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CYP1A1

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https://www.readbyqxmd.com/read/28812970/indole-3-carbinol-induces-g1-cell-cycle-arrest-and-apoptosis-through-aryl-hydrocarbon-receptor-in-thp-1-monocytic-cell-line
#1
Saeed Mohammadi, Fakhri Sadat Seyedhosseini, Nasser Behnampour, Yaghoub Yazdani
OBJECTIVES: The role of aryl hydrocarbon receptor (AhR) in carcinogenesis has been studied recently. Indole-3-carbinol (I3C) is an AhR agonist and a potential anticancer agent. Here, we investigated the effects of I3C on cell cycle progression and apoptosis through activation of AhR on THP-1 acute myeloid leukemia (AML) cell line. METHODS: MTT viability assay was used to measure the cytotoxic effects of I3C on THP-1 cells. Apoptosis and cell cycle assays were investigated using flow cytometry...
October 2017: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/28806569/metabolic-profiling-of-dehydrodiisoeugenol-using-xenobiotic-metabolomics
#2
Qian-Qian Lv, Xiao-Nan Yang, Dong-Mei Yan, Wei-Qing Liang, Hong-Ning Liu, Xiu-Wei Yang, Fei Li
Dehydrodiisoeugenol (DDIE), a representative and major benzofuran-type neolignan in Myristica fragrans Houtt., shows anti-inflammatory and anti-bacterial actions. In order to better understand its pharmacological properties, xenobiotic metabolomics was used to determine the metabolic map of DDIE and its influence on endogenous metabolites. Total thirteen metabolites of DDIE were identified through in vivo and in vitro metabolism, and seven of them were reported for the first time in the present study. The identity of DDIE metabolites was achieved by comparison of the MS/MS fragmentation pattern with DDIE using ultra-performance chromatography electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI- QTOFMS)...
July 31, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28803404/polymorphisms-in-xrcc1-ercc2-and-ercc3-dna-repair-genes-cyp1a1-xenobiotic-metabolism-gene-and-tobacco-are-associated-with-bladder-cancer-susceptibility-in-tunisian-population
#3
Molka Feki-Tounsi, Rim Khlifi, Ibtihel Louati, Mohamed Fourati, Mohamed-Nabil Mhiri, Amel Hamza-Chaffai, Ahmed Rebai
Other than the established environmental risk factors associated with bladder cancer (BC), little is known about the genetic variations determining the individual susceptibility of this complex disease. This study aimed to investigate the relationship of BC with environmental agents and polymorphisms in XRCC1, ERCC2, and ERCC3 DNA repair genes and CYP1A1, CYP2D6, NAT1, and NAT2 xenobiotic metabolism genes through a hospital-based case-control study in Tunisia. The selection of the single nucleotide polymorphisms (SNPs) (rs25487, rs 13181, rs415407, rs446421, rs1058172, rs4921880, and rs1208) was performed using the dbSNP database...
August 12, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28800488/benzo-a-pyrene-induced-a-mitochondria-independent-apoptosis-of-liver-in-juvenile-chinese-rare-minnows-gobiocypris-rarus
#4
Jinmiao Zha, Xiangsheng Hong, Haiou Rao, Lilai Yuan, Zijian Wang, Satyanarayanan Senthil Kumaran
To examine the effects of BaP on tissue apoptosis, laboratory studies were conducted using juvenile Chinese rare minnows (Gobiocypris rarus) exposed to 1, 5, 20, and 80 μg/L of BaP for 28 days. The post-treatment pathological findings in the liver were associated with hepatocyte swelling, karyopyknosis, and karyorrhexis. Moreover, an increase in the goblet cells in the intestine, epithelial hyperplasia of the gills and fusion of gill lamellae were observed. Significant increases in hepatocyte apoptosis using the TUNEL stain were observed in the liver tissue but not in the intestine and gills...
August 8, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28790146/cyp1a1-mediated-intramolecular-rearrangement-of-aminoazepane-in-gdc-0339
#5
Ryan H Takahashi, Xiaojing Wang, Nathaniel L Segraves, Jing Wang, Jae H Chang, Siamak Cyrus Khojasteh, Shuguang Ma
GDC-0339 is a novel small molecule pan-Pim kinase inhibitor that was discovered as a potential treatment for multiple myeloma. During the in vitro and in vivo metabolite profiling of GDC-0339, a metabolite was detected that had the same elemental composition as the parent but was distinct based on chromatographic separation and mass spectrometric fragmentation pattern. High resolution MS/MS data indicated the metabolite was modified at the aminoazepane moiety. The structure was solved by NMR analysis of the isolated metabolite and further confirmed by comparing it to a synthetic standard...
August 8, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28782952/biotransformation-of-chrysin-to-baicalein-selective-c6-hydroxylation-of-5-7-dihydroxyflavone-using-whole-yeast-cells-stably-expressing-human-cyp1a1-enzyme
#6
Ibidapo S Williams, Shifali Chib, Vijay K Nuthakki, Linda Gatchie, Prashant Joshi, Niteen A Narkhede, Ram A Vishwakarma, Sandip B Bharate, Saurabh Saran, Bhabatosh Chaudhuri
Naturally occurring polyphenolic compounds are of medicinal importance because of their unique antioxidant, anticancer, and chemopreventive properties. Baicalein, a naturally occurring polyhydroxy flavonoid possessing a diverse range of pharmacological activities, has been used in traditional medicines for treatment of various ailments. Apart from its isolation from natural sources, its synthesis has been reported via multistep chemical approaches. Here, we report a preparative-scale biotransformation, using whole yeast cells stably expressing human cytochrome P450 1A1 (CYP1A1) enzyme that allows regioselective C6-hydroxylation of 5,7-dihydroxyflavone (chrysin) to form 5,6,7-trihydroxyflavone (baicalein)...
August 15, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28780123/molecular-insights-into-the-role-of-a-distal-f240a-mutation-that-alters-cyp1a1-activity-towards-persistent-organic-pollutants
#7
Veronika Navrátilová, Markéta Paloncýová, Karel Berka, Shintaro Mise, Yuki Haga, Chisato Matsumura, Toshiyuki Sakaki, Hideyuki Inui, Michal Otyepka
BACKGROUND: Cytochromes P450 are major drug-metabolizing enzymes involved in the biotransformation of diverse xenobiotics and endogenous chemicals. Persistent organic pollutants (POPs) are toxic hydrophobic compounds that cause serious environmental problems because of their poor degradability. This calls for rational design of enzymes capable of catalyzing their biotransformation. Cytochrome P450 1A1 isoforms catalyze the biotransformation of some POPs, and constitute good starting points for the design of biocatalysts with tailored substrate specificity...
August 2, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28764905/comparison-of-short-and-long-term-exposure-effects-of-cruciferous-and-apiaceous-vegetables-on-carcinogen-metabolizing-enzymes-in-wistar-rats
#8
Jae Kyeom Kim, Noemia Strapazzon, Cynthia M Gallaher, Dwight R Stoll, William Thomas, Daniel D Gallaher, Sabrina P Trudo
Cruciferous and apiaceous vegetables may be chemopreventive due to their ability to modulate carcinogen-metabolizing enzymes but whether the effects on such enzymes are sustained over time is unknown. To examine the short- and long-term effects of the vegetables, rats were fed one of four diets for 7, 30, or 60 d: AIN-93G, CRU (21% cruciferous vegetables-fresh broccoli, green cabbage, watercress), API (9% apiaceous vegetables - fresh parsnips, celery), or API + CRU (10.5% CRU + 4.5% API). Although CRU increased activity and protein expression of cytochrome P450 (CYP) 1A1 and CYP1A2 after 7 d, only activity was sustained after 30 and 60 d...
July 29, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28764121/ahr-and-cyp1a-expression-link-historical-contamination-events-to-modern-day-developmental-effects-in-the-american-alligator
#9
Matthew D Hale, Thomas M Galligan, Thomas R Rainwater, Brandon C Moore, Philip M Wilkinson, Louis J Guillette, Benjamin B Parrott
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that initiates a transcriptional pathway responsible for the expression of CYP1A subfamily members, key to the metabolism of xenobiotic compounds. Toxic planar halogenated aromatic hydrocarbons, including dioxin and PCBs, are capable of activating the AHR, and while dioxin and PCB inputs into the environment have been dramatically curbed following strict regulatory efforts in the United States, they persist in the environment and exposures remain relevant today...
July 27, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28756226/specific-packaging-and-circulation-of-cytochromes-p450-especially-2e1-isozyme-in-human-plasma-exosomes-and-their-implications-in-cellular-communications
#10
Santosh Kumar, Namita Sinha, Kelli A Gerth, Mohammad A Rahman, Murali M Yallapu, Narasimha M Midde
Cytochrome P450 (CYP) enzymes metabolize the majority of xenobiotics and are mainly found in hepatic and some extra-hepatic cells. However, their presence and functional role in exosomes, small extracellular vesicles that are secreted from various cells into extracellular fluids including plasma, is unknown. In this study, we analyzed the expression and biological activity of CYP enzymes in human plasma exosomes. First, we optimized isolation of plasma exosomes and characterized them for their physical properties and quality...
July 26, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28732322/effects-of-environmental-pollutants-on-signaling-pathways-in-rat-pituitary-gh3-adenoma-cells
#11
Nicoletta Fortunati, Federica Guaraldi, Valentina Zunino, Federica Penner, Valentina D'Angelo, Francesco Zenga, Francesca Pecori Giraldi, Maria Graziella Catalano, Emanuela Arvat
An increased rate of acromegaly was reported in industrialized areas, suggesting an involvement of environmental pollutants in the pathogenesis and behavior of GH-secreting pituitary adenomas. Based on these premises, the aim of the study was to evaluate the effects of some widely diffused pollutants (i.e. benzene, BZ; bis(2-ethylhexyl) phthalate, DEHP and polychlorinated biphenyls, PCB) on growth hormone secretion, the somatostatin and estrogenic pathways, viability and proliferation of rat GH-producing pituitary adenoma (GH3) cells...
July 18, 2017: Environmental Research
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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-metastasis-associated-protein-2-selectively-induces-stanniocalcin-2-expression
#19
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 its 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)...
September 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
#20
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
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