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  1 / 25237 MEDLINE  
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[PMID]:28970007
[Au] Autor:Preissler J; Wahlefeld S; Lorent C; Teutloff C; Horch M; Lauterbach L; Cramer SP; Zebger I; Lenz O
[Ad] Endereço:Technische Universität Berlin, Institut für Chemie, Sekr. PC14, Straße des 17. Juni 135, D-10623 Berlin, Germany.
[Ti] Título:Enzymatic and spectroscopic properties of a thermostable [NiFe]­hydrogenase performing H -driven NAD -reduction in the presence of O .
[So] Source:Biochim Biophys Acta;1859(1):8-18, 2018 01.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Biocatalysts that mediate the H -dependent reduction of NAD to NADH are attractive from both a fundamental and applied perspective. Here we present the first biochemical and spectroscopic characterization of an NAD -reducing [NiFe]­hydrogenase that sustains catalytic activity at high temperatures and in the presence of O , which usually acts as an inhibitor. We isolated and sequenced the four structural genes, hoxFUYH, encoding the soluble NAD -reducing [NiFe]­hydrogenase (SH) from the thermophilic betaproteobacterium, Hydrogenophilus thermoluteolus TH-1 (Ht). The HtSH was recombinantly overproduced in a hydrogenase-free mutant of the well-studied, H -oxidizing betaproteobacterium Ralstonia eutropha H16 (Re). The enzyme was purified and characterized with various biochemical and spectroscopic techniques. Highest H -mediated NAD reduction activity was observed at 80°C and pH6.5, and catalytic activity was found to be sustained at low O concentrations. Infrared spectroscopic analyses revealed a spectral pattern for as-isolated HtSH that is remarkably different from those of the closely related ReSH and other [NiFe]­hydrogenases. This indicates an unusual configuration of the oxidized catalytic center in HtSH. Complementary electron paramagnetic resonance spectroscopic analyses revealed spectral signatures similar to related NAD -reducing [NiFe]­hydrogenases. This study lays the groundwork for structural and functional analyses of the HtSH as well as application of this enzyme for H -driven cofactor recycling under oxic conditions at elevated temperatures.
[Mh] Termos MeSH primário: Proteínas de Bactérias/química
Cupriavidus necator/enzimologia
Temperatura Alta
Hidrogênio/química
Hidrogenase/química
Hydrogenophilaceae/enzimologia
NAD/química
[Mh] Termos MeSH secundário: Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Cupriavidus necator/genética
Estabilidade Enzimática
Hidrogênio/metabolismo
Hidrogenase/genética
Hidrogenase/metabolismo
Hydrogenophilaceae/genética
NAD/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Bacterial Proteins); 0U46U6E8UK (NAD); 7YNJ3PO35Z (Hydrogen); EC 1.12.- (nickel-iron hydrogenase); EC 1.12.7.2 (Hydrogenase)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171004
[St] Status:MEDLINE


  2 / 25237 MEDLINE  
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[PMID]:28470513
[Au] Autor:Präbst K; Engelhardt H; Ringgeler S; Hübner H
[Ad] Endereço:Institute of Bioprocess Engineering, Friedrich-Alexander University Erlangen-Nürnberg, Paul-Gordan-Str. 3, 91052, Erlangen, Germany. konstantin.praebst@fau.de.
[Ti] Título:Basic Colorimetric Proliferation Assays: MTT, WST, and Resazurin.
[So] Source:Methods Mol Biol;1601:1-17, 2017.
[Is] ISSN:1940-6029
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:This chapter describes selected assays for the evaluation of cellular viability and proliferation of cell cultures. The underlying principle of these assays is the measurement of a biochemical marker to evaluate the cell's metabolic activity. The formation of the omnipresent reducing agents NADH and NADPH is used as a marker for metabolic activity in the following assays. Using NADH and NADPH as electron sources, specific dyes are biochemically reduced which results in a color change that can be determined with basic photometrical methods. The assays selected for this chapter include MTT, WST, and resazurin. They are applicable for adherent or suspended cell lines, easy to perform, and comparably economical. Detailed protocols and notes for easier handling and avoiding pitfalls are enclosed to each assay.
[Mh] Termos MeSH primário: Contagem de Células/métodos
Proliferação Celular
Sobrevivência Celular
Colorimetria/métodos
Indicadores e Reagentes/química
Oxazinas/química
Sais de Tetrazólio/química
Tiazóis/química
Xantenos/química
[Mh] Termos MeSH secundário: Bioensaio
Calibragem
Células HeLa
Seres Humanos
NAD/análise
NADP/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H tetrazolium monosodium salt); 0 (Indicators and Reagents); 0 (Oxazines); 0 (Tetrazolium Salts); 0 (Thiazoles); 0 (Xanthenes); 0U46U6E8UK (NAD); 1FN9YD6968 (resazurin); 53-59-8 (NADP); EUY85H477I (thiazolyl blue)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180219
[Lr] Data última revisão:
180219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1007/978-1-4939-6960-9_1


  3 / 25237 MEDLINE  
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[PMID]:28449683
[Au] Autor:Wang LF; Wang XN; Huang CC; Hu L; Xiao YF; Guan XH; Qian YS; Deng KY; Xin HB
[Ad] Endereço:Institute of Translational Medicine, Nanchang University, 999 Xuefu Load, Honggutan District, Nanchang, 330031, China.
[Ti] Título:Inhibition of NAMPT aggravates high fat diet-induced hepatic steatosis in mice through regulating Sirt1/AMPKα/SREBP1 signaling pathway.
[So] Source:Lipids Health Dis;16(1):82, 2017 Apr 27.
[Is] ISSN:1476-511X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Nonalcoholic fatty liver disease is one of the most common liver diseases in the world and is a typical hepatic manifestation of metabolic syndrome which is characterized with lipid accumulation in liver. Nicotinamide phosphoribosyltransferase (NAMPT) has been recently identified as an enzyme involved in nicotinamide adenine dinucleotide (NAD ) biosynthesis and plays an important role in cellular metabolism in variety of organs in mammals. The aim of this study was to investigate the effects of NAMPT on high fat diet-induced hepatic steatosis. METHODS: Hepatic steatosis model was induced by high fat diet (HFD) in C57BL/6 mice in vivo. HepG2 and Hep1-6 hepatocytes were transfected with NAMPT vector plasmid or treated with NAMPT inhibitor FK866 and then incubated with oleic acid. Lipids accumulation was examined by HE staining or oil red staining. Quantitative RT-PCR and Western blot were used to measure expressions of the genes involved in lipogenic synthesis. RESULTS: FK866 significantly promoted liver steatosis in the mice fed with HFD and hepatic lipid accumulation in vitro, accompanied by the increases of the expressions of lipogenic genes such as sterol regulatory element-binding protein 1 (SREBP1) and fatty acid synthase (FASN). Nicotinamide mononucleotide (NMN) and NAD significantly rescued the actions of FK866 in vitro. In contrast, overexpression of NAMPT in HepG2 and Hep1-6 hepatocytes ameliorated hepatic lipid accumulation. In addition, FK866 decreased the protein levels of Sirt1 and phospho-AMPKα in liver of the HFD fed mice. Furthermore, Resveratrol, a Sirt1 activator, significantly reduced lipogenic gene expressions, while EX-527, a Sirt1 specific inhibitor, had the opposite effects. CONCLUSION: Our results demonstrated that inhibition of NAMPT aggravated the HFD- or oleic acid-induced hepatic steatosis through suppressing Sirt1-mediated signaling pathway. On the one hand, the inhibition of NAMPT reduced the production of NAD through inhibiting the NAD salvage pathway, resulting in the decrease of Sirt1 activity, and then attenuated the deacetylation of SREBP1 in which the inhibition of SREBP1 activity promoted the expressions of FASN and ACC. On the other hand, the reduced Sirt1 activity alleviated the activation of AMPKα to further enhance SREBP1 activities.
[Mh] Termos MeSH primário: Proteínas Quinases Ativadas por AMP/genética
Citocinas/genética
Fígado/enzimologia
Nicotinamida Fosforribosiltransferase/genética
Hepatopatia Gordurosa não Alcoólica/genética
Sirtuína 1/genética
Proteína de Ligação a Elemento Regulador de Esterol 1/genética
[Mh] Termos MeSH secundário: Proteínas Quinases Ativadas por AMP/metabolismo
Acrilamidas/farmacologia
Animais
Carbazóis/farmacologia
Linhagem Celular
Citocinas/antagonistas & inibidores
Citocinas/metabolismo
Dieta Hiperlipídica/efeitos adversos
Inibidores Enzimáticos/farmacologia
Regulação da Expressão Gênica
Células Hep G2
Hepatócitos/efeitos dos fármacos
Hepatócitos/enzimologia
Hepatócitos/patologia
Seres Humanos
Fígado/efeitos dos fármacos
Fígado/patologia
Masculino
Camundongos
Camundongos Endogâmicos C57BL
NAD/farmacologia
Mononucleotídeo de Nicotinamida/farmacologia
Nicotinamida Fosforribosiltransferase/antagonistas & inibidores
Nicotinamida Fosforribosiltransferase/metabolismo
Hepatopatia Gordurosa não Alcoólica/enzimologia
Hepatopatia Gordurosa não Alcoólica/etiologia
Hepatopatia Gordurosa não Alcoólica/patologia
Ácido Oleico/farmacologia
Piperidinas/farmacologia
Transdução de Sinais
Sirtuína 1/antagonistas & inibidores
Sirtuína 1/metabolismo
Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
Estilbenos/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide); 0 (Acrylamides); 0 (Carbazoles); 0 (Cytokines); 0 (Enzyme Inhibitors); 0 (N-(4-(1-benzoylpiperidin-4-yl)butyl)-3-(pyridin-3-yl)acrylamide); 0 (Piperidines); 0 (Srebf1 protein, mouse); 0 (Sterol Regulatory Element Binding Protein 1); 0 (Stilbenes); 0U46U6E8UK (NAD); 1094-61-7 (Nicotinamide Mononucleotide); 2UMI9U37CP (Oleic Acid); EC 2.4.2.12 (Nicotinamide Phosphoribosyltransferase); EC 2.4.2.12 (nicotinamide phosphoribosyltransferase, mouse); EC 2.7.11.1 (AMPK alpha1 subunit, mouse); EC 2.7.11.31 (AMP-Activated Protein Kinases); EC 3.5.1.- (Sirt1 protein, mouse); EC 3.5.1.- (Sirtuin 1); Q369O8926L (resveratrol)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180219
[Lr] Data última revisão:
180219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1186/s12944-017-0464-z


  4 / 25237 MEDLINE  
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[PMID]:28745425
[Au] Autor:Filipov Y; Domanskyi S; Wood ML; Gamella M; Privman V; Katz E
[Ad] Endereço:Department of Chemistry and Biomolecular Science, Clarkson University, Potsdam, NY, 13699, USA.
[Ti] Título:Experimental Realization of a High-Quality Biochemical XOR Gate.
[So] Source:Chemphyschem;18(20):2908-2915, 2017 Oct 19.
[Is] ISSN:1439-7641
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:We report an experimental realization of a biochemical XOR gate function that avoids many of the pitfalls of earlier realizations based on biocatalytic cascades. Inputs-represented by pairs of chemicals-cross-react to largely cancel out when both are nearly equal. The cross-reaction can be designed to also optimize gate functioning for noise handling. When not equal, the residual inputs are further processed to result in the output of the XOR type, by biocatalytic steps that allow for further gate-function optimization. The quality of the realized XOR gate is theoretically analyzed.
[Mh] Termos MeSH primário: Álcool Desidrogenase/metabolismo
Oxirredutases do Álcool/metabolismo
Biocatálise
Glucose Oxidase/metabolismo
Hexoquinase/metabolismo
NAD/metabolismo
Peroxidase/metabolismo
[Mh] Termos MeSH secundário: Armoracia/enzimologia
Aspergillus niger/enzimologia
Modelos Moleculares
Pichia/enzimologia
Saccharomyces cerevisiae/enzimologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0U46U6E8UK (NAD); EC 1.1.- (Alcohol Oxidoreductases); EC 1.1.1.1 (Alcohol Dehydrogenase); EC 1.1.3.13 (alcohol oxidase); EC 1.1.3.4 (Glucose Oxidase); EC 1.11.1.7 (Peroxidase); EC 2.7.1.1 (Hexokinase)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170727
[St] Status:MEDLINE
[do] DOI:10.1002/cphc.201700705


  5 / 25237 MEDLINE  
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[PMID]:28473297
[Au] Autor:Pochapsky TC; Wong N; Zhuang Y; Futcher J; Pandelia ME; Teitz DR; Colthart AM
[Ad] Endereço:Department of Chemistry, Brandeis University, 415 South St., Waltham, MA 02454-9110, USA. Electronic address: pochapsk@brandeis.edu.
[Ti] Título:NADH reduction of nitroaromatics as a probe for residual ferric form high-spin in a cytochrome P450.
[So] Source:Biochim Biophys Acta;1866(1):126-133, 2018 01.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The existence of a substrate-sensitive equilibrium between high spin (S=5/2) and low spin (S=1/2) ferric iron is a well-established phenomenon in the cytochrome P450 (CYP) superfamily, although its origins are still a subject of discussion. A series of mutations that strongly perturb the spin state equilibrium in the camphor hydroxylase CYP101A1 were recently described (Colthart et al., Sci. Rep. 6, 22035 (2016)). Wild type CYP101A1 as well as some CYP101A1 mutants are herein shown to be capable of catalyzing the reduction of nitroacetophenones by NADH to the corresponding anilino compounds (nitroreductase or NRase activity). The distinguishing characteristic between those mutants that catalyze the reduction and those that cannot appears to be the extent to which residual high spin form exists in the absence of the native substrate d-camphor, with those showing the largest spin state shifts upon camphor binding also exhibiting NRase activity. Optical and EPR spectroscopy was used to further examine these phenomena. These results suggest that reduction of nitroaromatics may provide a useful probe of residual high spin states in the CYP superfamily. This article is part of a Special Issue entitled: Cytochrome P450 biodiversity and biotechnology, edited by Erika Plettner, Gianfranco Gilardi, Luet Wong, Vlada Urlacher, Jared Goldstone.
[Mh] Termos MeSH primário: Acetofenonas/química
Proteínas de Bactérias/química
Cânfora 5-Mono-Oxigenase/química
Cânfora/química
Compostos Férricos/química
Heme/química
NAD/química
[Mh] Termos MeSH secundário: Acetofenonas/metabolismo
Motivos de Aminoácidos
Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Sítios de Ligação
Biocatálise
Cânfora/metabolismo
Cânfora 5-Mono-Oxigenase/genética
Cânfora 5-Mono-Oxigenase/metabolismo
Clonagem Molecular
Espectroscopia de Ressonância de Spin Eletrônica
Escherichia coli/genética
Escherichia coli/metabolismo
Expressão Gênica
Heme/metabolismo
Cinética
Modelos Moleculares
NAD/metabolismo
Oxirredução
Ligação Proteica
Conformação Proteica em alfa-Hélice
Conformação Proteica em Folha beta
Domínios e Motivos de Interação entre Proteínas
Proteínas Recombinantes/química
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Acetophenones); 0 (Bacterial Proteins); 0 (Ferric Compounds); 0 (Recombinant Proteins); 0U46U6E8UK (NAD); 100-19-6 (4-nitroacetophenone); 42VZT0U6YR (Heme); 76-22-2 (Camphor); EC 1.14.15.1 (Camphor 5-Monooxygenase)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180208
[Lr] Data última revisão:
180208
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170506
[St] Status:MEDLINE


  6 / 25237 MEDLINE  
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[PMID]:29227076
[Au] Autor:Danylovych HV
[Ti] Título:Evaluation of functioning of mitochondrial electron transport chain with NADH and FAD autofluorescence
[So] Source:Ukr Biochem J;88(1):31-43, 2016 Jan-Feb.
[Is] ISSN:2409-4943
[Cp] País de publicação:Ukraine
[La] Idioma:eng
[Ab] Resumo:We prove the feasibility of evaluation of mitochondrial electron transport chain function in isolated mitochondria of smooth muscle cells of rats from uterus using fluorescence of NADH and FAD coenzymes. We found the inversely directed changes in FAD and NADH fluorescence intensity under normal functioning of mitochondrial electron transport chain. The targeted effect of inhibitors of complex I, III and IV changed fluorescence of adenine nucleotides. Rotenone (5 µM) induced rapid increase in NADH fluorescence due to inhibition of complex I, without changing in dynamics of FAD fluorescence increase. Antimycin A, a complex III inhibitor, in concentration of 1 µg/ml caused sharp increase in NADH fluorescence and moderate increase in FAD fluorescence in comparison to control. NaN3 (5 mM), a complex IV inhibitor, and CCCP (10 µM), a protonophore, caused decrease in NADH and FAD fluorescence. Moreover, all the inhibitors caused mitochondria swelling. NO donors, e.g. 0.1 mM sodium nitroprusside and sodium nitrite similarly to the effects of sodium azide. Energy-dependent Ca2+ accumulation in mitochondrial matrix (in presence of oxidation substrates and Mg-ATP2- complex) is associated with pronounced drop in NADH and FAD fluorescence followed by increased fluorescence of adenine nucleotides, which may be primarily due to Ca2+- dependent activation of dehydrogenases of citric acid cycle. Therefore, the fluorescent signal of FAD and NADH indicates changes in oxidation state of these nucleotides in isolated mitochondria, which may be used to assay the potential of effectors of electron transport chain.
[Mh] Termos MeSH primário: Complexo III da Cadeia de Transporte de Elétrons/metabolismo
Complexo IV da Cadeia de Transporte de Elétrons/metabolismo
Complexo I de Transporte de Elétrons/metabolismo
Flavina-Adenina Dinucleotídeo/química
Mitocôndrias/metabolismo
NAD/química
[Mh] Termos MeSH secundário: Animais
Antimicina A/farmacologia
Cálcio/metabolismo
Carbonil Cianeto m-Clorofenil Hidrazona/farmacologia
Fracionamento Celular
Transporte de Elétrons/efeitos dos fármacos
Complexo I de Transporte de Elétrons/antagonistas & inibidores
Complexo III da Cadeia de Transporte de Elétrons/antagonistas & inibidores
Complexo IV da Cadeia de Transporte de Elétrons/antagonistas & inibidores
Inibidores Enzimáticos/farmacologia
Feminino
Flavina-Adenina Dinucleotídeo/metabolismo
Mitocôndrias/efeitos dos fármacos
Miócitos de Músculo Liso/efeitos dos fármacos
Miócitos de Músculo Liso/metabolismo
Miométrio/efeitos dos fármacos
Miométrio/metabolismo
NAD/metabolismo
Nitroprussiato/farmacologia
Imagem Óptica
Ratos
Rotenona/farmacologia
Azida Sódica/farmacologia
Nitrito de Sódio/farmacologia
Desacopladores/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (Uncoupling Agents); 03L9OT429T (Rotenone); 0U46U6E8UK (NAD); 146-14-5 (Flavin-Adenine Dinucleotide); 169D1260KM (Nitroprusside); 555-60-2 (Carbonyl Cyanide m-Chlorophenyl Hydrazone); 642-15-9 (Antimycin A); 968JJ8C9DV (Sodium Azide); EC 1.10.2.2 (Electron Transport Complex III); EC 1.6.5.3 (Electron Transport Complex I); EC 1.9.3.1 (Electron Transport Complex IV); M0KG633D4F (Sodium Nitrite); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180116
[Lr] Data última revisão:
180116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171212
[St] Status:MEDLINE
[do] DOI:10.15407/ubj88.01.031


  7 / 25237 MEDLINE  
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[PMID]:29211728
[Au] Autor:Airhart SE; Shireman LM; Risler LJ; Anderson GD; Nagana Gowda GA; Raftery D; Tian R; Shen DD; O'Brien KD
[Ad] Endereço:Division of Cardiology, Department of Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America.
[Ti] Título:An open-label, non-randomized study of the pharmacokinetics of the nutritional supplement nicotinamide riboside (NR) and its effects on blood NAD+ levels in healthy volunteers.
[So] Source:PLoS One;12(12):e0186459, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: The co-primary objectives of this study were to determine the human pharmacokinetics (PK) of oral NR and the effect of NR on whole blood nicotinamide adenine dinucleotide (NAD+) levels. BACKGROUND: Though mitochondrial dysfunction plays a critical role in the development and progression of heart failure, no mitochondria-targeted therapies have been translated into clinical practice. Recent murine studies have reported associations between imbalances in the NADH/NAD+ ratio with mitochondrial dysfunction in multiple tissues, including myocardium. Moreover, an NAD+ precursor, nicotinamide mononucleotide, improved cardiac function, while another NAD+ precursor, nicotinamide riboside (NR), improved mitochondrial function in muscle, liver and brown adipose. Thus, PK studies of NR in humans is critical for future clinical trials. METHODS: In this non-randomized, open-label PK study of 8 healthy volunteers, 250 mg NR was orally administered on Days 1 and 2, then uptitrated to peak dose of 1000 mg twice daily on Days 7 and 8. On the morning of Day 9, subjects completed a 24-hour PK study after receiving 1000 mg NR at t = 0. Whole-blood levels of NR, clinical blood chemistry, and NAD+ levels were analyzed. RESULTS: Oral NR was well tolerated with no adverse events. Significant increases comparing baseline to mean concentrations at steady state (Cave,ss) were observed for both NR (p = 0.03) and NAD+ (p = 0.001); the latter increased by 100%. Absolute changes from baseline to Day 9 in NR and NAD+ levels correlated highly (R2 = 0.72, p = 0.008). CONCLUSIONS: Because NR increases circulating NAD+ in humans, NR may have potential as a therapy in patients with mitochondrial dysfunction due to genetic and/or acquired diseases.
[Mh] Termos MeSH primário: Suplementos Nutricionais
Voluntários Saudáveis
NAD/sangue
Niacinamida/análogos & derivados
[Mh] Termos MeSH secundário: Administração Oral
Adulto
Feminino
Seres Humanos
Recém-Nascido
Masculino
Meia-Idade
Niacinamida/administração & dosagem
Niacinamida/efeitos adversos
Niacinamida/sangue
Niacinamida/farmacocinética
Adulto Jovem
[Pt] Tipo de publicação:CLINICAL TRIAL; JOURNAL ARTICLE
[Nm] Nome de substância:
0I8H2M0L7N (nicotinamide-beta-riboside); 0U46U6E8UK (NAD); 25X51I8RD4 (Niacinamide)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180110
[Lr] Data última revisão:
180110
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171207
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0186459


  8 / 25237 MEDLINE  
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[PMID]:29253849
[Au] Autor:Gallego-Jara J; Écija Conesa A; de Diego Puente T; Lozano Terol G; Cánovas Díaz M
[Ad] Endereço:Department of Biochemistry and Molecular Biology and Immunology (B), Faculty of Chemistry, University of Murcia, Campus of Espinardo, Regional Campus of International Excellence ''Campus Mare Nostrum", Murcia, Spain.
[Ti] Título:Characterization of CobB kinetics and inhibition by nicotinamide.
[So] Source:PLoS One;12(12):e0189689, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Lysine acetylation has emerged as a global protein regulation system in all domains of life. Sirtuins, or Sir2-like enzymes, are a family of histone deacetylases characterized by their employing NAD+ as a co-substrate. Sirtuins can deacetylate several acetylated proteins, but a consensus substrate recognition sequence has not yet been established. Product inhibition of many eukaryotic sirtuins by nicotinamide and its analogues has been studied in vitro due to their potential role as anticancer agents. In this work, the kinetics of CobB, the main Escherichia coli deacetylase, have been characterized. To our knowledge, this is the first kinetic characterization of a sirtuin employing a fully acetylated and natively folded protein as a substrate. CobB deacetylated several acetyl-CoA synthetase acetylated lysines with a single kinetic rate. In addition, in vitro nicotinamide inhibition of CobB has been characterized, and the intracellular nicotinamide concentrations have been determined under different growth conditions. The results suggest that nicotinamide can act as a CobB regulator in vivo. A nicotinamidase deletion strain was thus phenotypically characterized, and it behaved similarly to the ΔcobB strain. The results of this work demonstrate the potential regulatory role of the nicotinamide metabolite in vivo.
[Mh] Termos MeSH primário: Proteínas de Escherichia coli/antagonistas & inibidores
Proteínas de Escherichia coli/química
Escherichia coli/enzimologia
Niacinamida/química
Sirtuínas/antagonistas & inibidores
Sirtuínas/química
[Mh] Termos MeSH secundário: Acetatos/química
Acetilcoenzima A/metabolismo
Acetilação
Deleção de Genes
Histonas/metabolismo
Cinética
Lisina/química
NAD/metabolismo
Fenótipo
Plasmídeos/metabolismo
Dobramento de Proteína
Sirtuínas/metabolismo
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acetates); 0 (Escherichia coli Proteins); 0 (Histones); 0U46U6E8UK (NAD); 25X51I8RD4 (Niacinamide); 72-89-9 (Acetyl Coenzyme A); EC 3.5.1.- (Sirtuins); EC 3.5.1.- (cobB protein, E Coli); K3Z4F929H6 (Lysine)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180108
[Lr] Data última revisão:
180108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171219
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189689


  9 / 25237 MEDLINE  
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[PMID]:28450391
[Au] Autor:Korge P; Calmettes G; John SA; Weiss JN
[Ad] Endereço:From the UCLA Cardiovascular Research Laboratory and the Departments of Medicine (Cardiology) and Physiology, David Geffen School of Medicine at UCLA, Los Angeles, California 90095.
[Ti] Título:Reactive oxygen species production induced by pore opening in cardiac mitochondria: The role of complex III.
[So] Source:J Biol Chem;292(24):9882-9895, 2017 06 16.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Recent evidence has implicated succinate-driven reverse electron transport (RET) through complex I as a major source of damaging reactive oxygen species (ROS) underlying reperfusion injury after prolonged cardiac ischemia. However, this explanation may be incomplete, because RET on reperfusion is self-limiting and therefore transient. RET can only generate ROS when mitochondria are well polarized, and it ceases when permeability transition pores (PTP) open during reperfusion. Because prolonged ischemia/reperfusion also damages electron transport complexes, we investigated whether such damage could lead to ROS production after PTP opening has occurred. Using isolated cardiac mitochondria, we demonstrate a novel mechanism by which antimycin-inhibited complex III generates significant amounts of ROS in the presence of Mg and NAD and the absence of exogenous substrates upon inner membrane pore formation by alamethicin or Ca -induced PTP opening. We show that H O production under these conditions is related to Mg -dependent NADH generation by malic enzyme. H O production is blocked by stigmatellin, indicating its origin from complex III, and by piericidin, demonstrating the importance of NADH-related ubiquinone reduction for ROS production under these conditions. For maximal ROS production, the rate of NADH generation has to be equal or below that of NADH oxidation, as further increases in [NADH] elevate ubiquinol-related complex III reduction beyond the optimal range for ROS generation. These results suggest that if complex III is damaged during ischemia, PTP opening may result in succinate/malate-fueled ROS production from complex III due to activation of malic enzyme by increases in matrix [Mg ], [NAD ], and [ADP].
[Mh] Termos MeSH primário: Complexo III da Cadeia de Transporte de Elétrons/metabolismo
Malato Desidrogenase/metabolismo
Mitocôndrias Cardíacas/metabolismo
Espécies Reativas de Oxigênio/agonistas
[Mh] Termos MeSH secundário: Difosfato de Adenosina/metabolismo
Alameticina/farmacologia
Animais
Antimicina A/análogos & derivados
Antimicina A/farmacologia
Biocatálise/efeitos dos fármacos
Sinalização do Cálcio/efeitos dos fármacos
Complexo III da Cadeia de Transporte de Elétrons/antagonistas & inibidores
Ativação Enzimática/efeitos dos fármacos
Inibidores Enzimáticos/farmacologia
Peróxido de Hidrogênio/metabolismo
Ionóforos/farmacologia
Magnésio/metabolismo
Malato Desidrogenase/química
Mitocôndrias Cardíacas/química
Mitocôndrias Cardíacas/efeitos dos fármacos
NAD/metabolismo
Oxirredução
Polienos/farmacologia
Porosidade/efeitos dos fármacos
Piridinas/farmacologia
Coelhos
Espécies Reativas de Oxigênio/metabolismo
Ubiquinona/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (Ionophores); 0 (Polyenes); 0 (Pyridines); 0 (Reactive Oxygen Species); 0U46U6E8UK (NAD); 11118-72-2 (antimycin); 1339-63-5 (Ubiquinone); 27061-78-5 (Alamethicin); 61D2G4IYVH (Adenosine Diphosphate); 642-15-9 (Antimycin A); 8VT513UJ9R (piericidin A); 91682-96-1 (stigmatellin); BBX060AN9V (Hydrogen Peroxide); EC 1.1.1.37 (Malate Dehydrogenase); EC 1.10.2.2 (Electron Transport Complex III); I38ZP9992A (Magnesium)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171228
[Lr] Data última revisão:
171228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M116.768317


  10 / 25237 MEDLINE  
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[PMID]:29207896
[Au] Autor:Chaker M; Minden A; Chen S; Weiss RH; Chini EN; Mahipal A; Azmi AS
[Ad] Endereço:a Department of Oncology , Wayne State University School of Medicine, Karmanos Cancer Institute , Detroit , MI , USA.
[Ti] Título:Rho GTPase effectors and NAD metabolism in cancer immune suppression.
[So] Source:Expert Opin Ther Targets;22(1):9-17, 2018 Jan.
[Is] ISSN:1744-7631
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Sustained proliferative signaling and de-regulated cellular bioenergetics are two of the chief hallmarks of cancer. Alterations in the Ras pathway and its downstream effectors are among the major drivers for uncontrolled cell growth in many cancers. The GTPases are one of the signaling molecules that activate crucial signal transducing pathways downstream of Ras through several effector proteins. The GTPases (GTP bound) interact with several effectors and modulate a number of different biological pathways including those that regulate cytoskeleton, cellular motility, cytokinesis, proliferation, apoptosis, transcription and nuclear signaling. Similarly, the altered glycolytic pathway, the so-called 'Warburg effect', rewires tumor cell metabolism to support the biosynthetic requirements of uncontrolled proliferation. There exists strong evidence for the critical role of the glycolytic pathway's rate limiting enzymes in promoting immunosuppression. Areas covered: We review the emerging roles of GTPase effector proteins particularly the p21 activated kinase 4 (PAK4) and nicotinamide biosynthetic pathway enzyme nicotinamide phosphoribosyltransferase (NAMPT) as signaling molecules in immune surveillance and the immune response. Expert opinion: In this expert opinion article we highlight the recent information on the role of GTPases and the metabolic enzymes on the immune microenvironment and propose some unique immune therapeutic opportunities.
[Mh] Termos MeSH primário: NAD/metabolismo
Neoplasias/imunologia
Proteínas rho de Ligação ao GTP/metabolismo
[Mh] Termos MeSH secundário: Animais
Seres Humanos
Imunoterapia/métodos
NAD/imunologia
Neoplasias/terapia
Transdução de Sinais/imunologia
Microambiente Tumoral/imunologia
Proteínas rho de Ligação ao GTP/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0U46U6E8UK (NAD); EC 3.6.5.2 (rho GTP-Binding Proteins)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171227
[Lr] Data última revisão:
171227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171207
[St] Status:MEDLINE
[do] DOI:10.1080/14728222.2018.1413091



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