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CYP1A1

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https://www.readbyqxmd.com/read/28722335/protective-effects-of-folic-acid-on-pm2-5-induced-cardiac-developmental-toxicity-in-zebrafish-embryos-by-targeting-ahr-and-wnt-%C3%AE-catenin-signal-pathways
#1
Cong Yue, Cheng Ji, Hang Zhang, Leshuai W Zhang, Jian Tong, Yan Jiang, Tao Chen
Our previous observations indicated that extractable organic matter (EOM) from PM2.5 induced malformations in the heart of zebrafish embryos by activating AhR and inhibiting canonical Wnt/β-catenin signal pathway. As a nutritional factor, folic acid (FA) is reported to prevent cardiac defects during embryo development. Hence, we hypothesize that FA may prevent PM2.5-induced heart defects by interfering with AhR and Wnt/β-catenin signaling pathways. Our results showed that FA supplementation alleviated the EOM-induced heart defects in zebrafish embryos, and both AhR inhibitor CH223191 and Wnt activator CHIR99021 enhanced the protective efficiency of FA...
July 19, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28714190/polymorphisms-of-xenobiotic-metabolizing-genes-and-colorectal-cancer-risk-in-patients-with-lynch-syndrome-a-retrospective-cohort-study-in-taiwan
#2
Abram Bunya Kamiza, Jeng-Fu You, Wen-Chang Wang, Reiping Tang, Chun-Yu Chang, Huei-Tzu Chien, Chih-Hsiung Lai, Li-Ling Chiu, Tsai-Ping Lo, Kuan-Yi Hung, Chao A Hsiung, Chih-Ching Yeh
Cytochrome P450 (CYP), glutathione-S-transferase (GST), and N-acetyltransferase (NAT) are crucial for metabolism and clearance of xenobiotics. This study investigated whether CYP, GST, and NAT single nucleotide polymorphisms (SNPs) are associated with colorectal cancer (CRC) in patients with Lynch syndrome. The interaction between these SNPs and cigarette smoking or meat consumption was also explored. We identified 270 patients with Lynch syndrome from the Taiwan Hereditary Nonpolyposis Colorectal Cancer Consortium...
July 17, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28711350/synthesis-and-biological-evaluation-of-pyrrole-based-chalcones-as-cyp1-enzyme-inhibitors-for-possible-prevention-of-cancer-and-overcoming-cisplatin-resistance
#3
Ibidapo S Williams, Prashant Joshi, Linda Gatchie, Mohit Sharma, Naresh K Satti, Ram A Vishwakarma, Bhabatosh Chaudhuri, Sandip B Bharate
Inhibitors of CYP1 enzymes may play vital roles in the prevention of cancer and overcoming chemo-resistance to anticancer drugs. In this letter, we report synthesis of twenty-three pyrrole based heterocyclic chalcones which were screened for inhibition of CYP1 isoforms. Compound 3n potently inhibited CYP1B1 with an IC50 of ∼0.2μM in Sacchrosomes™ and CYP1B1-expressing live human cells. However, compound 3j which inhibited both CYP1A1 and CYP1B1 with an IC50 of ∼0.9µM, using the same systems, also potently antagonized B[a]P-mediated induction of AhR signaling in yeast (IC50, 1...
July 4, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28710019/effects-of-human-blood-levels-of-two-pah-mixtures-on-the-ahr-signalling-activation-pathway-and-cyp1a1-and-comt-target-genes-in-granulosa-non-tumor-and-granulosa-tumor-cell-lines
#4
Karolina Zajda, Anna Ptak, Agnieszka Rak, Elżbieta Fiedor, Adam Grochowalski, Tomasz Milewicz, Ewa L Gregoraszczuk
Epidemiological studies have shown a link between problems with offspring of couples living in a contaminated environment in comparison to those who live in an uncontaminated environment. We measured the concentrations of 16 priority polycyclic aromatic hydrocarbons (PAHs) in maternal and cord blood. To explore the mechanism of the effects of PAH mixtures on nonluteinized granulosa cells (HGrC1) and granulosa tumor cells (COV434), as well as cell proliferation and apoptosis, we investigated the effect of PAH mixtures on the expression of the aryl hydrocarbon receptor (AHR), aryl hydrocarbon receptor nuclear translocator (ARNT) and aryl hydrocarbon receptor repressor (AHRR) genes, as well as the expression and activity of target genes cytochrome P450 1A1 (CYP1A1) and catechol-O-methyltransferase (COMT)...
July 11, 2017: Toxicology
https://www.readbyqxmd.com/read/28703914/hsd3b2-associated-in-modulating-steroid-hormone-synthesis-pathway-regulates-the-differentiation-of-chicken-embryonic-stem-cells-into-spermatogonial-stem-cells
#5
Chen Zhang, Man Wang, Nana He, Mahmoud F Ahmed, Yilin Wang, Ruifeng Zhao, Xinjian Yu, Jing Jin, Jiuzhou Song, Qisheng Zuo, Yani Zhang, Bichun Li
Steroid hormones regulate differentiation of various types of cell during embryogenesis. Testosterone is one of the androgens that bind to receptors to regulate gene expression and promote spermatogenesis. Our results showed that testosterone, as a product of steroid hormones synthesis pathway, could facilitate the differentiation of embryonic stem cells (ESCs) into spermatogonial stem cells (SSCs). The analysis of the steroid hormones synthesis pathway demonstrated that 3beta-hydroxysteroid dehydrogenase2 (Hsd3b2) plays a major role in the synthesis of testosterone...
July 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28699004/a-delayed-proinflammatory-response-of-human-preadipocytes-to-pcb126-is-dependent-on-the-aryl-hydrocarbon-receptor
#6
Francoise A Gourronc, Larry W Robertson, Aloysius J Klingelhutz
Inflammation in adipose tissue is recognized as a causative factor in the development of type II diabetes. Adipocyte hypertrophy as well as bacterial and environmental factors have been implicated in causing inflammation in mature adipocytes. Exposure to persistent organic pollutants such as polychlorinated biphenyls (PCBs) has been associated with the development of type II diabetes. We show here that PCB126, a dioxin-like PCB, activates a robust proinflammatory state in fat cell precursors (preadipocytes)...
July 11, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28698457/review-of-ligand-specificity-factors-for-cyp1a-subfamily-enzymes-from-molecular-modeling-studies-reported-to-date
#7
REVIEW
Jayalakshmi Sridhar, Navneet Goyal, Jiawang Liu, Maryam Foroozesh
The cytochrome P450 (CYP) family 1A enzymes, CYP1A1 and CYP1A2, are two of the most important enzymes implicated in the metabolism of endogenous and exogenous compounds through oxidation. These enzymes are also known to metabolize environmental procarcinogens into carcinogenic species, leading to the advent of several types of cancer. The development of selective inhibitors for these P450 enzymes, mitigating procarcinogenic oxidative effects, has been the focus of many studies in recent years. CYP1A1 is mainly found in extrahepatic tissues while CYP1A2 is the major CYP enzyme in human liver...
July 8, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28696214/epigenetic-regulation-by-agonist-specific-aryl-hydrocarbon-receptor-recruitment-of-metastatic-associated-protein-2-selectively-induces-stanniocalcin-2-expression
#8
Aditya D Joshi, Ekram Hossain, Cornelis J Elferink
The Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates a plethora of target genes. Historically, the AhR has been studied as a regulator of xenobiotic metabolizing enzyme genes, notably cytochrome P4501A1 encoded by CYP1A1, in response to the exogenous prototypical ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). AhR activity depends on binding to the xenobiotic response element (XRE) in partnership with the AhR nuclear translocator (Arnt). Recent studies identified stanniocalcin 2 (Stc2) as a novel AhR target gene responsive to the endogenous AhR agonist, cinnabarinic acid (CA)...
July 10, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28693112/association-of-prenatal-passive-smoking-and-metabolic-gene-polymorphisms-with-child-growth-from-birth-to-3years-of-age-in-the-hokkaido-birth-cohort-study-on-environment-and-children-s-health
#9
Titilola Serifat Braimoh, Sumitaka Kobayashi, Fumihiro Sata, Seiko Sasaki, Houman Goudarzi, Thamar Ayo Yila, Atsuko Araki, Chihiro Miyashita, Hisanori Minakami, Tsuyoshi Baba, Kazuo Sengoku, Reiko Kishi
Although the effects of prenatal passive smoking on birth weight have been reported, the effects of metabolic gene polymorphisms on passive smoking have not been studied. Therefore, we investigated the effects of maternal passive smoking and metabolic gene polymorphisms on child growth up to 3years of age using cotinine as a biomarker. We included 1356 Japanese participants in a prospective cohort between 2003 and 2007 (cotinine levels at the third trimester≤0.21ng/mL and 0.22 to 11.48ng/mL for non-passive and passive smokers, respectively), and measured child outcomes such as weight, length, head circumference, and Kaup index...
July 6, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28678150/metabolism-of-the-marine-phycotoxin-ptx-2-and-its-effects-on-hepatic-xenobiotic-metabolism-activation-of-nuclear-receptors-and-modulation-of-the-phase-i-cytochrome-p450
#10
Jimmy Alarcan, Estelle Dubreil, Antoine Huguet, Dominique Hurtaud-Pessel, Stefanie Hessel-Pras, Alfonso Lampen, Valérie Fessard, Ludovic Le Hegarat
PTX-2 is a marine biotoxin frequently found in shellfish that can lead to food intoxication in humans. Information regarding PTX-2 metabolism is scarce, and little is known of its effect on xenobiotic-metabolizing enzymes (XME) or its molecular pathways. The aim of this study was consequently to examine PTX-2 Phase I metabolism using rat and human liver S9 fractions, and also to assess the capability of PTX-2: (i) to modulate the gene expression of a panel of Phase I (CYP450) and II (UGT, SULT, NAT, and GST) enzymes, as well as the Phase III or 0 (ABC and SLCO) transporters in the human hepatic HepaRG cell line using qPCR; (ii) to induce specific CYP450 in HepaRG cells measured by immunolabeling detection and the measurement of the cells' activities; and (iii) to activate nuclear receptors and induce CYP promoter activities in HEK-T and HepG2 transfected cell lines using transactivation and reporter gene assay, respectively...
July 5, 2017: Toxins
https://www.readbyqxmd.com/read/28668703/dna-damage-and-repair-oxidative-stress-and-metabolism-biomarker-responses-in-lungs-of-rats-exposed-to-ambient-atmospheric-1-nitropyrene
#11
Ruijin Li, Lifang Zhao, Li Zhang, Minghui Chen, Chuan Dong, Zongwei Cai
1-Nitropyrene (1-NP) is a mutagenic and carcinogenic pollutant very widespread in the environment. However, the relative investigations on genotoxicity, oxidative stress and metabolic enzymes in lungs of mammalian caused by 1-NP have not been fully established. In this study, the 1-NP solutions at 3 dosages (1.0×10(-5), 4.0×10(-5) and 1.6×10(-4)mg/kg body weight) were respectively given to rats by the intratracheal instillation. The responses of 1-NP on DNA damage and repair, oxidative stress and metabolism biomarkers in rat lungs after exposure to 1-NP were measured...
June 20, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28664594/evaluation-of-baseline-frequency-of-sister-chromatid-exchanges-in-an-italian-population-according-to-age-sex-smoking-habits-and-gene-polymorphisms
#12
Alfredo Santovito, Claudio Gendusa, Piero Cervella
OBJECTIVES: Increased SCEs frequencies in human lymphocytes are an indicator of spontaneous chromosome instability and could be influenced by different exogenous and endogenous factors. In this study, we evaluated the influence of age, sex, smoking habits, and genetic polymorphisms on the background levels of SCEs in peripheral blood lymphocytes. METHODS: Two hundred-thirty healthy Italian subjects were recruited. Data about age, sex and smoking habits were recorded...
June 30, 2017: American Journal of Human Biology: the Official Journal of the Human Biology Council
https://www.readbyqxmd.com/read/28662488/transcriptional-response-in-rainbow-trout-oncorhynchus-mykiss-b-cells-and-thrombocytes-following-in-vivo-exposure-to-benzo-a-pyrene
#13
Laura J Phalen, Bernd Köllner, Natacha S Hogan, Michael R van den Heuvel
Immune toxicity of polycyclic aromatic hydrocarbons (PAHs) in fishes has been frequently reported but the reasons for differential cell toxicity remains unclear. Rainbow trout were exposed in vivo with a single intraperitoneal injection of corn oil or 100mg/kg of the immunotoxic PAH benzo[a]pyrene (B[a]P) in corn oil. Leukocytes were harvested from head kidney, spleen and blood after 14days, the optimal time for B cell depletion found in a previous study. The mRNA expression of five cytochrome P450 (CYP) enzymes, the aryl hydrocarbon receptor (AhR), and an intrinsic pathway apoptosis checkpoint (p53) in B cells and thrombocytes were examined...
July 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28662467/locus-specific-dna-methylation-changes-and-phenotypic-variability-in-children-with-attention-deficit-hyperactivity-disorder
#14
Sarojini M Sengupta, Alicia K Smith, Natalie Grizenko, Ridha Joober
Maternal smoking during pregnancy is the most commonly cited risk factor for ADHD. While the causal relation between this factor and ADHD is debated, several lines of evidence suggest that it modulates the severity of ADHD, particularly through higher association with conduct disorder (CD). We hypothesized that maternal smoking during pregnancy may be associated with differential methylation in selected genes in children with ADHD. DNA extracted from peripheral blood was used to examine methylation between 25 children exposed, and 22 children not exposed to maternal smoking during pregnancy...
June 20, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28656088/effects-of-berberine-on-the-secretion-of-cytokines-and-expression-of-genes-involved-in-cell-cycle-regulation-in-thp-1-monocytic-cell-line
#15
Saeed Mohammadi, Fakhri Sadat Seyedhoseini, Jahanbakhsh Asadi, Yaghoub Yazdani
OBJECTIVES: Current acute myeloid leukemia (AML) therapeutic strategies have irreversible side-effects. Berberine (BBR) is an isoquinoline alkaloid, which has been known as an aryl hydrocarbon receptor (AhR) ligand. AhR is a cytoplasmic receptor, which is involved in the regulation of cellular and immune responses. Here, we investigated the expression profile of genes involved in the cell cycle and different cytokines upon BBR-mediated AhR activation on AML THP-1 cell line. MATERIALS AND METHODS: THP-1 cells and normal monocytes were treated with different concentrations of BBR (10 μM, 25 μM, 50 μM, and 100 μM) for 24 and 48 hr...
May 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28655636/diesel-exhaust-particulate-associated-chemicals-attenuate-expression-of-cxcl10-in-human-primary-bronchial-epithelial-cells
#16
Kirsty Meldrum, Timothy W Gant, Martin O Leonard
Air pollution affects a large proportion of the population particularly in urban areas, with diesel particulates recognised as particular causes for concern in respiratory conditions such as asthma. In this study we examined the response of human primary airway epithelial cells to diesel particulate chemical extracts (DE) and characterised gene expression alterations using RNA-SEQ. Using the antagonist CH223191, DE induced CYP1A1 and attenuation of CXCL10 among other genes were observed to be aryl hydrocarbon receptor dependent...
June 24, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28652520/biochemical-characterization-of-variants-of-canine-cyp1a1-using-heterologous-3-expression
#17
Hee Jeong Yu, Seung Heon Lee, Seungwoo Lee, Yu Jung Choi, Dayoung Oh, Ki-Hoan Nam, YoungMin Yun, Doug-Young Ryu
Cytochrome P450 1A1 (CYP1A1) is a heme-containing mono-oxygenase involved in metabolism of environmental contaminants. Two variants of dog CYP1A1 with a single residue difference were identified and designated Sap1 and Sap2. Compared with Sap1, Sap2 had a Trp50Leu substitution. The biochemical characteristics of the variants were comparatively analyzed using heterologous expression in Escherichia coli. The membrane fraction of E. coli expressing Sap2 exhibited higher CYP holoprotein and heme contents than the Sap1-containing membranes, although the level of total CYP1A1 protein (i...
June 24, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/28652202/induction-of-cyp1a1-increases-gefitinib-induced-oxidative-stress-and-apoptosis-in-a549-cells
#18
Dan-Dan Wang, Yong Liu, Na Li, Yi Zhang, Qiang Jin, Da-Cheng Hao, Hai-Long Piao, Zi-Ru Dai, Guang-Bo Ge, Ling Yang
As the first selective EGFR tyrosine kinase inhibitor, gefitinib has been clinically demonstrated to be effective for certain cancer cell types with EGFR-active gene mutations. However, a number of gefitinib-associated adverse pulmonary events have been reported, which could lead to the discontinuation of gefitinib therapy. Although previous reports have implicated that CYP1A1-mediated bioactivation of gefitinib maybe a major reason for the pulmonary toxicity, the roles of CYP1A1 in gefitinib-associated toxicity and the related molecular mechanism have not been well-characterized...
June 23, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28648140/oxidation-of-1-chloropyrene-by-human-cyp1-family-and-cyp2a-subfamily-cytochrome-p450-enzymes-catalytic-roles-of-two-cyp1b1-and-five-cyp2a13-allelic-variants
#19
Tsutomu Shimada, Norie Murayama, Kensaku Kakimoto, Shigeo Takenaka, Young-Ran Lim, Sora Yeom, Donghak Kim, Hiroshi Yamazaki, F Peter Guengerich, Masayuki Komori
1. Chloropyrene, one of the major chlorinated polycyclic aromatic hydrocarbon contaminants, was incubated with human cytochrome P450 (P450 or CYP) enzymes including CYP1A1, 1A2, 1B1, 2A6, 2A13, 2B6, 2C9, 2D6, 2E1, 3A4, and 3A5. Catalytic differences in 1-chloropyrene oxidation by polymorphic two CYP1B1 and five CYP2A13 allelic variants were also examined. 2. CYP1A1 oxidized 1-chloropyrene at the 6- and 8-positions more actively than at the 3-position, while both CYP1B1.1 and 1B1.3 preferentially catalyzed 6-hydroxylation...
June 26, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28639016/accumulation-properties-of-polychlorinated-biphenyl-congeners-in-yusho-patients-and-prediction-of-their-cytochrome-p450-dependent-metabolism-by-in-silico-analysis
#20
Shusaku Hirakawa, Takashi Miyawaki, Tsuguhide Hori, Jumboku Kajiwara, Susumu Katsuki, Masashi Hirano, Yuka Yoshinouchi, Hisato Iwata, Chikage Mitoma, Masutaka Furue
In what has become known as the Yusho incident, thousands of people in western Japan were poisoned by the accidental ingestion of rice bran oil contaminated with polychlorinated biphenyls (PCBs) and various dioxins and dioxin-like compounds. In this study, we investigated the accumulation patterns of 69 PCB congeners in the blood of Yusho patients in comparison with those of non-exposed controls. The blood samples were collected at medical check-ups in 2004 and 2005. To compare the patterns of PCB congeners, we calculated the concentration ratio of each congener relative to the 2,2',4,4',5,5'-hexaCB (CB153) concentration...
June 21, 2017: Environmental Science and Pollution Research International
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