Base de dados : MEDLINE
Pesquisa : D08.811.913.555.500.650 [Categoria DeCS]
Referências encontradas : 117 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 12 ir para página                         

  1 / 117 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
[PMID]:29277772
[Au] Autor:Ishibashi K; Ishii K; Sugiyama G; Sumida T; Sugiura T; Kamata YU; Seki K; Fujinaga T; Kumamaru W; Kobayashi Y; Hiyake N; Nakano H; Yamada T; Mori Y
[Ad] Endereço:Section of Oral & Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
[Ti] Título:Deregulation of Nicotinamide N-Methyltransferase and Gap Junction Protein Alpha-1 Causes Metastasis in Adenoid Cystic Carcinoma.
[So] Source:Anticancer Res;38(1):187-197, 2018 01.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIM: Adenoid cystic carcinoma (AdCC) is a malignant tumor that occurs in the salivary glands and frequently metastasizes. The aim of this study was to identify factors mediating AdCC metastasis. MATERIALS AND METHODS: We established three AdCC cell lines by orthotropic transplantation and in vivo selection: parental, highly metastatic (ACCS-M-GFP), and lymph node metastatic (ACCS-LN-GFP) cells. RESULTS: We examined the three cell lines. DNA microarray indicated significantly altered processes in ACCS-LN-GFP cells: particularly, the expression of nicotinamide N-methyltransferase (NNMT) was enhanced the most. NNMT is associated with tumorigenesis and is a potential tumor biomarker. Concomitantly, we found-significant down-regulation of gap junction protein alpha-1. We suggest that ACCS-LN-GFP cells acquire cancer stem cell features involving the up-regulation of NNMT and the loss of gap junction protein alpha-1, leading to epithelial-mesenchymal transition and consequent AdCC metastasis. CONCLUSION: NNMT is a potential biomarker of AdCC.
[Mh] Termos MeSH primário: Carcinoma Adenoide Cístico/patologia
Conexina 43/metabolismo
Nicotinamida N-Metiltransferase/metabolismo
Neoplasias das Glândulas Salivares/patologia
[Mh] Termos MeSH secundário: Animais
Carcinoma Adenoide Cístico/metabolismo
Linhagem Celular Tumoral
Movimento Celular
Proliferação Celular
Feminino
Seres Humanos
Camundongos Nus
Neoplasias das Glândulas Salivares/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Connexin 43); 0 (GJA1 protein, mouse); EC 2.1.1.1 (Nicotinamide N-Methyltransferase)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180105
[Lr] Data última revisão:
180105
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171227
[St] Status:MEDLINE


  2 / 117 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28720493
[Au] Autor:Swaminathan S; Birudukota S; Thakur MK; Parveen R; Kandan S; Juluri S; Shaik S; Anand NN; Burri RR; Kristam R; Hallur MS; Rajagopal S; Schreuder H; Langer T; Rudolph C; Ruf S; Dhakshinamoorthy S; Gosu R; Kannt A
[Ad] Endereço:Department of Structural Biology, Jubilant Biosys Ltd, Bangalore 560022, India.
[Ti] Título:Crystal structures of monkey and mouse nicotinamide N-methyltransferase (NNMT) bound with end product, 1-methyl nicotinamide.
[So] Source:Biochem Biophys Res Commun;491(2):416-422, 2017 Sep 16.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Nicotinamide N-methyltransferase (NNMT) is a S-adenosyl-l-methionine (SAM)-dependent enzyme that catalyzes N-methylation of nicotinamide (NA) and other pyridines to form N-methyl pyridinium ions. Here we report the first ternary complex X-ray crystal structures of monkey NNMT and mouse NNMT in bound form with the primary endogenous product, 1-methyl nicotinamide (MNA) and demethylated cofactor, S-adenosyl-homocysteine (SAH) determined at 2.30 Å and 1.88 Å respectively. The structural fold of these enzymes is identical to human NNMT. It is known that the primary endogenous product catalyzed by NNMT, MNA is a specific inhibitor of NNMT. Our data clearly indicates that the MNA binds to the active site and it would be trapped in the active site due to the formation of the bridge between the pole (long helix, α3) and long C-terminal loop. This might explain the mechanism of MNA acting as a feedback inhibitor of NNMT.
[Mh] Termos MeSH primário: Retroalimentação Fisiológica
Niacinamida/análogos & derivados
Nicotinamida N-Metiltransferase/química
S-Adenosilmetionina/química
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Domínio Catalítico
Clonagem Molecular
Cristalografia por Raios X
Escherichia coli/genética
Escherichia coli/metabolismo
Expressão Gênica
Macaca mulatta
Camundongos
Modelos Moleculares
Niacinamida/química
Niacinamida/metabolismo
Nicotinamida N-Metiltransferase/antagonistas & inibidores
Nicotinamida N-Metiltransferase/genética
Nicotinamida N-Metiltransferase/metabolismo
Ligação Proteica
Conformação Proteica em alfa-Hélice
Conformação Proteica em Folha beta
Domínios e Motivos de Interação entre Proteínas
Estrutura Terciária de Proteína
Proteínas Recombinantes/química
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
S-Adenosilmetionina/metabolismo
Alinhamento de Sequência
Homologia de Sequência de Aminoácidos
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Recombinant Proteins); 25X51I8RD4 (Niacinamide); 7LP2MPO46S (S-Adenosylmethionine); EC 2.1.1.1 (Nicotinamide N-Methyltransferase); UM47085BXC (N(1)-methylnicotinamide)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170829
[Lr] Data última revisão:
170829
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170720
[St] Status:MEDLINE


  3 / 117 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28548833
[Au] Autor:Neelakantan H; Wang HY; Vance V; Hommel JD; McHardy SF; Watowich SJ
[Ad] Endereço:Department of Biochemistry and Molecular Biology, University of Texas Medical Branch , Galveston, Texas 77550 United States.
[Ti] Título:Structure-Activity Relationship for Small Molecule Inhibitors of Nicotinamide N-Methyltransferase.
[So] Source:J Med Chem;60(12):5015-5028, 2017 Jun 22.
[Is] ISSN:1520-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Nicotinamide N-methyltransferase (NNMT) is a fundamental cytosolic biotransforming enzyme that catalyzes the N-methylation of endogenous and exogenous xenobiotics. We have identified small molecule inhibitors of NNMT with >1000-fold range of activity and developed comprehensive structure-activity relationships (SARs) for NNMT inhibitors. Screening of N-methylated quinolinium, isoquinolinium, pyrididium, and benzimidazolium/benzothiazolium analogues resulted in the identification of quinoliniums as a promising scaffold with very low micromolar (IC ∼ 1 µM) NNMT inhibition. Computer-based docking of inhibitors to the NNMT substrate (nicotinamide)-binding site produced a robust correlation between ligand-enzyme interaction docking scores and experimentally calculated IC values. Predicted binding orientation of the quinolinium analogues revealed selective binding to the NNMT substrate-binding site residues and essential chemical features driving protein-ligand intermolecular interactions and NNMT inhibition. The development of this new series of small molecule NNMT inhibitors direct the future design of lead drug-like inhibitors to treat several metabolic and chronic disease conditions characterized by abnormal NNMT activity.
[Mh] Termos MeSH primário: Inibidores Enzimáticos/química
Inibidores Enzimáticos/farmacologia
Nicotinamida N-Metiltransferase/antagonistas & inibidores
Bibliotecas de Moléculas Pequenas/farmacologia
Relação Estrutura-Atividade
[Mh] Termos MeSH secundário: Sítios de Ligação
Seres Humanos
Concentração Inibidora 50
Espectroscopia de Ressonância Magnética
Simulação de Acoplamento Molecular
Nicotinamida N-Metiltransferase/genética
Nicotinamida N-Metiltransferase/metabolismo
Bibliotecas de Moléculas Pequenas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (Small Molecule Libraries); EC 2.1.1.1 (Nicotinamide N-Methyltransferase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170811
[Lr] Data última revisão:
170811
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170527
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jmedchem.7b00389


  4 / 117 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28420001
[Au] Autor:Li Q; He MD; Mao L; Wang X; Jiang YL; Li M; Lu YH; Yu ZP; Zhou Z
[Ad] Endereço:Department of Occupational Health, Nanning, China.
[Ti] Título:Nicotinamide N-Methyltransferase Suppression Participates in Nickel-Induced Histone H3 Lysine9 Dimethylation in BEAS-2B Cells.
[So] Source:Cell Physiol Biochem;41(5):2016-2026, 2017.
[Is] ISSN:1421-9778
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Nickel compounds are well-established human carcinogens with weak mutagenic activity. Histone methylation has been proposed to play an important role in nickel-induced carcinogenesis. Nicotinamide N-methyltransferase (NNMT) decreases histone methylation in several cancer cells by altering the cellular ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH). However, the role of NNMT in nickel-induced histone methylation remains unclear. METHODS: BEAS-2B cells were exposed to different concentrations of nickel chloride (NiCl2) for 72 h or 200 µM NiCl2 for different time periods. Histone H3 on lysine 9 (H3K9) mono-, di-, and trimethylation and NNMT protein levels were measured by western blot analysis. Expressions of NNMT mRNA and the H3k9me2-associated genes, mitogen-activated protein kinase 3 (MAP2K3) and dickkopf1 (DKK1), were determined by qPCR analysis. The cellular ratio of nicotinamide adenine dinucleotide (NAD+) to reduced NAD (NADH) and SAM/SAH ratio were determined. RESULTS: Exposure of BEAS-2B cells to nickel increased H3K9 dimethylation (H3K9me2), suppressed the expressions of H3K9me2-associated genes (MAP2K3 and DKK1), and induced NNMT repression at both the protein and mRNA levels. Furthermore, over-expression of NNMT inhibited nickel-induced H3K9me2 and altered the cellular SAM/SAH ratio. Additionally, the NADH oxidant phenazine methosulfate (PMS) not only reversed the nickel-induced reduction in NAD+/NADH but also inhibited the increase in H3K9me2. CONCLUSIONS: These findings indicate that the repression of NNMT may underlie nickel-induced H3K9 dimethylation by altering the cellular SAM/SAH ratio.
[Mh] Termos MeSH primário: Histonas/metabolismo
Níquel/farmacologia
Nicotinamida N-Metiltransferase/metabolismo
S-Adenosil-Homocisteína/metabolismo
S-Adenosilmetionina/metabolismo
[Mh] Termos MeSH secundário: Linhagem Celular
Histonas/genética
Seres Humanos
Peptídeos e Proteínas de Sinalização Intercelular/genética
Peptídeos e Proteínas de Sinalização Intercelular/metabolismo
MAP Quinase Quinase 3/genética
MAP Quinase Quinase 3/metabolismo
Metilação/efeitos dos fármacos
Nicotinamida N-Metiltransferase/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DKK1 protein, human); 0 (Histones); 0 (Intercellular Signaling Peptides and Proteins); 696BNE976J (nickel chloride); 7LP2MPO46S (S-Adenosylmethionine); 7OV03QG267 (Nickel); 979-92-0 (S-Adenosylhomocysteine); EC 2.1.1.1 (NNMT protein, human); EC 2.1.1.1 (Nicotinamide N-Methyltransferase); EC 2.7.12.2 (MAP Kinase Kinase 3); EC 2.7.12.2 (MAP2K3 protein, human)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170623
[Lr] Data última revisão:
170623
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170419
[St] Status:MEDLINE
[do] DOI:10.1159/000475432


  5 / 117 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28121423
[Au] Autor:Neelakantan H; Vance V; Wang HL; McHardy SF; Watowich SJ
[Ad] Endereço:Department of Biochemistry and Molecular Biology, University of Texas Medical Branch , Galveston, Texas 77555, United States.
[Ti] Título:Noncoupled Fluorescent Assay for Direct Real-Time Monitoring of Nicotinamide N-Methyltransferase Activity.
[So] Source:Biochemistry;56(6):824-832, 2017 Feb 14.
[Is] ISSN:1520-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Nicotinamide N-methyltransferase (NNMT) is an important biotransforming enzyme that catalyzes the transfer of a labile methyl group from the ubiquitous cofactor S-5'-adenosyl-l-methionine (SAM) to endogenous and exogenous small molecules to form methylated end products. NNMT has been implicated in a number of chronic disease conditions, including metabolic disorders, cardiovascular disease, cancer, osteoarthritis, kidney disease, and Parkinson's disease. We have developed a novel noncoupled fluorescence-based methyltransferase assay that allows direct ultrasensitive real-time detection of the NNMT reaction product 1-methylquinolinium. This is the first assay reported to date to utilize fluorescence spectroscopy to directly monitor NNMT product formation and activity in real time. This assay provided accurate kinetic data that allowed detailed comparative analysis of the NNMT reaction mechanism and kinetic parameters. A reaction model based on a random bireactant mechanism produced global curve fits that were most consistent with steady-state initial velocity data collected across an array of substrate concentrations. On the basis of the reaction mechanism, each substrate could independently bind to the NNMT apoenzyme; however, both substrates bound to the complementary binary complexes with an affinity ∼20-fold stronger compared to their binding to the apoenzyme. This reaction mechanism implies either substrate-induced conformational changes or bireactant intermolecular interactions may stabilize the binding of the substrate to the binary complex and formation of the ternary complex. Importantly, this assay could rapidly generate concentration response curves for known NNMT inhibitors, suggesting its applicability for high-throughput screening of chemical libraries to identify novel NNMT inhibitors. Furthermore, our novel assay potentially offers a robust detection technology for use in SAM substrate competition assays for the discovery and development of SAM-dependent methyltransferase inhibitors.
[Mh] Termos MeSH primário: Modelos Moleculares
Nicotinamida N-Metiltransferase/metabolismo
[Mh] Termos MeSH secundário: Apoenzimas/antagonistas & inibidores
Apoenzimas/química
Apoenzimas/genética
Apoenzimas/metabolismo
Biocatálise/efeitos dos fármacos
Calibragem
Inibidores Enzimáticos/farmacologia
Ensaios de Triagem em Larga Escala
Seres Humanos
Limite de Detecção
Metilação/efeitos dos fármacos
Nicotinamida N-Metiltransferase/antagonistas & inibidores
Nicotinamida N-Metiltransferase/química
Nicotinamida N-Metiltransferase/genética
Conformação Proteica
Redobramento de Proteína/efeitos dos fármacos
Compostos de Quinolínio/metabolismo
Proteínas Recombinantes/química
Proteínas Recombinantes/isolamento & purificação
Proteínas Recombinantes/metabolismo
Reprodutibilidade dos Testes
S-Adenosilmetionina/metabolismo
Espectrometria de Fluorescência
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Apoenzymes); 0 (Enzyme Inhibitors); 0 (Quinolinium Compounds); 0 (Recombinant Proteins); 21979-19-1 (1-methylquinolinium); 7LP2MPO46S (S-Adenosylmethionine); EC 2.1.1.1 (NNMT protein, human); EC 2.1.1.1 (Nicotinamide N-Methyltransferase)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170516
[Lr] Data última revisão:
170516
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170126
[St] Status:MEDLINE
[do] DOI:10.1021/acs.biochem.6b01215


  6 / 117 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27999813
[Au] Autor:Zhu XJ; Lin YJ; Chen W; Wang YH; Qiu LQ; Cai CX; Xiong Q; Chen F; Chen LH; Zhou Q; Li JH
[Ad] Endereço:Key Lab of Training, Monitoring and Intervention of Aquatic Sports of General Administration of Sport of China, Institute of Physical Education, Jiangxi Normal University, Nanchang, China.
[Ti] Título:Physiological Study on Association between Nicotinamide N-Methyltransferase Gene Polymorphisms and Hyperlipidemia.
[So] Source:Biomed Res Int;2016:7521942, 2016.
[Is] ISSN:2314-6141
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Nicotinamide N-methyltransferase (NNMT) catalyzes the methylation of nicotinamide. Our previous works indicate that NNMT is involved in the body mass index and energy metabolism, and recently the association between a SNP (rs694539) of and a variety of cardiovascular diseases was reported. At present, more than 200 single nucleotide polymorphisms (SNPs) have been identified in the databases of the human genome projects; however, the association between rs694539 variation and hyperlipidemia has not been reported yet, and whether there are any SNPs in significantly associated with hyperlipidemia is still unclear. In this paper, we selected 19 SNPs in as the tagSNPs using Haploview software (Haploview 4.2) first and then performed a case-control study to observe the association between these tagSNPs and hyperlipidemia and finally applied physiological approaches to explore the possible mechanisms through which the polymorphism induces hyperlipidemia. The results show that a SNP (rs1941404) in is significantly associated with hyperlipidemia, and the influence of rs1941404 variation on the resting energy expenditure may be the possible mechanism for rs1941404 variation to induce hyperlipidemia.
[Mh] Termos MeSH primário: Bases de Dados Genéticas
Metabolismo Energético/genética
Hiperlipidemias
Nicotinamida N-Metiltransferase
Polimorfismo de Nucleotídeo Único
Software
[Mh] Termos MeSH secundário: Adulto
Idoso
Feminino
Seres Humanos
Hiperlipidemias/enzimologia
Hiperlipidemias/genética
Hiperlipidemias/fisiopatologia
Masculino
Meia-Idade
Nicotinamida N-Metiltransferase/genética
Nicotinamida N-Metiltransferase/metabolismo
[Pt] Tipo de publicação:CLINICAL TRIAL; JOURNAL ARTICLE
[Nm] Nome de substância:
EC 2.1.1.1 (NNMT protein, human); EC 2.1.1.1 (Nicotinamide N-Methyltransferase)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170224
[Lr] Data última revisão:
170224
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161222
[St] Status:MEDLINE
[do] DOI:10.1155/2016/7521942


  7 / 117 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
[PMID]:27726107
[Au] Autor:Sazci A; Sazci G; Sazci B; Ergul E; Idrisoglu HA
[Ad] Endereço:Department of Medical Biology and Genetics, Faculty of Medicine, University of Kocaeli, Kocaeli, 41380, Turkey. alisazci@gmail.com.
[Ti] Título:Nicotinamide-N-Methyltransferase gene rs694539 variant and migraine risk.
[So] Source:J Headache Pain;17(1):93, 2016 Dec.
[Is] ISSN:1129-2377
[Cp] País de publicação:Italy
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Migraine is a common neurovascular disorder affecting 10 to 20 % of the world population usually subdivided into migraine with auro (MA) and migraine without auro (MO). Homocysteine is involved in the pathophysiology of a number of neurological disorders. Elevated levels of homocysteine in the plasma is produced by the MTHFR gene rs 1801133 and rs 1801131 variants as well as the NNMT gene rs 694539 variant. METHODS: With the polymerase chain reaction-restriction fragment length polymorphism method developed recently in our laboratory, we were able to show an association between the NNMT gene rs694539 variant and migraine for the first time. RESULTS: Here we report the association of the Nicotinamide-N-methyltransferase gene (NNMT) rs694539 variant with migraine in a case-control study of 433 patients with migraine and 229 healthy controls (χ2 = 6.076, P = 0.048). After stratification, we were able only to show an association between the NNMT gene rs694539 variant and female patients with migraine on the genotype and allelic levels. However there was no association in male patients with migraine (χ2 = 1.054, P = 0.590). CONCLUSIONS: Consequently our results clearly indicate that the NNMT gene rs694539 variant is a genetic risk factor for migraine.
[Mh] Termos MeSH primário: Transtornos de Enxaqueca/genética
Nicotinamida N-Metiltransferase/genética
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Idoso de 80 Anos ou mais
Alelos
Estudos de Casos e Controles
Feminino
Predisposição Genética para Doença
Genótipo
Seres Humanos
Masculino
Meia-Idade
Polimorfismo de Nucleotídeo Único
Risco
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 2.1.1.1 (NNMT protein, human); EC 2.1.1.1 (Nicotinamide N-Methyltransferase)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161012
[St] Status:MEDLINE


  8 / 117 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27592202
[Au] Autor:Drew JE; Farquharson AJ; Horgan GW; Williams LM
[Ad] Endereço:Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen AB21 9SB, Scotland. Electronic address: j.drew@abdn.ac.uk.
[Ti] Título:Tissue-specific regulation of sirtuin and nicotinamide adenine dinucleotide biosynthetic pathways identified in C57Bl/6 mice in response to high-fat feeding.
[So] Source:J Nutr Biochem;37:20-29, 2016 11.
[Is] ISSN:1873-4847
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The sirtuin (SIRT)/nicotinamide adenine dinucleotide (NAD) system is implicated in development of type 2 diabetes (T2D) and diet-induced obesity, a major risk factor for T2D. Mechanistic links have not yet been defined. SIRT/NAD system gene expression and NAD/NADH levels were measured in liver, white adipose tissue (WAT) and skeletal muscle from mice fed either a low-fat diet or high-fat diet (HFD) for 3 days up to 16 weeks. An in-house custom-designed multiplex gene expression assay assessed all 7 mouse SIRTs (SIRT1-7) and 16 enzymes involved in conversion of tryptophan, niacin, nicotinamide riboside and metabolic precursors to NAD. Significantly altered transcription was correlated with body weight, fat mass, plasma lipids and hormones. Regulation of the SIRT/NAD system was associated with early (SIRT4, SIRT7, NAPRT1 and NMNAT2) and late phases (NMNAT3, NMRK2, ABCA1 and CD38) of glucose intolerance. TDO2 and NNMT were identified as markers of HFD consumption. Altered regulation of the SIRT/NAD system in response to HFD was prominent in liver compared with WAT or muscle. Multiple components of the SIRTs and NAD biosynthetic enzymes network respond to consumption of dietary fat. Novel molecular targets identified above could direct strategies for dietary/therapeutic interventions to limit metabolic dysfunction and development of T2D.
[Mh] Termos MeSH primário: Regulação Enzimológica da Expressão Gênica
Fígado/enzimologia
Proteínas Mitocondriais/metabolismo
Nicotinamida N-Metiltransferase/metabolismo
Obesidade/metabolismo
Sirtuínas/metabolismo
Triptofano Oxigenase/metabolismo
[Mh] Termos MeSH secundário: Tecido Adiposo Branco/enzimologia
Tecido Adiposo Branco/metabolismo
Adiposidade
Animais
Biomarcadores/sangue
Biomarcadores/metabolismo
Dieta Hiperlipídica/efeitos adversos
Intolerância à Glucose/sangue
Intolerância à Glucose/etiologia
Intolerância à Glucose/metabolismo
Fígado/metabolismo
Masculino
Camundongos Endogâmicos C57BL
Proteínas Mitocondriais/genética
Músculo Esquelético/enzimologia
Músculo Esquelético/metabolismo
NAD/biossíntese
Nicotinamida N-Metiltransferase/genética
Obesidade/sangue
Obesidade/etiologia
Especificidade de Órgãos
Análise de Componente Principal
Sirtuínas/genética
Triptofano Oxigenase/genética
Ganho de Peso
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Biomarkers); 0 (Mitochondrial Proteins); 0 (Sirt7 protein, mouse); 0U46U6E8UK (NAD); EC 1.13.11.11 (Tryptophan Oxygenase); EC 2.1.1.1 (Nicotinamide N-Methyltransferase); EC 2.1.1.1 (Nnmt protein, mouse); EC 3.5.1.- (SIRT4 protein, mouse); EC 3.5.1.- (Sirtuins)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171109
[Lr] Data última revisão:
171109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160905
[St] Status:MEDLINE


  9 / 117 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27570878
[Au] Autor:van Haren MJ; Sastre Toraño J; Sartini D; Emanuelli M; Parsons RB; Martin NI
[Ad] Endereço:Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University , Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
[Ti] Título:A Rapid and Efficient Assay for the Characterization of Substrates and Inhibitors of Nicotinamide N-Methyltransferase.
[So] Source:Biochemistry;55(37):5307-15, 2016 Sep 20.
[Is] ISSN:1520-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Nicotinamide N-methyltransferase (NNMT) is one of the most abundant small molecule methyltransferases in the human body and is primarily responsible for the N-methylation of the nicotinamide (vitamin B3). Employing the cofactor S-adenosyl-l-methionine, NNMT transfers a methyl group to the pyridine nitrogen of nicotinamide to generate N-methylnicotinamide. Interestingly, NNMT is also able to N-methylate a variety of other pyridine-containing small molecules, suggesting a secondary role for the enzyme in the detoxification of xenobiotics. A number of recent studies have also revealed links between NNMT overexpression and a variety of diseases, including multiple cancers, Parkinson's disease, diabetes, and obesity. To facilitate further study of both the substrate scope and potential for inhibitor development, we here describe the development of a new NNMT activity assay. The assay makes use of ultra-high-performance hydrophilic interaction chromatography, allowing for rapid separation of the reaction products, coupled with quadrupole time-of-flight mass spectrometric detection, providing for enhanced sensitivity and enabling high-throughput sample analysis. We successfully demonstrated the general applicability of the method by performing kinetic analyses of NNMT-mediated methylation for a range of pyridine-based substrates. These findings also provide new insight into the diversity of substrate recognition by NNMT in a quantitative manner. In addition, we further established the suitability of the assay for the identification and characterization of small molecule inhibitors of NNMT. To do so, we investigated the inhibition of NNMT by the nonspecific methyltransferase inhibitors sinefungin and S-adenosyl-l-homocysteine, revealing IC50 values in the low micromolar range. The results of these inhibition studies are particularly noteworthy as they will permit future efforts toward the development of new NNMT-specific inhibitors.
[Mh] Termos MeSH primário: Nicotinamida N-Metiltransferase/metabolismo
[Mh] Termos MeSH secundário: Seres Humanos
Nicotinamida N-Metiltransferase/antagonistas & inibidores
Nicotinamida N-Metiltransferase/genética
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Recombinant Proteins); EC 2.1.1.1 (Nicotinamide N-Methyltransferase)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170510
[Lr] Data última revisão:
170510
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160830
[St] Status:MEDLINE
[do] DOI:10.1021/acs.biochem.6b00733


  10 / 117 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27389312
[Au] Autor:Thomas MG; Sartini D; Emanuelli M; van Haren MJ; Martin NI; Mountford DM; Barlow DJ; Klamt F; Ramsden DB; Reza M; Parsons RB
[Ad] Endereço:Institute of Pharmaceutical Science, King's College London, London SE1 9NH, U.K.
[Ti] Título:Nicotinamide N-methyltransferase catalyses the N-methylation of the endogenous ß-carboline norharman: evidence for a novel detoxification pathway.
[So] Source:Biochem J;473(19):3253-67, 2016 Oct 01.
[Is] ISSN:1470-8728
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Nicotinamide N-methyltransferase (NNMT) is responsible for the N-methylation of nicotinamide to 1-methylnicotinamide. Our recent studies have demonstrated that NNMT regulates cellular processes fundamental to the correct functioning and survival of the cell. It has been proposed that NNMT may possess ß-carboline (BC) N-methyltransferase activity, endogenously and exogenously produced pyridine-containing compounds which, when N-methylated, are potent inhibitors of Complex I and have been proposed to have a role in the pathogenesis of Parkinson's disease. We have investigated the ability of recombinant NNMT to N-methylate norharman (NH) to 2-N-methylnorharman (MeNH). In addition, we have investigated the toxicity of the BC NH, its precursor 1,2,3,4-tetrahydronorharman (THNH) and its N-methylated metabolite MeNH, using our in vitro SH-SY5Y NNMT expression model. Recombinant NNMT demonstrated NH 2N-methyltransferase activity, with a Km of 90 ± 20 µM, a kcat of 3 × 10(-4) ± 2 × 10(-5) s(-1) and a specificity constant (kcat/Km) of 3 ± 1 s(-1) M(-1) THNH was the least toxic of all three compounds investigated, whereas NH demonstrated the greatest, with no difference observed in terms of cell viability and cell death between NNMT-expressing and non-expressing cells. In NNMT-expressing cells, MeNH increased cell viability and cellular ATP concentration in a dose-dependent manner after 72 and 120 h incubation, an effect that was not observed after 24 h incubation or in non-NNNT-expressing cells at any time point. Taken together, these results suggest that NNMT may be a detoxification pathway for BCs such as NH.
[Mh] Termos MeSH primário: Carbolinas/metabolismo
Nicotinamida N-Metiltransferase/metabolismo
[Mh] Termos MeSH secundário: Catálise
Linhagem Celular Tumoral
Seres Humanos
Metilação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carbolines); 94HMA1I78O (norharman); EC 2.1.1.1 (Nicotinamide N-Methyltransferase)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170627
[Lr] Data última revisão:
170627
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160709
[St] Status:MEDLINE
[do] DOI:10.1042/BCJ20160219



página 1 de 12 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde