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https://www.readbyqxmd.com/read/27739310/-glycine-n-methyltransferase-and-malignant-diseases-of-the-prostate
#1
Z Heger, T Eckschlager, M Stiborová, V Adam
BACKGROUND: Prostate cancer (PC) constitutes a heterogeneous group of diseases with high prevalence rates that are still increasing, particularly in western countries. Since 1980, prostate specific antigen (PSA) and other diagnostic approaches have been used for PC screening; however, some of these approaches are often deemed painful and cause invasive damage of tissue. Therefore, molecular approaches to PC diagnosis are attracting increasing attention, potentially providing patients with less stressful situations and providing better diagnoses and even prognostic information...
2016: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/27716281/glycine-n-methyltransferase-deficiency-in-female-mice-impairs-insulin-signaling-and-promotes-gluconeogenesis-by-modulating-the-pi3k-akt-pathway-in-the-liver
#2
Yi-Jen Liao, Tzong-Shyuan Lee, Yuh-Ching Twu, Shih-Ming Hsu, Ching-Ping Yang, Chung-Kwe Wang, Yu-Chih Liang, Yi-Ming Arthur Chen
BACKGROUND: Glycine N-methyltransferase (GNMT) is abundantly expressed in the normal liver but is down-regulated in liver cancer tissues. GNMT knockout (Gnmt-/-) mice can spontaneously develop chronic hepatitis, fatty liver, and liver cancer. We previously demonstrated that hepatic GNMT is decreased in high-fat-diet-induced type 2 diabetes mellitus, but its contribution to metabolic syndrome is unclear. Here we show that GNMT modulates key aspects of metabolic syndrome in mice. METHODS: Eleven-week-old Gnmt-/- and wild-type (WT) mice with a C57BL/6 genetic background were used in this study...
October 4, 2016: Journal of Biomedical Science
https://www.readbyqxmd.com/read/27648945/downregulation-of-mir-150-expression-by-dna-hypermethylation-is-associated-with-high-2-hydroxy-4-methylthio-butanoic-acid-induced-hepatic-cholesterol-accumulation-in-nursery-piglets
#3
Yimin Jia, Mingfa Ling, Luchu Zhang, Shuxia Jiang, Yusheng Sha, Ruqian Zhao
Excess 2-hydroxy-(4-methylthio)butanoic acid (HMB) supplementation induces hyperhomocysteinemia, which contributes to hepatic cholesterol accumulation. However, it is unclear whether and how high levels of HMB break hepatic cholesterol homeostasis in nursery piglets. In this study, HMB oversupplementation suppressed food intake and decreased body weight in nursery piglets. Hyperhomocysteinemia and higher hepatic cholesterol accumulation were observed in HMB groups. Accordingly, HMB significantly increased the protein content of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) and glycine N-methyltransferase (GNMT) but decreased that of acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT1)...
October 12, 2016: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/27526323/modulation-of-long-noncoding-rnas-by-risk-snps-underlying-genetic-predispositions-to-prostate-cancer
#4
Haiyang Guo, Musaddeque Ahmed, Fan Zhang, Cindy Q Yao, SiDe Li, Yi Liang, Junjie Hua, Fraser Soares, Yifei Sun, Jens Langstein, Yuchen Li, Christine Poon, Swneke D Bailey, Kinjal Desai, Teng Fei, Qiyuan Li, Dorota H Sendorek, Michael Fraser, John R Prensner, Trevor J Pugh, Mark Pomerantz, Robert G Bristow, Mathieu Lupien, Felix Y Feng, Paul C Boutros, Matthew L Freedman, Martin J Walsh, Housheng Hansen He
Long noncoding RNAs (lncRNAs) represent an attractive class of candidates to mediate cancer risk. Through integrative analysis of the lncRNA transcriptome with genomic data and SNP data from prostate cancer genome-wide association studies (GWAS), we identified 45 candidate lncRNAs associated with risk to prostate cancer. We further evaluated the mechanism underlying the top hit, PCAT1, and found that a risk-associated variant at rs7463708 increases binding of ONECUT2, a novel androgen receptor (AR)-interacting transcription factor, at a distal enhancer that loops to the PCAT1 promoter, resulting in upregulation of PCAT1 upon prolonged androgen treatment...
October 2016: Nature Genetics
https://www.readbyqxmd.com/read/27355841/convergent-mechanistic-features-between-the-structurally-diverse-n-and-o-methyltransferases-glycine-n-methyltransferase-and-catechol-o-methyltransferase
#5
Jianyu Zhang, Judith P Klinman
Although an enormous and still growing number of biologically diverse methyltransferases have been reported and identified, a comprehensive understanding of the enzymatic methyl transfer mechanism is still lacking. Glycine N-methyltransferase (GNMT), a member of the family that acts on small metabolites as the substrate, catalyzes methyl transfer from S-adenosyl-l-methionine (AdoMet) to glycine to form S-adenosyl-l-homocysteine and sarcosine. We report primary carbon ((12)C/(14)C) and secondary ((1)H3/(3)H3) kinetic isotope effects at the transferred methyl group, together with (1)H3/(3)H3 binding isotope effects for wild-type GNMT and a series of Tyr21 mutants...
July 27, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27198213/possible-selection-of-host-folate-pathway-gene-polymorphisms-in-patients-with-malaria-from-a-malaria-endemic-region-in-north-east-india
#6
Darshana Mirgal, Kanjaksha Ghosh, Jagadish Mahanta, Prafulla Dutta, Shrimati Shetty
BACKGROUND: Recent studies in experimental mice have shown that mild deficiency of methylenetetrahydrofolate reductase (MTHFR) enzyme confers protection against malaria, thus providing an important basis for the hypothesis that MTHFR polymorphism, i.e. C677T, might have been subjected to selection pressure against malaria. The present study was undertaken in a malaria endemic region in North East India to assess whether a similar selection advantage exists for other genes in folate metabolism pathway...
May 2016: Transactions of the Royal Society of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/27153064/identification-of-1-2-3-4-6-penta-o-galloyl-%C3%AE-d-glucopyranoside-as-a-glycine-n-methyltransferase-enhancer-by-high-throughput-screening-of-natural-products-inhibits-hepatocellular-carcinoma
#7
Rajni Kant, Chia-Hung Yen, Chung-Kuang Lu, Ying-Chi Lin, Jih-Heng Li, Yi-Ming Arthur Chen
Glycine N-methyltransferase (GNMT) expression is vastly downregulated in hepatocellular carcinomas (HCC). High rates of GNMT knockout mice developed HCC, while overexpression of GNMT prevented aflatoxin-induced carcinogenicity and inhibited liver cancer cell proliferation. Therefore, in this study, we aimed for the identification of a GNMT inducer for HCC therapy. We established a GNMT promoter-driven luciferase reporter assay as a drug screening platform. Screening of 324 pure compounds and 480 crude extracts from Chinese medicinal herbs resulted in the identification of Paeonia lactiflora Pall (PL) extract and the active component 1,2,3,4,6-penta-O-galloyl-β-d-glucopyranoside (PGG) as a GNMT inducer...
2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27101439/global-dna-methylation-in-gonads-of-adult-zebrafish-danio-rerio-under-bisphenol-a-exposure
#8
Yan Liu, Yingying Zhang, Shiyu Tao, Yongjing Guan, Ting Zhang, Zaizhao Wang
Altered DNA methylation is pervasively associated with changes in gene expression and signal transduction after exposure to a wide range of endocrine disrupting chemicals. As a weak estrogenic chemical, bisphenol A (BPA) has been extensively studied for reproductive toxicity. In order to explore the effects of BPA on epigenetic modification in gonads of zebrafish Danio rerio, we measured the global DNA methylation together with the gene expression of DNA methyltransferase (dnmts), glycine N-methyltransferase (gnmt), and ten-eleven translocation (tets) in gonads of D...
August 2016: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/26847870/relation-of-exposure-to-amino-acids-involved-in-sarcosine-metabolic-pathway-on-behavior-of-non-tumor-and-malignant-prostatic-cell-lines
#9
Zbynek Heger, Jaromir Gumulec, Natalia Cernei, Hana Polanska, Martina Raudenska, Michal Masarik, Tomas Eckschlager, Marie Stiborova, Vojtech Adam, Rene Kizek
BACKGROUND: Sarcosine (N-methylglycine) was previously delineated as a substantial oncometabolite of prostate cancer (PCa) and its metabolism seems to be significantly involved in PCa development and behavior. METHODS: We focused on investigation whether the exposure of prostate cells (PNT1A, 22Rv1, and PC-3) to sarcosine-related amino acids (glycine, dimethylglycine, and sarcosine) affects their aggressiveness (cell mobility and division rates, using real-time cell based assay)...
May 2016: Prostate
https://www.readbyqxmd.com/read/26781304/creatine-supplementation-prevents-hyperhomocysteinemia-oxidative-stress-and-cancer-induced-cachexia-progression-in-walker-256-tumor-bearing-rats
#10
Rafael Deminice, Paola Sanches Cella, Camila S Padilha, Fernando H Borges, Lilian Eslaine Costa Mendes da Silva, Patrícia L Campos-Ferraz, Alceu Afonso Jordao, Jason Lorne Robinson, Robert F Bertolo, Rubens Cecchini, Flávia Alessandra Guarnier
The purpose of this study was to investigate (1) the impact of tumor growth on homocysteine (Hcy) metabolism, liver oxidative stress and cancer cachexia and, (2) the potential benefits of creatine supplementation in Walker-256 tumor-bearing rats. Three experiments were conducted. First, rats were killed on days 5 (D5), 10 (D10) and 14 (D14) after tumor implantation. In experiment 2, rats were randomly assigned to three groups designated as control (C), tumor-bearing (T) and tumor-bearing supplemented with creatine (TCr)...
August 2016: Amino Acids
https://www.readbyqxmd.com/read/26758245/abnormally-activated-one-carbon-metabolic-pathway-is-associated-with-mtdna-hypermethylation-and-mitochondrial-malfunction-in-the-oocytes-of-polycystic-gilt-ovaries
#11
Longfei Jia, Juan Li, Bin He, Yimin Jia, Yingjie Niu, Chenfei Wang, Ruqian Zhao
Polycystic ovarian syndrome (PCOS) is associated with hyperhomocysteinemia and polycystic ovaries (PCO) usually produce oocytes of poor quality. However, the intracellular mechanism linking hyperhomocysteinemia and oocyte quality remains elusive. In this study, the quality of the oocytes isolated from healthy and polycystic gilt ovaries was evaluated in vitro in association with one-carbon metabolism, mitochondrial DNA (mtDNA) methylation, and mitochondrial function. PCO oocytes demonstrated impaired polar body extrusion, and significantly decreased cleavage and blastocyst rates...
2016: Scientific Reports
https://www.readbyqxmd.com/read/26598833/regulation-of-folate-mediated-one-carbon-metabolism-by-glycine-n-methyltransferase-gnmt-and-methylenetetrahydrofolate-reductase-mthfr
#12
Yi-Cheng Wang, Ming-Tsung Wu, Yan-Jun Lin, Feng-Yao Tang, Hsin-An Ko, En-Pei Chiang
Folate-mediated one-carbon metabolism is an important therapeutic target of human diseases. We extensively investigated how gene-nutrient interactions may modulate human cancer risk in 2 major folate metabolic genes, MTHFR and GNMT. The biochemical impacts of MTHFR and GNMT on methyl group supply, global DNA methylation, nucleotide biosynthesis, DNA damage, and partitioning of the folate dependent 1-carbon group were carefully studied. The distinct model systems used included: EB virus-transformed lymphoblasts expressing human MTHFR polymorphic genotypes; liver-derived GNMT-null cell-lines with and without GNMT overexpression; and HepG2 cells with stabilized inhibition of MTHFR using shRNA, GNMT wildtype, heterozygotous (GNMT(het)) and knockout (GNMT(nul)) mice...
2015: Journal of Nutritional Science and Vitaminology
https://www.readbyqxmd.com/read/26527363/maternal-betaine-supplementation-during-gestation-enhances-expression-of-mtdna-encoded-genes-through-d-loop-dna-hypomethylation-in-the-skeletal-muscle-of-newborn-piglets
#13
Yimin Jia, Haogang Song, Guichao Gao, Demin Cai, Xiaojing Yang, Ruqian Zhao
Betaine has been widely used in animal and human nutrition to promote muscle growth and performance, yet it remains unknown whether maternal betaine supplementation during gestation affects the metabolic characteristics of neonatal skeletal muscles. In the present study, feeding sows with betaine-supplemented diets throughout gestation significantly upregulated the expression of mtDNA-encoded OXPHOS genes (p < 0.05), including COX1, COX2, and ND5, in the muscle of newborn piglets, which was associated with enhanced mitochondrial COX enzyme activity (p < 0...
November 25, 2015: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/26467983/mathematical-analysis-of-the-regulation-of-competing-methyltransferases
#14
Michael C Reed, Mary V Gamble, Megan N Hall, H Frederik Nijhout
BACKGROUND: Methyltransferase (MT) reactions, in which methyl groups are attached to substrates, are fundamental to many aspects of cell biology and human physiology. The universal methyl donor for these reactions is S-adenosylmethionine (SAM) and this presents the cell with an important regulatory problem. If the flux along one pathway is changed then the SAM concentration will change affecting all the other MT pathways, so it is difficult for the cell to regulate the pathways independently...
October 14, 2015: BMC Systems Biology
https://www.readbyqxmd.com/read/26429139/proteomics-analysis-of-liver-tissues-from-c57bl-6j-mice-receiving-low-dose-137cs-radiation
#15
Lan Yi, Linwei Li, Jie Yin, Nan Hu, Guangyue Li, Dexin Ding
Differentially expressed proteins in liver tissues of C57BL/6J mice receiving low-dose (137)Cs radiation were examined by proteomics analysis. Compared with the control group, 80 proteins were differentially expressed in the irradiated group. Among the 40 randomly selected proteins used for peptide mass fingerprinting analysis and bioinformatics, 24 were meaningful. These proteins were related to antioxidant defense, amino acid metabolism, detoxification, anti-tumor development, amino acid transport, anti-peroxidation, and composition of respiratory chain...
February 2016: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/26419525/gestation-under-chronic-constant-light-leads-to-extensive-gene-expression-changes-in-the-fetal-rat-liver
#16
Carlos Spichiger, Claudia Torres-Farfan, Hugo A Galdames, Natalia Mendez, Pamela Alonso-Vazquez, Hans G Richter
Recent reports account for altered metabolism in adult offspring from pregnancy subjected to abnormal photoperiod, suggesting fetal programming of liver physiology. To generate a pipeline of subsequent mechanistic experiments addressing strong candidate genes, here we investigated the effects of constant gestational light on the fetal liver transcriptome. At 10 days of gestation, dams were randomized in two groups (n = 7 each): constant light (LL) and normal photoperiod (12 h light/12 h dark; LD). At 18 days of gestation, RNA was isolated from the fetal liver and subjected to DNA microarray (Affymetrix platform for 28,000 genes)...
December 2015: Physiological Genomics
https://www.readbyqxmd.com/read/26394163/methionine-and-s-adenosylmethionine-levels-are-critical-regulators-of-pp2a-activity-modulating-lipophagy-during-steatosis
#17
Imanol Zubiete-Franco, Juan Luis García-Rodríguez, Maite Martínez-Uña, Nuria Martínez-Lopez, Ashwin Woodhoo, Virginia Gutiérrez-De Juan, Naiara Beraza, Sergio Lage-Medina, Fernando Andrade, Marta Llarena Fernandez, Luis Aldámiz-Echevarría, David Fernández-Ramos, Juan Manuel Falcon-Perez, Fernando Lopitz-Otsoa, Pablo Fernandez-Tussy, Lucía Barbier-Torres, Zigmund Luka, Conrad Wagner, Carmelo García-Monzón, Shelly C Lu, Patricia Aspichueta, José María Mato, María Luz Martínez-Chantar, Marta Varela-Rey
BACKGROUND & AIMS: Glycine N-methyltransferase (GNMT) expression is decreased in some patients with severe non-alcoholic fatty liver disease. Gnmt deficiency in mice (Gnmt-KO) results in abnormally elevated serum levels of methionine and its metabolite S-adenosylmethionine (SAMe), and this leads to rapid liver steatosis development. Autophagy plays a critical role in lipid catabolism (lipophagy), and defects in autophagy have been related to liver steatosis development. Since methionine and its metabolite SAMe are well known inactivators of autophagy, we aimed to examine whether high levels of both metabolites could block autophagy-mediated lipid catabolism...
February 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/26383889/enhancing-s-adenosyl-methionine-catabolism-extends-drosophila-lifespan
#18
Fumiaki Obata, Masayuki Miura
Methionine restriction extends the lifespan of various model organisms. Limiting S-adenosyl-methionine (SAM) synthesis, the first metabolic reaction of dietary methionine, extends longevity in Caenorhabditis elegans but accelerates pathology in mammals. Here, we show that, as an alternative to inhibiting SAM synthesis, enhancement of SAM catabolism by glycine N-methyltransferase (Gnmt) extends the lifespan in Drosophila. Gnmt strongly buffers systemic SAM levels by producing sarcosine in either high-methionine or low-sams conditions...
2015: Nature Communications
https://www.readbyqxmd.com/read/26339363/expression-of-sarcosine-metabolism-related-proteins-in-estrogen-receptor-negative-breast-cancer-according-to-the-androgen-receptor-and-her-2-status
#19
Min Ju Kim, Woo Hee Jung, Ja Seung Koo
The aim of this study is to investigate the expression of sarcosine metabolism related proteins according to androgen receptor (AR) and HER-2 status in estrogen receptor (ER) negative breast cancer and to analyze its clinical implications. Tissue microarray was constructed for a total of 334 cases of ER negative breast cancer. Immunohistochemical stain was conducted for sarcosine metabolism related proteins such as glycine N-methyltransferase (GNMT), sarcosine dehydrogenase (SARDH), and l-pipecolic acid oxidase (PIPOX)...
2015: International Journal of Clinical and Experimental Pathology
https://www.readbyqxmd.com/read/26322888/dysregulated-hepatic-methionine-metabolism-drives-homocysteine-elevation-in-diet-induced-nonalcoholic-fatty-liver-disease
#20
Tommy Pacana, Sophie Cazanave, Aurora Verdianelli, Vaishali Patel, Hae-Ki Min, Faridoddin Mirshahi, Eoin Quinlivan, Arun J Sanyal
Methionine metabolism plays a central role in methylation reactions, production of glutathione and methylarginines, and modulating homocysteine levels. The mechanisms by which these are affected in NAFLD are not fully understood. The aim is to perform a metabolomic, molecular and epigenetic analyses of hepatic methionine metabolism in diet-induced NAFLD. Female 129S1/SvlmJ;C57Bl/6J mice were fed a chow (n = 6) or high-fat high-cholesterol (HFHC) diet (n = 8) for 52 weeks. Metabolomic study, enzymatic expression and DNA methylation analyses were performed...
2015: PloS One
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