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COMT methylation

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https://www.readbyqxmd.com/read/28429453/tolcapone-induces-oxidative-stress-leading-to-apoptosis-and-inhibition-of-tumor-growth-in-neuroblastoma
#1
Tyler Maser, Maria Rich, David Hayes, Ping Zhao, Abhinav B Nagulapally, Jeffrey Bond, Giselle Saulnier Sholler
Catechol-O-methyltransferase (COMT) is an enzyme that inactivates dopamine and other catecholamines by O-methylation. Tolcapone, a drug commonly used in the treatment of Parkinson's disease, is a potent inhibitor of COMT and previous studies indicate that Tolcapone increases the bioavailability of dopamine in cells. In this study, we demonstrate that Tolcapone kills neuroblastoma (NB) cells in preclinical models by inhibition of COMT. Treating four established NB cells lines (SMS-KCNR, SH-SY5Y, BE(2)-C, CHLA-90) and two primary NB cell lines with Tolcapone for 48 h decreased cell viability in a dose-dependent manner, with IncuCyte imaging and Western blotting indicating that cell death was due to caspase-3-mediated apoptosis...
April 21, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28375049/delayed-o-methylation-of-l-dopa-in-mb-comt-deficient-mice-after-oral-administration-of-l-dopa-and-carbidopa
#2
Anne Tammimäki, Anu Aonurm-Helm, Pekka T Männistö
1. Catechol-O-methyltransferase (COMT) is involved in the O-methylation of L-DOPA, dopamine and other catechols. The enzyme is expressed in two isoforms: soluble (S-COMT), which resides in the cytoplasm, and membrane-bound (MB-COMT), which is anchored to intracellular membranes. 2. To obtain specific information on the functions of COMT isoforms, we studied how a complete MB-COMT deficiency affects the total COMT activity in the body, peripheral L-DOPA levels and metabolism after L-DOPA (10 mg kg(-1)) plus carbidopa (30 mg kg(-1)) administration by gastric tube in wild type and MB-COMT deficient mice...
April 4, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28361821/candidate-genes-for-alcohol-dependence-a-genetic-association-study-from-india
#3
Savita Malhotra, Debasish Basu, Madhu Khullar, Abhishek Ghosh, Neera Chugh
BACKGROUND & OBJECTIVES: Search for candidate genes for alcohol dependence (AD) has been inconsistent and inconclusive. Moreover, most of the research has been confined to a few specific ethnic groups. Hence, the aim of our study was to explore specific candidate genes for AD in north Indian male population. METHODS: In this clinic-based genetic association study, 210 males with AD and 200 controls matched for age, gender and ethnicity were recruited from the clinic and the general population, respectively...
November 2016: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/28321510/dna-methylation-patterns-of-behavior-related-gene-promoter-regions-dissect-the-gray-wolf-from-domestic-dog-breeds
#4
Zsofia Banlaki, Giulia Cimarelli, Zsofia Viranyi, Eniko Kubinyi, Maria Sasvari-Szekely, Zsolt Ronai
A growing body of evidence highlights the relationship between epigenetics, especially DNA methylation, and population divergence as well as speciation. However, little is known about how general the phenomenon of epigenetics-wise separation of different populations is, or whether population assignment is, possible based on solely epigenetic marks. In the present study, we compared DNA methylation profiles between four different canine populations: three domestic dog breeds and their ancestor the gray wolf...
March 21, 2017: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/28289795/-pharmacological-treatment-of-motor-symptoms-in-parkinson-s-diseases
#5
W H Jost
Since the 1960s many substance classes have been introduced for treatment of idiopathic Parkinson's disease. The most important and effective medication is levodopa (L-dopa) always in combination with a decarboxylase inhibitor. In addition, dopamine agonists, monoamine oxidase B (MAO-B) inhibitors, catechol-o-methyltransferase (COMT) inhibitors, N‑methyl-D-aspartate (NMDA) antagonists and very rarely anticholinergics are administered depending on the motor symptoms, age and a multitude of other factors. Fortunately, within the substance classes there are various preparations, which also have different effects...
March 13, 2017: Der Nervenarzt
https://www.readbyqxmd.com/read/28278373/potential-metabolic-activation-of-a-representative-c4-alkylated-polycyclic-aromatic-hydrocarbon-retene-1-methyl-7-isopropyl-phenanthrene-associated-with-the-deepwater-horizon-oil-spill-in-human-hepatoma-hepg2-cells
#6
Meng Huang, Clementina Mesaros, Linda C Hackfeld, Richard P Hodge, Tianzhu Zang, Ian A Blair, Trevor M Penning
Exposure to petrogenic polycyclic aromatic hydrocarbons (PPAHs) in the food chain is the major human health hazard associated with the Deepwater Horizon oil spill. C4-Phenanthrenes are representative PPAHs present in the crude oil and could contaminate the seafood. We describe the metabolism of a C4-phenanthrene regioisomer retene (1-methyl-7-isopropyl-phenanthrene) in human HepG2 cells as a model for metabolism in human hepatocytes. Retene because of its sites of alkylation cannot be metabolized to a diol-epoxide...
April 17, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28273198/effects-and-mechanisms-of-radiofrequency-ablation-of-renal-sympathetic-nerve-on-anti-hypertension-in-canine
#7
Wei Chen, Xiaohong Tang, Xiaofang Yang, Chunyan Weng, Kan Yang, Juan Wen, Hong Liu, Yang Wu
Background: Radiofrequency ablation of renal sympathetic nerve (RDN) shows effective BP reduction in hypertensive patients while the specific mechanisms remain unclear. Objective: We hypothesized that abnormal levels of norepinephrine (NE) and changes in NE-related enzymes and angiotensinconverting enzyme 2 (ACE2), angiotensin (Ang)-(1-7) and Mas receptor mediate the anti-hypertensive effects of RDN. Methods: Mean values of systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) were assessed at baseline and follow-up...
March 6, 2017: Arquivos Brasileiros de Cardiologia
https://www.readbyqxmd.com/read/28262266/ptsd-in-court-ii-risk-factors-endophenotypes-and-biological-underpinnings-in-ptsd
#8
REVIEW
Gerald Young
The second article in the series of three for the journal on "PTSD in Court" especially concerns the biological bases that have been found to be associated with PTSD (posttraumatic stress disorder). The cohering concepts in this section relate to risk factors; candidate genes; polygenetics; "gene×environment" interactions; epigenetics; endophenotypes; biomarkers; and connective networks both structurally and functionally (in terms of intrinsic connectivity networks, ICNs, including the DMN, SN, and CEN; that is, default mode, salience, and central executive networks, respectively)...
March 2, 2017: International Journal of Law and Psychiatry
https://www.readbyqxmd.com/read/28202018/de-novo-biosynthesis-of-pterostilbene-in-an-escherichia-coli-strain-using-a-new-resveratrol-o-methyltransferase-from-arabidopsis
#9
Kyung Taek Heo, Sun-Young Kang, Young-Soo Hong
BACKGROUND: Pterostilbene, a structural analog of resveratrol, has higher oral bioavailability and bioactivity than that of the parent compound; but is far less abundant in natural sources. Thus, to efficiently obtain this bioactive resveratrol analog, it is necessary to develop new bioproduction systems. RESULTS: We identified a resveratrol O-methyltransferase (ROMT) function from a multifunctional caffeic acid O-methyltransferase (COMT) originating from Arabidopsis, which catalyzes the transfer of a methyl group to resveratrol resulting in pterostilbene production...
February 15, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28195063/generation-of-membrane-bound-catechol-o-methyl-transferase-deficient-mice-with-disctinct-sex-dependent-behavioral-phenotype
#10
A Tammimaki, A Aonurm-Helm, F P Zhang, M Poutanen, G Duran-Torres, A Garcia-Horsman, P T Mannisto
Catechol-O-methyltransferase (COMT) has two isoforms: soluble (S-COMT), which resides in the cytoplasm, and membrane-bound (MB-MT), anchored to intracellular membranes. COMT is involved in the O-methylation of L-DOPA, dopamine and other catechols. The exact role of MB-COMT is still mostly unclear. We wanted to create a novel genetically modified mouse model that specifically lacks MB-COMT activity and to study their behavioral phenotype. MB-COMT knock-in mutant mice were generated by introducing two point mutations in exon 2 of the Comt gene (ATGCTG->GAGCTC disabling the function of the P2 promoter and allowing only the P1-regulated S-COMT transcription...
December 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28192769/disorganization-at-the-stage-of-schizophrenia-clinical-outcome-clinical-biological-study
#11
A Nestsiarovich, V Obyedkov, H Kandratsenka, M Siniauskaya, I Goloenko, N Waszkiewicz
BACKGROUND: According to the multidimensional model of schizophrenia, three basic psychopathological dimensions constitute its clinical structure: positive symptoms, negative symptoms and disorganization. The latter one is the newest and the least studied. Our aim was to discriminate disorganization in schizophrenia clinical picture and to identify its distinctive biological and socio-psychological particularities and associated genetic and environmental factors. METHODS: We used SAPS/SANS psychometrical scales, scales for the assessment of patient's compliance, insight, social functioning, life quality...
May 2017: European Psychiatry: the Journal of the Association of European Psychiatrists
https://www.readbyqxmd.com/read/28154783/leptin-influences-estrogen-metabolism-and-increases-dna-adduct-formation-in-breast-cancer-cells
#12
Samia Shouman, Mohamed Wagih, Marwa Kamel
OBJECTIVE: The elevated incidence of obesity has been paralleled with higher risks of breast cancer. High adiposity increases leptin secretion from adipose tissue, which in turn increases cancer cell proliferation. The interplay between leptin and estrogen is one of the mechanisms through which leptin influences breast carcinogenesis. An unbalanced estrogen metabolism increases the formations of catechol estrogen quinones, DNA adducts, and cancer mutations. This study aims to investigate the effect of leptin on some estrogen metabolic enzymes and DNA adduction in breast cancer cells...
December 2016: Cancer Biology & Medicine
https://www.readbyqxmd.com/read/28102561/stressful-life-events-and-catechol-o-methyl-transferase-comt-gene-in-bipolar-disorder
#13
Georgina M Hosang, Helen L Fisher, Sarah Cohen-Woods, Peter McGuffin, Anne E Farmer
BACKGROUND: A small body of research suggests that gene-environment interactions play an important role in the development of bipolar disorder. The aim of the present study is to contribute to this work by exploring the relationship between stressful life events and the catechol-O-methyl-transferase (COMT) Val(158) Met polymorphism in bipolar disorder. METHODS: Four hundred eighty-two bipolar cases and 205 psychiatrically healthy controls completed the List of Threatening Experiences Questionnaire...
January 19, 2017: Depression and Anxiety
https://www.readbyqxmd.com/read/28074437/aberrant-endometrial-dna-methylome-of-homeobox-a10-and-catechol-o-methyltransferase-in-endometriosis
#14
Fei Ji, Xinhua Yang, Yan He, Hui Wang, Aixingzi Aili, Yan Ding
PURPOSE: Differential methylation of both HOXA10 and catechol-O-methyltransferase (COMT) has been reported in different endometrium disorders, and the two genes are linked through the estrogen pathway. The current study investigates the DNA methylation of HOXA10 and COMT in ectopic and eutopic endometrial tissues and its correlation with and the occurrence of endometriosis in women from Xinjiang province in China. METHODS: In the current study, 120 patients with endometriosis were recruited from our hospital between January 2011 and June 2014...
March 2017: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/28071803/effects-of-catechol-o-methyl-transferase-inhibition-on-anti-inflammatory-activity-of-luteolin-metabolites
#15
Sang Keun Ha, Jin-Ah Lee, Eun Jung Cho, Inwook Choi
Although luteolin is known to have potent anti-inflammatory activities, much less information has been provided on such activities of its hepatic metabolites. Luteolin was subjected to hepatic metabolism in HepG2 cells either without or with catechol O-methyl transferase (COMT) inhibitor. To identify hepatic metabolites of luteolin without (luteolin metabolites, LMs) or with COMT inhibitor (LMs+CI), metabolites were treated by β-glucuronidase and sulfatase, and found that they were composed of glucuronide and sulfate conjugates of diosmetin in LMs or these conjugates of luteolin in LMs+CI...
January 10, 2017: Journal of Food Science
https://www.readbyqxmd.com/read/28031430/metabolic-disposition-of-luteolin-is-mediated-by-the-interplay-of-udp-glucuronosyltransferases-and-catechol-o-methyltransferases-in-rats
#16
Liping Wang, Qingwei Chen, Lijun Zhu, Qiang Li, Xuejun Zeng, Linlin Lu, Ming Hu, Xinchun Wang, Zhongqiu Liu
Luteolin partially exerts its biologic effects via its metabolites catalyzed by UDP-glucuronosyltransferases (UGTs) and catechol-O-methyltransferases (COMTs). However, the interplay of UGTs and COMTs in mediating luteolin disposition has not been well clarified. In this study, we investigated the glucuronidation and methylation pathways of luteolin mediated by the interplay of UGTs and COMTs in vivo and in vitro. A total of nine luteolin metabolites was detected in rat plasma and bile by liquid chromatography-tandem mass spectrometry, namely, three glucuronides, two methylated metabolites, and four methylated glucuronides...
March 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/27939670/identification-and-characterization-of-a-catechol-o-methyltransferase-cdna-in-the-catfish-heteropneustes-fossilis-tissue-sex-and-seasonal-variations-and-effects-of-gonadotropin-and-2-hydroxyestradiol-17%C3%AE-on-mrna-expression
#17
R Chaube, A Rawat, R M Inbaraj, J Bobe, Y Guiguen, A Fostier, K P Joy
Catechol-O-methyltransferase (COMT) is involved in the methylation and inactivation of endogenous and xenobiotic catechol compounds, and serves as a common biochemical link in the catecholamine and catecholestrogen metabolism. Studies on cloning, sequencing and function characterization comt gene in lower vertebrates like fish are fewer. In the present study, a full-length comt cDNA of 1442bp with an open-reading frame (ORF) of 792bp, and start codon (ATG) at nucleotide 162 and stop codon (TAG) at nucleotide 953 was isolated and characterized in the stinging catfish Heteropneustes fossilis (accession No...
December 8, 2016: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/27930497/the-comt-val158met-polymorphism-is-associated-with-response-to-add-on-dextromethorphan-treatment-in-bipolar-disorder
#18
Sheng-Yu Lee, Shiou-Lan Chen, Tzu-Yun Wang, Yun-Hsuan Chang, Po See Chen, San-Yuan Huang, Nian-Sheng Tzeng, Liang-Jen Wang, I Hui Lee, Kao Ching Chen, Yen Kuang Yang, Ru-Band Lu
PURPOSE/BACKGROUND: We previously conducted a randomized, double-blind, controlled, 12-week study evaluating the effect of add-on dextromethorphan (DM), a noncompetitive N-methyl-D-aspartate receptor antagonist, on patients with bipolar disorder (BD) treated using valproate (VPA), which showed negative clinical differences. The genetic variation between each individual may be responsible for interindividual differences. The catechol-O-methyltransferase (COMT) gene has been a candidate gene for BD...
February 2017: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/27914298/effects-of-environmental-noise-exposure-on-dna-methylation-in-the-brain-and-metabolic-health
#19
Liqiong Guo, Peng-Hui Li, Hua Li, Elena Colicino, Silvia Colicino, Yi Wen, Ruiping Zhang, Xiaotian Feng, Timothy M Barrow, Akin Cayir, Andrea A Baccarelli, Hyang-Min Byun
Environmental noise exposure is associated with adverse effects on human health including hearing loss, heart disease, and changes in stress-related hormone levels. Alteration in DNA methylation in response to environmental exposures is a well-known phenomenon and it is implicated in many human diseases. Understanding how environmental noise exposures affect DNA methylation patterns may help to elucidate the link between noise and adverse effects on health. In this pilot study we examined the effects of environmental noise exposure on DNA methylation of genes related to brain function and investigated whether these changes are related with metabolic health...
November 30, 2016: Environmental Research
https://www.readbyqxmd.com/read/27904710/the-comt-rs165599-gene-polymorphism-contributes-to-chemotherapy-induced-cognitive-impairment-in-breast-cancer-patients
#20
Huaidong Cheng, Wen Li, Chen Gan, Bo Zhang, Qianqian Jia, Kai Wang
The present study aimed to investigate the effect of genetic polymorphisms of catechol-O-methyl transferase (COMT), apolipoprotein E (APOE), and brain derived neurotrophic factor (BDNF) on the modulation of the chemotherapy-induced cognitive impairment (CICI) in breast cancer patients. Eighty triple negative breast cancer (TNBC) and 165 non-triple negative breast cancer (NTNBC) patients were selected, and subjected to a number of neuropsychological tests, including memory questionnaires, before and after chemotherapy...
2016: American Journal of Translational Research
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