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COMT methylation

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https://www.readbyqxmd.com/read/28102561/stressful-life-events-and-catechol-o-methyl-transferase-comt-gene-in-bipolar-disorder
#1
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
#2
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...
January 10, 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
#3
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
#4
Liping Wang, Qingwei Chen, Lijun Zhu, Qiang Li, Xuejun Zeng, Linlin Lu, Ming Hu, Xinchun Wang, Zhongqiu Liu
Luteolin partialy exerts its biological 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 were detected in rat plasma and bile by liquid chromatography - tandem mass spectrometry, namely, three glucuronides, two methylated metabolites, and four methylated glucuronides...
December 28, 2016: 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
#5
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
#6
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
#7
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
#8
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
https://www.readbyqxmd.com/read/27890888/cloning-and-expression-of-a-novel-catechol-o-methyltransferase-in-common-marmosets
#9
Shotaro Uehara, Yasuhiro Uno, Takashi Inoue, Erika Sasaki, Hiroshi Yamazaki
Catechol-O-methyltransferase (COMT) catalyzes the O-methylation of endogenous catechol amines and estrogens and exogenous catechol-type of drugs. A Parkinson's disease model of common marmoset (Callithrix jacchus) has been widely used in preclinical studies to evaluate inhibitory potential of new drug candidates on marmoset COMT. Despite COMT inhibitors could potentiate the pharmacological action of levodopa on Parkinson's disease in animal models, marmoset COMT cDNA has not yet been identified and characterized...
November 26, 2016: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/27886638/preliminary-evidence-that-negative-symptom-severity-relates-to-multilocus-genetic-profile-for-dopamine-signaling-capacity-and-d2-receptor-binding-in-healthy-controls-and-in-schizophrenia
#10
Sarah A Eisenstein, Ryan Bogdan, Ling Chen, Stephen M Moerlein, Kevin J Black, Joel S Perlmutter, Tamara Hershey, Deanna M Barch
Deficits in central, subcortical dopamine (DA) signaling may underlie negative symptom severity, particularly anhedonia, in healthy individuals and in schizophrenia. To investigate these relationships, we assessed negative symptoms with the Schedule for the Assessment of Negative Symptoms and the Brief Negative Symptom Scale (BNSS) and self-reported anhedonia with the Scales for Physical and Social Anhedonia (SPSA), Temporal Experience of Pleasure Scale, and Snaith-Hamilton Pleasure Scale in 36 healthy controls (HC), 27 siblings (SIB) of individuals with schizophrenia, and 66 individuals with schizophrenia or schizoaffective disorder (SCZ)...
November 17, 2016: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/27883923/gilles-de-la-tourette-syndrome-is-associated-with-hypermethylation-of-the-dopamine-d2-receptor-gene
#11
Kirsten R Müller-Vahl, Gesa Loeber, Alexandra Kotsiari, Linda Müller-Engling, Helge Frieling
Several lines of evidence support a "dopaminergic hypothesis" in the pathophysiology of Gilles de la Tourette syndrome (TS). The aim of this study was to investigate for the first time epigenetic changes in DNA methylation in different dopamine genes in adult patients with TS. We included 51 well characterized adult patients with TS (41 males, 10 females, mean age = 35 ± 12.6 years, range, 18-71 years) and compared results with data from a group of 51 sex- and age-matched healthy controls. Bisulfite sequencing was used to measure peripheral DNA methylation of the dopamine transporter (DAT), the dopamine D2 receptor (DRD2), and the catechol-O-methyltransferase (COMT) genes...
November 12, 2016: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/27882177/catechol-o-methyltransferase-promoter-hypomethylation-is-associated-with-the-risk-of-coronary-heart-disease
#12
Jinyan Zhong, Xiaoying Chen, Nan Wu, Caijie Shen, Hanbin Cui, Weiping Du, Zhaoxia Zhang, Mingjun Feng, Junsong Liu, Shaoyi Lin, Lulu Zhang, Jian Wang, Xiaomin Chen, Shiwei Duan
Catechol-O-methyltransferase (COMT) gene variation is known to be associated with the risk of acute coronary events. The purpose of the present study was to investigate the contribution of COMT promoter methylation towards the risk of coronary heart disease (CHD). COMT methylation was evaluated in 48 CHD cases and 48 well-matched non-CHD controls using bisulfite pyrosequencing technology. The results demonstrated that CHD cases had a significantly lower level of methylation at COMT CpG3 sites compared with the controls (33...
November 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27826992/the-val158met-polymorphism-in-comt-gene-and-cancer-risk-role-of-endogenous-and-exogenous-catechols
#13
Katrin Sak
Catechol-O-methyltransferase, COMT, is an important phase II enzyme catalyzing the transfer of a methyl-group from S-adenosylmethionine to a catechol-containing substrate molecule. A genetic variant Val158Met in the COMT gene leads to a several-fold decrease in the enzymatic activity giving rise to the accumulation of potentially carcinogenic endogenous catechol estrogens and their reactive intermediates and increasing thus the risk of tumorigenesis. However, numerous association studies between the COMT genotype and susceptibility to various malignancies have shown inconsistent and controversial findings indicating that additional gene-gene and gene-environment interactions might be crucial in modulating the physiological role of the COMT...
November 9, 2016: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/27808339/differentiated-caco-2-cell-monolayers-exhibit-adaptation-in-the-transport-and-metabolism-of-flavan-3-ols-with-chronic-exposure-to-both-isolated-flavan-3-ols-and-enriched-extracts
#14
Benjamin W Redan, Mohammad Chegeni, Mario G Ferruzzi
The relatively low oral bioavailability of flavan-3-ols from acute doses is commonly highlighted as a limitation when considering the biological significance of these compounds. However, evidence suggests that the absorption of flavan-3-ols may be enhanced during periods of repeated exposure which is more representative of dietary patterns. To explore changes occurring in the upper small intestine from repeated exposure to dietary flavan-3-ols, Caco-2 human intestinal cells were cultured and differentiated in the presence of isolated flavan-3-ols epigallocatechin gallate (EGCG) and epicatechin (EC) or flavan-3-ol-rich green tea and grape seed extracts...
November 3, 2016: Food & Function
https://www.readbyqxmd.com/read/27761079/elucidation-of-molecular-mechanism-s-of-cognition-enhancing-activity-of-bacomind-%C3%A2-a-standardized-extract-of-bacopa-monnieri
#15
Shekhar Dethe, M Deepak, Amit Agarwal
BACKGROUND: Bacopa monnieri (L.) Wettst., commonly known as Brahmi, is renowned in Indian traditional system for its potent memory enhancing activity, which has been validated by various scientific studies. OBJECTIVE: The objective of this study was to understand the molecular mechanism of memory enhancing activity of BacoMind(®) (BM), a standardized extract of B. monnieri. MATERIALS AND METHODS: BM was screened in vitro in a panel of cell-free and receptor-transfected cell assays...
July 2016: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/27753212/methamphetamine-induced-psychosis-is-associated-with-dna-hypomethylation-and-increased-expression-of-akt1-and-key-dopaminergic-genes
#16
Shabnam Nohesara, Mohammad Ghadirivasfi, Mahmood Barati, Mohammad-Reza Ghasemzadeh, Samira Narimani, Zohreh Mousavi-Behbahani, Mohammadtaghi Joghataei, Mansoureh Soleimani, Mozhgan Taban, Soraya Mehrabi, Sam Thiagalingam, Hamid Mostafavi Abdolmaleky
Methamphetamine, one of the most frequently used illicit drugs worldwide, can induce psychosis in a large fraction of abusers and it is becoming a major problem for the health care institutions. There is some evidence that genetic and epigenetic factors may play roles in methamphetamine psychosis. In this study, we examined methamphetamine-induced epigenetic and expression changes of several key genes involved in psychosis. RNA and DNA extracted from the saliva samples of patients with methamphetamine dependency with and without psychosis as well as control subjects (each group 25) were analyzed for expression and promoter DNA methylation status of DRD1, DRD2, DRD3, DRD4, MB-COMT, GAD1, and AKT1 using qRT-PCR and q-MSP, respectively...
December 2016: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/27704827/how-large-should-the-qm-region-be-in-qm-mm-calculations-the-case-of-catechol-o-methyltransferase
#17
Heather J Kulik, Jianyu Zhang, Judith P Klinman, Todd J Martínez
Hybrid quantum mechanical-molecular mechanical (QM/MM) simulations are widely used in studies of enzymatic catalysis. Until recently, it has been cost prohibitive to determine the asymptotic limit of key energetic and structural properties with respect to increasingly large QM regions. Leveraging recent advances in electronic structure efficiency and accuracy, we investigate catalytic properties in catechol O-methyltransferase, a prototypical methyltransferase critical to human health. Using QM regions ranging in size from reactants-only (64 atoms) to nearly one-third of the entire protein (940 atoms), we show that properties such as the activation energy approach within chemical accuracy of the large-QM asymptotic limits rather slowly, requiring approximately 500-600 atoms if the QM residues are chosen simply by distance from the substrate...
November 10, 2016: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/27685665/design-of-potent-and-druglike-nonphenolic-inhibitors-for-catechol-o-methyltransferase-derived-from-a-fragment-screening-approach-targeting-the-s-adenosyl-l-methionine-pocket
#18
Christian Lerner, Roland Jakob-Roetne, Bernd Buettelmann, Andreas Ehler, Markus Rudolph, Rosa María Rodríguez Sarmiento
A fragment screening approach designed to target specifically the S-adenosyl-l-methionine pocket of catechol O-methyl transferase allowed the identification of structurally related fragments of high ligand efficiency and with activity on the described orthogonal assays. By use of a reliable enzymatic assay together with X-ray crystallography as guidance, a series of fragment modifications revealed an SAR and, after several expansions, potent lead compounds could be obtained. For the first time nonphenolic and small low nanomolar potent, SAM competitive COMT inhibitors are reported...
November 23, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27619075/iq-and-hemizygosity-for-the-val-158-met-functional-polymorphism-of-comt-in-22q11ds
#19
Colleen P Franconi, Donna McDonald-McGinn, Elaine H Zackai, Meghan A McNamara, Harold Salmons, Edward Moss, Raquel E Gur, Marcella Devoto, Beverly S Emanuel
22q11.2 Deletion Syndrome (22q11DS) is a multisystem disorder caused by a hemizygous deletion within 22q11.2. Patients with the deletion display a wide range of cognitive deficits. The gene catechol-O-methyl-transferase (COMT) resides in the typically deleted region of 22q11.2 and is rendered hemizygous in individuals affected by the 22q11DS. COMT is a critical enzyme in the degradation of catecholamine neurotransmitters in the brain. A functional polymorphism, Val(158) Met, has been associated with a variety of neurocognitive outcomes...
December 2016: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/27564542/computational-investigation-of-the-interplay-of-substrate-positioning-and-reactivity-in-catechol-o-methyltransferase
#20
Niladri Patra, Efthymios I Ioannidis, Heather J Kulik
Catechol O-methyltransferase (COMT) is a SAM- and Mg2+-dependent methyltransferase that regulates neurotransmitters through methylation. Simulations and experiments have identified divergent catecholamine substrate orientations in the COMT active site: molecular dynamics simulations have favored a monodentate coordination of catecholate substrates to the active site Mg2+, and crystal structures instead preserve bidentate coordination along with short (2.65 Å) methyl donor-acceptor distances. We carry out longer dynamics (up to 350 ns) to quantify interconversion between bidentate and monodentate binding poses...
2016: PloS One
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