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https://www.readbyqxmd.com/read/28336214/indoleamine-2-3-dioxygenase-1-ido1-inhibitors-activate-the-aryl-hydrocarbon-receptor
#1
Benjamin J Moyer, Itzel Y Rojas, Iain A Murray, Seokwon Lee, Haley F Hazlett, Gary H Perdew, Craig R Tomlinson
Indoleamine 2,3-dioxygenase 1 (IDO1) plays a key role in the immune system by regulating tryptophan levels and T cell differentiation. Several tumor types overexpress IDO1 to avoid immune surveillance making IDO1 of interest as a target for therapeutic intervention. As a result, several IDO1 inhibitors are currently being tested in clinical trials for cancer treatment as well as several other diseases. Many of the IDO1 inhibitors in clinical trials naturally bear structural similarities to the IDO1 substrate tryptophan, as such, they fulfill many of the structural and functional criteria as potential AHR ligands...
March 20, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28334509/disturbed-testicular-expression-of-the-estrogen-metabolizing-enzymes-cyp1a1-and-comt-in-infertile-men-with-primary-spermatogenic-failure-possible-negative-implications-on-sertoli-cells
#2
A Parada-Bustamante, C Molina, C Valencia, M Flórez, M C Lardone, F Argandoña, A Piottante, M Ebensperguer, P A Orihuela, A Castro
Estradiol (E2 ) is normally metabolized to hydroxyestradiols and methoxyestradiols by CYP1A1, CYP1B1 and COMT. However, an altered production of these metabolites by a disturbed expression of these enzymes is associated with reproductive and non-reproductive pathologies. In vitro studies suggest that increased hydroxyestradiols and methoxyestradiols intratesticular generation is related to male infertility, but no studies have explored whether infertile men have a disturbed testicular expression of the enzymes that generate these E2 metabolites...
March 23, 2017: Andrology
https://www.readbyqxmd.com/read/28316274/co-treatment-with-indole-3-carbinol-and-resveratrol-modify-porcine-cyp1a-and-cyp3a-activities-and-expression
#3
Galia Zamaratskaia, Rebekka Thøgersen, Marjeta Čandek-Potokar, Martin Krøyer Rasmussen
1. Humans and animals are commonly exposed to indole-3-carbinol (I3C) and resveratrol (RES) via food or beverages. Moreover, these compounds have been demonstrated to potentially cause food-drug interactions. However, information about their combined effects is limited. Therefore, we investigated the effects of I3C and RES, both as single compounds and in combination, on cytochrome P450 1A and 3A activity and gene expression. 2. Using porcine microsomes, we demonstrated that RES caused non-competitive inhibition of CYP1A activity and un-competitive inhibition of CYP3A activity...
March 19, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28314282/comparison-of-the-effects-of-monastrol-and-oxomonastrol-on-human-hepatoma-cell-line-hepg2-c3a
#4
Lilian Areal Marques, Simone Cristine Semprebon, Daniele Sartori, Ângelo DE Fátima, Lúcia Regina Ribeiro, Mário Sérgio Mantovani
Monastrol and its analog oxomonastrol differ by replacement of the sulfur atom present in monastrol to an oxygen atom in oxomonastrol. Monastrol inhibits the mitotic kinesin family member 11 (EG5), which has been studied for its potential use in cancer therapy. The aim of this study was to investigate the effect of monastrol and oxomonastrol on HepG2/C3A cells. Our results showed that monastrol induced DNA damage, reduced cell proliferation, and up-regulated the cytochrome P450 family 1 subfamily A member 1 (CYP1A1) mRNA levels...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28300467/association-of-cyp1a1-and-cyp1b1-polymorphisms-with-bone-mineral-density-variations-in-postmenopausal-mexican-mestizo-women
#5
Bertha Chávez, Felipe Vilchis, David Rojano-Mejía, Ramón Mauricio Coral Vázquez, María Del Carmen Aguirre-García, Patricia Canto
Herein, we investigated potential associations between polymorphisms of genes related to estrogen metabolism and bone mineral density (BMD) in postmenopausal women. This was a cross-sectional study, in which two hundred and ninety postmenopausal Mexican-Mestizo women were studied. The BMD of the lumbar spine (LS), total hip (TH), and femoral neck (FN) was measured. The distribution of the genetic polymorphisms, including rs1799814 and rs1048943 at CYP1A1 as well as rs1056836 at CYP1B1, were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), single-stranded conformational polymorphism (SSCP), and DNA sequencing...
March 16, 2017: Gynecological Endocrinology
https://www.readbyqxmd.com/read/28298240/interstrain-differences-in-the-expression-and-activity-of-cyp2a5-in-the-mouse-liver
#6
Katia S Poça, Thiago E M Parente, Lucas F Chagas, Bruna S Leal, Hellen S Leal, Francisco J R Paumgartten, Ana C A X De-Oliveira
BACKGROUND: Cytochrome P450 2A5 (Cyp2a5), a mouse enzyme orthologous of human CYP2A6, catalyzes a number of toxicologically important reactions, including the metabolism of nicotine, aflatoxin B1, and several other xeno- and endobiotics. Cyp2a5 expression is complex and not yet fully understood. We investigated inter-strain differences in the activity and mRNA expression of hepatic Cyp2a5. Cyp1a1/2 and Cyp2b9/10 activities were evaluated for comparative purposes. Data on the interstrain differences in the expression and activity of Cyp2a5 are important to select a suitable mouse model for studying CYP2A6-mediated metabolism...
March 15, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28289825/the-highly-bioactive-molecule-and-signal-substance-6-formylindolo-3-2-b-carbazole-ficz-plays-bi-functional-roles-in-cell-growth-and-apoptosis-in-vitro
#7
Afshin Mohammadi-Bardbori, Farzaneh Bastan, Amin-Reza Akbarizadeh
The maintenance of cellular homeostasis is a complex process that is governed by the receipt of prototypical growth and death signals. The endogenous functions of aryl hydrocarbon receptor (AHR) in cellular homeostasis are not well understood. We aimed to establish whether the disturbance of endogenously activated AHR can influence cell growth, and if so, what mechanism(s) are involved. Cell growth was measured in mouse hepatoma Hepa-1 wild-type and cytochrome P4501A1 (CYP1A1)-deficient c37 cells. In other sets of experiments, HepG2 cells were exposed to different doses of FICZ (0...
March 13, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28289590/susceptibility-to-oral-squamous-cell-carcinoma-correlation-with-variants-of-cyp1a1-mspi-gstt1-gstm1-aldh2-ec-sod-and-lifestyle-factors
#8
T-T Dong, L-J Wang, L-Z Liu, S-N Ma
In order to investigate the association between polymorphisms in genes encoding metabolizing enzymes (CYP1A1-MspI, EC-SOD (extracellular superoxide dismutase), GSTT1, GSTM1, ALDH2), cigarette and alcohol consumption, and the risk of oral squamous cell carcinoma, we conducted a prospective case-control study comprised of 750 individuals with oral squamous cell carcinoma (OSCC) and 750 healthy individuals. Data about smoking and drinking habits were collected along with other demographic and clinical information...
December 1, 2016: Balkan Journal of Medical Genetics: BJMG
https://www.readbyqxmd.com/read/28285566/involvement-of-the-cytokine-ido1-ahr-loop-in-zinc-oxide-nanoparticle-induced-acute-pulmonary-inflammation
#9
Chia-Chi Ho, Hui-Ling Lee, Chao-Yu Chen, Yueh-Hsia Luo, Ming-Hsien Tsai, Hui-Ti Tsai, Pinpin Lin
Zinc oxide nanoparticles (ZnONPs) are widely used in our daily life, such as in sunscreens and electronic nanodevices. However, pulmonary exposure to ZnONPs causes acute pulmonary inflammation, which is considered as an initial event for various respiratory diseases. Thus, elucidation of the underlying cellular mechanisms of ZnONPs can help us in predicting their potential effects in respiratory diseases. In this study, we observed that ZnONPs increased proinflammatory cytokines, accompanied with an increased expression of aryl hydrocarbon receptor (AhR) and its downstream target cytochrome P450 1A1 (CYP1A1) in macrophages in vitro and in mouse lung epithelia in vivo...
March 13, 2017: Nanotoxicology
https://www.readbyqxmd.com/read/28283091/cyp1a1-i462v-polymorphism-is-associated-with-reduced-genotoxicity-in-yeast-despite-positive-association-with-increased-cancer-risk
#10
Julian Freedland, Cinzia Cera, Michael Fasullo
CYP1A1 functions in detoxifying xenobiotics but occasionally converts compounds into potent genotoxins. CYP1A1 activates polyaromatic hydrocarbons, such as benzo[a]pyrene 7,8 dihydrodiol (BaP-DHD), rendering them genotoxic. Particular alleles of CYP1A1, such as CYP1A1 I462V have been correlated with a higher incidence of breast and lung cancer, but it is unknown whether these variants express enzymes in vivo that are more potent in generating genotoxins. We individually expressed CYP1A1 (CYP1A1.1), CYP1A1 T461N (CYP1A1...
March 2017: Mutation Research
https://www.readbyqxmd.com/read/28279696/hydroxystilbenes-and-methoxystilbenes-activate-human-aryl-hydrocarbon-receptor-and-induce-cyp1a-genes-in-human-hepatoma-cells-and-human-hepatocytes
#11
Barbora Pastorková, Aneta Vrzalová, Petr Bachleda, Zdeněk Dvořák
Natural polyphenol resveratrol (trihydroxystilbene) is a partial agonist of human aryl hydrocarbon receptor AhR, thereby, displaying a plethora of biological effects. Biological activities of metoxylated and hydroxylated stilbenes were studied in the past. The aim of the current study was to describe the effects of 13 different hydroxy- and methoxystilbenes, including their cis/trans isomers on the transcriptional activity of AhR and the expression of CYP1A genes in hepatic cancer cells HepG2 and in primary human hepatocytes...
March 6, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28273931/dietary-flavonoids-cyp1a1-genetic-variants-and-the-risk-of-colorectal-cancer-in-a-korean-population
#12
Young Ae Cho, Jeonghee Lee, Jae Hwan Oh, Hee Jin Chang, Dae Kyung Sohn, Aesun Shin, Jeongseon Kim
The role of dietary flavonoid intake in colorectal carcinogenesis might differ according to flavonoid subclasses and individual genetic variants related to carcinogen metabolism. Therefore, we examined whether greater dietary intake of flavonoid subclasses was associated with a lower risk of colorectal cancer and whether CYP1A1 genetic variants altered this association. A semi-quantitative food frequency questionnaire was used to assess the dietary intake of six flavonoid subclasses (flavonols, flavones, flavanones, flavan-3-ols, anthocyanidins, and isoflavones) in 923 patients with colorectal cancer and 1,846 controls; furthermore, CYP1A1 genetic variants (rs4646903 and rs1048943) were genotyped...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28264691/endothelial-responses-of-the-alveolar-barrier-in-vitro-in-a-dose-controlled-exposure-to-diesel-exhaust-particulate-matter
#13
Sebastian G Klein, Sébastien Cambier, Jennifer Hennen, Sylvain Legay, Tommaso Serchi, Inge Nelissen, Aline Chary, Elisa Moschini, Andreas Krein, Brunhilde Blömeke, Arno C Gutleb
BACKGROUND: During the last 250 years, the level of exposure to combustion-derived particles raised dramatically in western countries, leading to increased particle loads in the ambient air. Among the environmental particles, diesel exhaust particulate matter (DEPM) plays a special role because of its omnipresence and reported effects on human health. During recent years, a possible link between air pollution and the progression of atherosclerosis is recognized. A central effect of DEPM is their impact on the endothelium, especially of the alveolar barrier...
March 6, 2017: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/28263535/exposure-of-rats-to-exogenous-endocrine-disruptors-17alpha-ethinylestradiol-and-benzo-a-pyrene-and-an-estrogenic-hormone-estradiol-induces-expression-of-cytochromes-p450-involved-in-their-metabolism
#14
Lucie Borek-Dohalska, Zuzana Klusonova, Jana Holecova, Marketa Martinkova, Frantisek Barta, Helena Dracinska, Tomas Cajthaml, Marie Stiborova
OBJECTIVES: The term "endocrine disruptor" (ED) is used for compounds that mimic or antagonize the effects of endogenous hormones. Synthetic estrogen 17α-ethinylestradiol (EE2) and a human carcinogen benzo[a]pyrene (BaP) are assigned as exogenous endocrine disruptors and an estrogenic hormone estradiol is a natural endogenous disruptor. Here, the potency of these three disruptors administered to rats individually and in combination to induce expression of cytochrome P450 (CYP) enzymes involved in their own metabolism (CYP1A1, 2C and 3A) in vivo was investigated...
December 18, 2016: Neuro Endocrinology Letters
https://www.readbyqxmd.com/read/28259840/quinazoline-derivatives-as-selective-cyp1b1-inhibitors
#15
Mohd Usman Mohd Siddique, Glen J P McCann, Vinay R Sonawane, Neill Horley, Linda Gatchie, Prashant Joshi, Sandip B Bharate, Venkatesan Jayaprakash, Barij N Sinha, Bhabatosh Chaudhuri
CYP1B1 is implicated to have a role in the development of breast, ovarian, renal, skin and lung carcinomas. It has been suggested that identification of potent and specific CYP1B1 inhibitors can lead to a novel treatment of cancer. Flavonoids have a compact rigid skeleton which fit precisely within the binding cavity of CYP1B1. Systematic isosteric replacement of flavonoid 'O' atom with 'N' atom led to the prediction that a 'quinazoline' scaffold could be the basis for designing potential CYP1B1 inhibitors...
April 21, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28254546/relb-attenuates-cigarette-smoke-extract-induced-apoptosis-in-association-with-transcriptional-regulation-of-the-aryl-hydrocarbon-receptor
#16
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/28254063/bioaccumulation-and-the-expression-of-hepatic-cytochrome-p450-genes-in-marine-medaka-oryzias-melastigma-exposed-to-difenoconazole
#17
Lemeng Zhang, Xiaocui Dong, Chonggang Wang, Zhenghong Zuo, Meng Chen
This study was conducted to assess the effects of difenoconazole (DFZ), a triazole fungicide, on the hepatic biotransformation system and its bioaccumulation in marine medaka (Oryzias melastigma). Fish were exposed to DFZ (1, 10, 100, 1000ng/L) for 180days. The results showed that: (1) The mRNA levels of hepatic CYP1A1, CYP1B, CYP1C1, CYP27B and CYP3A40 were up-regulated, but those of CYP3A38 and CYP27A1 were down-regulated. (2) The activity of ethoxyresorufin-O-deethylase (EROD) and the content of reduced glutathione (GSH) in the liver were increased in the DFZ-treated groups, and glutathione S-transferase (GST) activity was increased in the 100 and 1000ng/L groups...
February 2017: Journal of Environmental Sciences (China)
https://www.readbyqxmd.com/read/28250275/optimization-of-albumin-secretion-and-metabolic-activity-of-cytochrome-p450-1a1-of-human-hepatoblastoma-hepg2-cells-in-multicellular-spheroids-by-controlling-spheroid-size
#18
Tomoko Nishikawa, Yutaro Tanaka, Makiya Nishikawa, Yuka Ogino, Kosuke Kusamori, Narumi Mizuno, Yuya Mizukami, Kazunori Shimizu, Satoshi Konishi, Yuki Takahashi, Yoshinobu Takakura
Multicellular spheroids are useful as three-dimensional cell culture systems and for cell-based therapies. Their successful application requires an understanding of the consequences of spheroid size for cellular functions. In the present study, we prepared multicellular spheroids of different sizes using the human hepatoblastoma HepG2 cells, as hepatocytes are frequently used for in vitro drug screening and cell-based therapy. Precise polydimethylsiloxane-based microwells with widths of 360, 450, 560, and 770 µm were fabricated using a micromolding technique...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28247504/epigallocatechin-3-gallate-augments-the-therapeutic-effects-of-benzo-a-pyrene-mediated-lung-carcinogenesis
#19
Meghan M Cromie, Zhongwei Liu, Weimin Gao
Our previous study found curcumin and vitamin E to have protective effects against benzo[a]pyrene (BaP) exposure in human normal lung epithelial BEAS-2B cells. The first objective of this study was to determine whether epigallocatechin-3-gallate (EGCG) elicited the same response. Co-treatment with 5 µM BaP and 20 µM EGCG in BEAS-2B promoted a significant reduction in cell viability and greater G2/M cell cycle arrest, induction of ROS, and reductions in BaP-induced CYP1A1/CYP1B1/COMT, EGFR, p-Akt (Ser473), p-p53 (Thr55), and survivin mRNA/protein expression, as well as an increase in p-p53 (Ser15)...
March 1, 2017: BioFactors
https://www.readbyqxmd.com/read/28245756/diosmetin-induces-cell-apoptosis-by-regulating-cyp1a1-cyp1a2-due-to-p53-activation-in-hepg2-cells
#20
Bin Liu, Kaiqiao Jia, Yu Yang, Siyuan Hao, Caijie Lu, Fengming Xu, Dehui Feng, Runzhi Zhu
It was explored that CYP1 family of cytochromes P450 were over-expressed in several types of cancer. Our study aimed to characterize anti-proliferative activity and metabolism of the natural flavonoid diosmetin in the human hepatoma cell HepG2, expressing CYP1 family. Dios-induced cell apoptosis could be reversed due to p53 blockade and the cellular P53 and CYP1A1/CYP1A2 proteins levels were examined. P53 and CYP1A1/CYP1A2 proteins were up-regulated by Dios; when PFT-α was added into cells, the P53 levels were down-regulated accompanied with up-regulated CYP1A1/CYP1A2...
February 27, 2017: Protein and Peptide Letters
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