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https://www.readbyqxmd.com/read/28634910/the-complex-biology-of-the-aryl-hydrocarbon-receptor-and-its-role-in-the-pituitary-gland
#1
REVIEW
Robert Formosa, Josanne Vassallo
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor best known for its ability to mediate the effects of environmental toxins such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin), polycyclic aromatic hydrocarbons (PAHs), benzene, and polychlorinated biphenyls (PCBs) through the initiation of transcription of a number of metabolically active enzymes. Therefore, the AHR has been studied mostly in the context of xenobiotic signaling. However, several studies have shown that the AHR is constitutively active and plays an important role in general cell physiology, independently of its activity as a xenobiotic receptor and in the absence of exogenous ligands...
June 20, 2017: Hormones & Cancer
https://www.readbyqxmd.com/read/28621812/tcdd-induces-ubch7-expression-and-synphilin-1-protein-degradation-in-the-mouse-ventral-midbrain
#2
Emmanuel González-Barbosa, Alejandro Mejía-García, Elizabeth Bautista, Frank J Gonzalez, José Segovia, Guillermo Elizondo
UbcH7 is an ubiquitin-conjugating enzyme that interacts with parkin, an E3 ligase. The UbcH7-parkin complex promotes the ubiquitination and degradation of several proteins via the 26S proteasome. Cellular accumulation of the UbcH7-parkin targets alpha-synuclein, and synphilin-1 has been associated with Parkinson disease. In mouse liver, 2,3,7,8-tetrachlorodibenzo-p-dioxin, an aryl hydrocarbon receptor ligand, induces UbcH7 expression. Therefore, the aim of the present study was to determine whether 2,3,7,8-tetrachlorodibenzo-p-dioxin induces Ubch7 mRNA and UbcH7 protein expression in the mouse brain, to characterize the molecular mechanism, and the effect on synphilin-1 half-life...
June 16, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28618207/effect-of-dioxin-and-17%C3%AE-estradiol-on-the-expression-of-cytochrome-p450-1a1-gene-via-an-estrogen-receptor-dependent-pathway-in-cellular-and-xenografted-models
#3
Ryeo-Eun Go, Kyung-A Hwang, Cho-Won Kim, Yong-Sub Byun, Ki-Hoan Nam, Kyung-Chul Choi
Cytochrome P450 (CYP) 1A1 plays a major role in the metabolic activation of procarcinogens to carcinogens via aryl hydrocarbon receptor (AhR) pathway. Especially, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is known as an agonist of AhR. In estrogen responsive cancers, 17β-estradiol (E2) may influence on AhR dependent expression of CYP1 family via the interaction between estrogen receptor (ER) and AhR. In the present study, the effect of E2/ER on the expression of AhR and CYP1A1 genes was investigated for MCF-7 clonal variant (MCF-7 CV) breast cancer cells expressing ER...
June 15, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28571685/activation-of-the-aryl-hydrocarbon-receptor-decreases-rifampicin-induced-cyp3a4-expression-in-primary-human-hepatocytes-and-heparg
#4
Martin Krøyer Rasmussen, Martine Daujat-Chavanieu, Sabine Gerbal-Chaloin
The role of the cross-talk between nuclear receptors in the regulation of Cytochrome P450 expression in the liver is well-documented. Most studies have focused on the cross-talk between the pregnane X receptor (PXR) and other receptors, such as the constitutive androstane receptor. However, cross-talk between PXRs and aryl hydrocarbon receptors (AhRs) has also been suggested, but reports regarding this cross-talk are conflicting. In the present study, we treated HepaRG and primary human hepatocytes (PHHs) with both a strong (TCDD) and weak (3-methylindole; 3MI) AhR activator to investigate their impact on PXR-regulated expression of CYP3A4...
May 29, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28552310/separate-screening-of-brominated-and-chlorinated-dioxins-in-field-samples-using-in%C3%A2-vitro-reporter-gene-assays-with-rat-and-mouse-hepatoma-cell-lines
#5
Go Suzuki, Masafumi Nakamura, Chieko Michinaka, Nguyen Minh Tue, Hiroshi Handa, Hidetaka Takigami
In 2011, a joint World Health Organization (WHO) and United Nations Environment Programme expert panel recommended the use of the WHO toxicity equivalency factor (TEF) scheme for assessment of the human health risks of brominated dioxins which have different sources from chlorinated dioxins. Therefore, WHO toxic equivalents (TEQs) should be determined for both chlorinated and brominated dioxins. As alternative to the conventional but time-consuming dioxin analysis using gas chromatography high-resolution mass spectrometry, we have developed a screening method involving cleanup and separation of brominated dioxins from chlorinated dioxins in field samples and subsequent analysis by CALUX (chemically activated luciferase expression) assays which are in vitro reporter gene assays detecting dioxin-like compounds...
July 4, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28536482/nad-loss-a-new-player-in-ahr-biology-prevention-of-thymus-atrophy-and-hepatosteatosis-by-nad-repletion
#6
Silvia Diani-Moore, Jenny Shoots, Rubi Singh, Joshua B Zuk, Arleen B Rifkind
Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) is a carcinogenic and highly toxic industrial byproduct that persists in the environment and produces a pleiotropic toxicity syndrome across vertebrate species that includes wasting, hepatosteatosis, and thymus atrophy. Dioxin toxicities require binding and activation of the aryl hydrocarbon receptor (AhR), a ligand activated transcription factor. However, after nearly 50 years of study, it remains unknown how AhR activation by dioxin produces toxic effects...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28533309/aryl-hydrocarbon-receptor-inhibition-promotes-hemato-lymphoid-development-from-human-pluripotent-stem-cells
#7
Mathew G Angelos, Paige N Ruh, Beau R Webber, Robert H Blum, Caitlin D Ryan, Laura Bendzick, Seonhui Shim, Ashley M Yingst, Dejene M Tufa, Michael R Verneris, Dan S Kaufman
The aryl hydrocarbon receptor (AHR) plays an important physiological role in hematopoiesis. AHR is highly expressed in hematopoietic stem/progenitor cells (HSPCs) and inhibition of AHR results in a marked expansion of human umbilical cord blood-derived HSPCs following cytokine stimulation. It is unknown whether AHR also contributes earlier in human hematopoietic development. To model hematopoiesis, human embryonic stem cells (hESCs) were allowed to differentiate in defined conditions in the presence of the AHR antagonist StemReginin-1 (SR-1) or AHR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)...
May 22, 2017: Blood
https://www.readbyqxmd.com/read/28523069/crosstalk-between-aryl-hydrocarbon-receptor-and-glucocorticoid-receptor-in-human-retinal-pigment-epithelial-cells
#8
Hong Lan Jin, Yujin Choi, Kwang Won Jeong
The aryl hydrocarbon receptor (AHR) is known to mediate the cellular reaction involved in processing environmental contaminants and, ultimately, preventing accumulation of unfavorable extra lipids and proteins. Glucocorticoid receptor (GR) mediates the expression of genes associated with anti-inflammatory properties. Because AHR and GR are closely related in lipid metabolic dysregulation and inflammation, we speculate that AHR and GR may play a crucial role in AMD pathogenesis and focus on their crosstalk in human retinal pigment epithelial cells (ARPE-19)...
2017: International Journal of Endocrinology
https://www.readbyqxmd.com/read/28508231/role-of-the-aryl-hydrocarbon-receptor-in-carcinogenesis-and-potential-as-an-anti-cancer-drug-target
#9
REVIEW
Siva Kumar Kolluri, Un-Ho Jin, Stephen Safe
The aryl hydrocarbon receptor (AhR) was initially identified as the receptor that binds and mediates the toxic effects induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and structurally related halogenated aromatics. Other toxic compounds including some polynuclear aromatic hydrocarbons act through the AhR; however, during the last 25 years, it has become apparent that the AhR plays an essential role in maintaining cellular homeostasis. Moreover, the scope of ligands that bind the AhR includes endogenous compounds such as multiple tryptophan metabolites, other endogenous biochemicals, pharmaceuticals and health-promoting phytochemicals including flavonoids, indole-3-carbinol and its metabolites...
May 15, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28498411/mitochondrial-activity-and-oxidative-stress-functions-are-influenced-by-the-activation-of-ahr-induced-cyp1a1-overexpression-in-cardiomyocytes
#10
Bing Zhou, Xi Wang, Feng Li, Yingting Wang, Lei Yang, Xiaolong Zhen, Wuhong Tan
There is an endemic cardiomyopathy currently occurring in China, termed, Keshan disease (KD). The authors previously compared mitochondrial‑associated gene expression profiles of peripheral blood mononuclear cells (PBMCs) derived from KD patients and normal controls, using mitochondria‑focused cDNA microarray technology. The results detected an upregulation of the enzyme‑associated CYP1A1 gene, (ratios ≥2.0). The aryl hydrocarbon receptor (AhR) regulates the expression of numerous cytochrome P450 (CYP) genes including members of the CYP1 family; CYP1A1 and CYP1A2...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28487374/dioxin-induced-increase-in-leukotriene-b4-biosynthesis-through-the-aryl-hydrocarbon-receptor-and-its-relevance-to-hepatotoxicity-owing-to-neutrophil-infiltration
#11
Tomoki Takeda, Yukiko Komiya, Takayuki Koga, Takumi Ishida, Yuji Ishii, Yasushi Kikuta, Michio Nakaya, Hitoshi Kurose, Takehiko Yokomizo, Takao Shimizu, Hiroshi Uchi, Masutaka Furue, Hideyuki Yamada
Dioxin and related chemicals alter the expression of a number of genes by activating the aryl hydrocarbon receptors (AHRs) to produce a variety of disorders including hepatotoxicity. However, it remains largely unknown how these changes in gene expression are linked to toxicity. To address this issue, we initially examined the effect of 2,3,7,8-tetrachrolodibenzo-p-dioxin (TCDD), a most toxic dioxin, on the hepatic and serum metabolome in male pubertal rats. The results obtained showed that TCDD causes many changes in the level of fatty acids, bile acids, amino acids and their metabolites...
May 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28475713/tcdd-influences-reservoir-of-antibiotic-resistance-genes-in-murine-gut-microbiome
#12
Robert D Stedtfeld, Tiffany M Stedtfeld, Kelly A Fader, Maggie R Williams, Prianca Bhaduri, John Quensen, Timothy R Zacharewski, James M Tiedje, Syed A Hashsham
Dysbiosis of the gut microbiome via antibiotics, changes in diet and infection can select for bacterial groups that more frequently harbor antimicrobial resistance genes (ARGs) and mobile genetic elements (MGEs). However, the impact of environmental toxicants on the reservoir of ARGs in the gut microbiome has received less attention. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent aryl hydrocarbon receptor (AhR) agonist with multiple toxic health effects including immune dysfunction. The selective pressure of TCDD on the abundance of ARG and MGE-harboring gut populations was examined using C57BL/6 mice exposed to 0-30 μg/kg TCDD for 28 and 92 days with the latter having a 30-day recovery period...
May 1, 2017: FEMS Microbiology Ecology
https://www.readbyqxmd.com/read/28441827/-colonization-rate-of-clostridium-difficile-in-healthy-children
#13
Y Wang, S Guo, C N Zhao, X W Xu
Objective: To learn the colonization of Clostridium difficile in local healthy children and to investigate the colonization rate and toxin types of Clostridium difficile at different ages. Method: From September 2014 to January 2015 in a case observational study, healthy children's fecal specimens from the health care department of Beijing Children's Hospital were collected. The children were divided into four groups according to age: <1 year old(n=53), 1-<3 years old(n=50), 3-<6 years old(n=50) and 6-<14 years old(n=50) respectively...
April 2, 2017: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
https://www.readbyqxmd.com/read/28433708/toxicological-characterisation-of-two-novel-selective-aryl-hydrocarbon-receptor-modulators-in-sprague-dawley-rats
#14
COMPARATIVE STUDY
Selma Mahiout, Jere Lindén, Javier Esteban, Ismael Sánchez-Pérez, Satu Sankari, Lars Pettersson, Helen Håkansson, Raimo Pohjanvirta
The aryl hydrocarbon receptor (AHR) mediates the toxicity of dioxins, but also plays important physiological roles. Selective AHR modulators, which elicit some effects imparted by this receptor without causing the marked toxicity of dioxins, are presently under intense scrutiny. Two novel such compounds are IMA-08401 (N-acetyl-N-phenyl-4-acetoxy-5-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide) and IMA-07101 (N-acetyl-N-(4-trifluoromethylphenyl)-4-acetoxy-1,2-dihydro-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide)...
July 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28405246/modulation-of-benzo-a-pyrene-dna-adduct-formation-by-cyp1-inducer-and-inhibitor
#15
REVIEW
Kazuhiro Shiizaki, Masanobu Kawanishi, Takashi Yagi
Benzo[a]pyrene (BaP) is a well-studied pro-carcinogen that is metabolically activated by cytochrome P450 enzymes. Cytochrome P4501A1 (CYP1A1) has been considered to play a central role in the activation step, which is essential for the formation of DNA adducts. This enzyme is strongly induced by many different chemical agents, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which binds to the aryl hydrocarbon receptor (AhR). Therefore, AhR activators are suspected to have the potential to aggravate the toxicity of BaP through the induction of CYP1A1...
2017: Genes and Environment: the Official Journal of the Japanese Environmental Mutagen Society
https://www.readbyqxmd.com/read/28386637/2-3-7-8-tetrachlorodibenzo-p-dioxin-tcdd-mediated-deregulation-of-myeloid-and-sebaceous-gland-stem-progenitor-cell-homeostasis
#16
REVIEW
Karl Walter Bock
Studies of TCDD toxicity stimulated identification of the responsible aryl hydrocarbon receptor (AHR), a multifunctional, ligand-activated transcription factor of the basic helix-loop-helix/Per-Arnt-Sim family. Accumulating evidence suggests a role of this receptor in homeostasis of stem/progenitor cells, in addition to its known role in xenobiotic metabolism. (1) Regulation of myelopoiesis is complex. As one example, AHR-mediated downregulation of human CD34+ progenitor differentiation to monocytes/macrophages is discussed...
April 6, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28385905/in-vivo-characterization-of-an-ahr-dependent-long-noncoding-rna-required-for-proper-sox9b-expression
#17
Gloria R Garcia, Britton C Goodale, Michelle W Wiley, Jane K La Du, David A Hendrix, Robert L Tanguay
Xenobiotic activation of the aryl hydrocarbon receptor (AHR) by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) prevents the proper formation of craniofacial cartilage and the heart in developing zebrafish. Downstream molecular targets responsible for AHR-dependent adverse effects remain largely unknown; however, in zebrafish sox9b has been identified as one of the most-reduced transcripts in several target organs and is hypothesized to have a causal role in TCDD-induced toxicity. The reduction of sox9b expression in TCDD-exposed zebrafish embryos has been shown to contribute to heart and jaw malformation phenotypes...
June 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28377982/mechanistic-insight-into-the-effects-of-aryl-hydrocarbon-receptor-activation-on-osteogenic-differentiation
#18
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/28370362/sequestration-of-2-3-7-8-tetrachlorodibenzo-p-dioxin-by-activated-carbon-eliminates-bioavailability-and-the-suppression-of-immune-function-in-mice
#19
Stephen A Boyd, J Brett Sallach, Yingjie Zhang, Robert Crawford, Hui Li, Cliff T Johnston, Brian J Teppen, Norbert E Kaminski
The effectiveness of activated carbon in reducing the bioavailability of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was examined from the context of using in situ sorbent amendments to remediate soils/sediments contaminated with polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs). This technology has gained rapid acceptance based on observations that activated carbon amendments predictably lower PCDD/F concentrations in water and bioaccumulation by simple aquatic organisms and earthworms; it has been assumed that bioavailability to mammals is similarly reduced, although this has been disproven for other sorbent materials...
April 1, 2017: Environmental Toxicology and Chemistry
https://www.readbyqxmd.com/read/28341572/cell-and-region-specificity-of-aryl-hydrocarbon-receptor-ahr-system-in-the-testis-and-the-epididymis
#20
A Wajda, J Łapczuk, M Grabowska, E Pius-Sadowska, M Słojewski, M Laszczynska, E Urasinska, B Machalinski, M Drozdzik
Aryl hydrocarbon receptor (AhR) plays multiple important functions in adaptive responses. Exposure to AhR ligands may produce an altered metabolic activity controlled by the AhR pathways, and consequently affect drug/toxin responses, hormonal status and cellular homeostasis. This research revealed species-, cell- and region-specific pattern of the AhR system expression in the rat and human testis and epididymis, complementing the existing knowledge, especially within the epididymal segments. The study showed that AhR level in the rat and human epididymis is higher than in the testis...
March 21, 2017: Reproductive Toxicology
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