 1976, a chemical explosion in Seveso, Italy, resulted in one of the highest known residential exposures to TCDD. In 1996, we initiated the Seveso Women's Health Study, a retrospective cohort study of the health of the women who were newborn to 40 years old in 1976...
December 26, 2017: Environmental Research
https://www.readbyqxmd.com/read/29274782/the-aryl-hydrocarbon-receptor-regulates-the-expression-of-tiparp-and-its-cis-long-non-coding-rna-tiparp-as1
#9
Giulia Grimaldi, Sharanya Rajendra, Jason Matthews
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor and member of the basic helix-loop-helix-PAS family. AHR is activated by numerous dietary and endogenous compounds that contribute to its regulation of genes in diverse signaling pathways including xenobiotic metabolism, vascular development, immune responses and cell cycle control. However, it is most widely studied for its role in mediating 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity. The AHR target gene and mono-ADP-ribosyltransferase, TCDD-inducible poly-ADP-ribose polymerase (TIPARP), was recently shown to be part of a novel negative feedback loop regulating AHR activity through mono-ADP-ribosylation...
December 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29249152/age-corrected-trends-and-toxic-equivalence-of-pcdd-f-and-cp-pcbs-in-lake-trout-and-walleye-from-the-great-lakes-2004-2014
#10
James J Pagano, Andrew J Garner, Daryl McGoldrick, Bernard S Crimmins, Philip K Hopke, Michael S Milligan, Thomas M Holsen
Our research reports lake trout and walleye polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and co-planar polychlorinated biphenyls (CP-PCBs) concentrations and age-corrected trends in the Great Lakes over the 2004-2014 period. We determined that age-contaminant corrections are required to accurately report contaminant trends due to significant lake trout age structure changes. The age-trend model (ATM) described here uses a lake-specific age-contaminant regression to mitigate the effect of a fluctuating lake trout age structure to directly improve the log-linear regression model...
December 16, 2017: Environmental Science & Technology
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
#11
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/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
#12
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
https://www.readbyqxmd.com/read/29165700/epigenetic-therapy-novel-translational-implications-for-arrest-of-environmental-dioxin-induced-disease-in-females
#13
Zaraq Khan, Ye Zheng, Tiffanny L Jones, Abigail A Delaney, Luiz F Correa, Chandra C Shenoy, Khashayarsha Khazaie, Gaurang S Daftary
Increased toxicant exposure and resultant environmentally-induced diseases are a tradeoff of industrial productivity. Dioxin (TCDD: 2,3,7,8 tetrachlorodibenzo-p-dioxin), a ubiquitous by-product is associated with a spectrum of diseases including endometriosis, a common, chronic disease in women. TCDD activates cytochrome p450 (CYP) metabolic enzymes, which alters organ function to cause disease. In contrast, the transcription factor, Krüppel-Like Factor (KLF) 11 represses these enzymes via epigenetic mechanisms...
November 17, 2017: Endocrinology
https://www.readbyqxmd.com/read/29154098/generation-and-application-of-a-novel-transgenic-zebrafish-line-tg-cyp1a-mcherry-as-an-in-vivo-assay-to-sensitively-monitor-pahs-and-tcdd-in-the-environment
#14
Shao-Lin Xie, Muhammad Junaid, Wan-Ping Bian, Juan-Juan Luo, Jabir Hussain Syed, Chao Wang, Wen-Xu Xiong, Yan-Bo Ma, Aping Niu, Xiao-Jun Yang, Ji-Xing Zou, De-Sheng Pei
The polycyclic aromatic hydrocarbons (PAHs) and 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) are classified as human carcinogens, and can also cause serious health problems. To develop a convenient bio-monitoring tool for the detection of PAHs and TCDD in the environment, we generated a transgenic zebrafish line Tg(cyp1a:mCherry) with cyp1a promoter driving mCherry expression. Here, Tg(cyp1a:mCherry) embryos were treated with different concentrations of TCDD and five US EPA priority PAHs congeners. The results showed that the expressions of mCherry and endogenous cyp1a were consistent with the PAHs exposure concentrations and were largely induced by TCDD and ≥4-ring PAHs...
November 13, 2017: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/29153057/sex-dependent-influence-of-developmental-toxicant-exposure-on-group-b-streptococcus-mediated-preterm-birth-in-a-murine-model
#15
Tianbing Ding, Lauren A Lambert, David M Aronoff, Kevin G Osteen, Kaylon L Bruner-Tran
Infectious agents are a significant risk factor for preterm birth (PTB); however, the simple presence of bacteria is not sufficient to induce PTB in most women. Human and animal data suggest that environmental toxicant exposures may act in concert with other risk factors to promote PTB. Supporting this "second hit" hypothesis, we previously demonstrated exposure of fetal mice (F1 animals) to the environmental endocrine disruptor 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) leads to an increased risk of spontaneous and infection-mediated PTB in adult animals...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/29136567/persistent-organic-pollutants-in-red-and-white-blooded-high-antarctic-notothenioid-fish-from-the-remote-weddell-sea
#16
Anneli Strobel, Peter Schmid, Patricia Burkhardt-Holm, Helmut Segner, Markus Zennegg
It has been suggested that High-Antarctic waters, despite their remoteness from human activities, are impacted by anthropogenic pollution, and that the local biota are accumulating the contaminants. At present, no data exist on persistent organic pollutant (POP) body burdens for notothenioid fish inhabiting the High-Antarctic Weddell Sea. We determined the pollutant load in white muscle tissue of red- and white-blooded notothenoids from the Weddell Sea (Trematomus loennbergii and Chionodraco hamatus, respectively), and compared them to our previous measurements of POPs in Low-Antarctic notothenioids...
November 7, 2017: Chemosphere
https://www.readbyqxmd.com/read/29109131/carbidopa-a-selective-ah-receptor-modulator-sahrm
#17
Stephen Safe
The aryl hydrocarbon receptor (AhR) was discovered as the intracellular receptor that bound with high affinity to the environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and the AhR is required for mediating the toxicity induced by TCDD. Subsequent studies show that the AhR binds structurally diverse chemicals including plant-derived compounds that promote health and several AhR-active pharmaceuticals that exhibit anticancer activity. In this issue, there is a report that carbidopa, a drug used for treating Parkinson's disease, is also an AhR ligand, and this compound inhibits pancreatic cancer cell and tumor growth...
November 6, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/29107029/transcriptional-inhibition-of-tcdd-mediated-induction-of-cytochrome-p450-1a1-and-alteration-of-protein-expression-in-a-zebrafish-hepatic-cell-line-following-the-administration-of-tcdd-and-cd-2
#18
Ying Ying Chen, King Ming Chan
We studied the effects of Cd(2+) on TCDD-mediated induction of the cytochrome P450 1A1 (cyp1a1) gene using a zebrafish liver cell line (ZFL). Our results showed that Cd(2+) inhibited the TCDD-mediated induction of the cyp1a1 protein, enzyme activity, and mRNA expression level. Cd(2+) also down-regulated levels of the aryl hydrocarbon receptor (ahr2) and the aryl hydrocarbon receptor nuclear translocator 2b (arnt2b) mRNAs. Compared with TCDD (3nM) treatment alone, co-treatment with Cd(2+) (0-30μM) and TCDD (3nM) significantly inhibited the activity of the luciferase reporter gene constructs harboring the distal promoter region (P-2626/-2009) of CYP1A1 and the synthetic 3XRE gene promoter...
October 26, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29093374/-molecular-mechanism-whereby-maternal-exposure-to-dioxin-suppresses-sexual-maturation-of-the-offspring-after-growing-up
#19
Tomoki Takeda
 Dioxins, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), are responsible for producing serious toxic effects in the next generation, such as sexual immaturity. Our laboratory found that treating pregnant rats on gestational day 15 with TCDD (1 μg/kg orally) targets pituitary luteinizing hormone (LH) to attenuate testicular steroidogenesis in fetuses. Because sex steroids during a short window ("the critical period") in the perinatal stage stimulate brain differentiation closely linked to sexual maturation, it is likely that TCDD imprints sexual immaturity on the offspring due to the lowered expression of LH during the fetal period...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/29092071/the-regulation-mechanisms-of-ahr-by-molecular-chaperone-complex
#20
Ikuru Kudo, Miki Hosaka, Asami Haga, Noriko Tsuji, Yuhtaroh Nagata, Hirotaka Okada, Kana Fukuda, Yuka Kakizaki, Tomoya Okamoto, Ewa Grave, Hideaki Itoh
The AhR, so called the dioxin receptor, is a member of the nuclear receptor superfamily. The ligand-free AhR forms a cytosolic protein complex with the molecular chaperone HSP90, co-chaperone p23, and XAP2 in the cytoplasm. Following ligand binding like 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD), the AhR translocates into the nucleus. Although it has been reported that HSP90 regulates the translocation of the AhR to the nucleus, the precise activation mechanisms of the AhR have not yet been fully understood...
October 28, 2017: Journal of Biochemistry
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