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  1 / 148 MEDLINE  
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[PMID]:28060932
[Au] Autor:Ortiz ME; Bleckwedel J; Fadda S; Picariello G; Hebert EM; Raya RR; Mozzi F
[Ad] Endereço:Centro de Referencia para Lactobacilos (CERELA)-CONICET, Chacabuco 145, San Miguel de Tucumán, Tucumán, Argentina.
[Ti] Título:Global Analysis of Mannitol 2-Dehydrogenase in Lactobacillus reuteri CRL 1101 during Mannitol Production through Enzymatic, Genetic and Proteomic Approaches.
[So] Source:PLoS One;12(1):e0169441, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Several plants, fungi, algae, and certain bacteria produce mannitol, a polyol derived from fructose. Mannitol has multiple industrial applications in the food, pharmaceutical, and medical industries, being mainly used as a non-metabolizable sweetener in foods. Many heterofermentative lactic acid bacteria synthesize mannitol when an alternative electron acceptor such as fructose is present in the medium. In previous work, we reported the ability of Lactobacillus reuteri CRL 1101 to efficiently produce mannitol from sugarcane molasses as carbon source at constant pH of 5.0; the activity of the enzyme mannitol 2-dehydrogenase (MDH) responsible for the fructose conversion into mannitol being highest during the log cell growth phase. Here, a detailed assessment of the MDH activity and relative expression of the mdh gene during the growth of L. reuteri CRL 1101 in the presence of fructose is presented. It was observed that MDH was markedly induced by the presence of fructose. A direct correlation between the maximum MDH enzyme activity and a high level of mdh transcript expression during the log-phase of cells grown in a fructose-containing chemically defined medium was detected. Furthermore, two proteomic approaches (2DE and shotgun proteomics) applied in this study confirmed the inducible expression of MDH in L. reuteri. A global study of the effect of fructose on activity, mdh gene, and protein expressions of MDH in L. reuteri is thus for the first time presented. This work represents a deep insight into the polyol formation by a Lactobacillus strain with biotechnological potential in the nutraceutics and pharmaceutical areas.
[Mh] Termos MeSH primário: Genômica
Lactobacillus reuteri/genética
Lactobacillus reuteri/metabolismo
Manitol Desidrogenases/metabolismo
Manitol/metabolismo
Proteômica
[Mh] Termos MeSH secundário: Metabolismo dos Carboidratos
Carboidratos/química
Ativação Enzimática
Frutose/metabolismo
Genômica/métodos
Proteômica/métodos
Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carbohydrates); 30237-26-4 (Fructose); 3OWL53L36A (Mannitol); EC 1.1.- (Mannitol Dehydrogenases)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170815
[Lr] Data última revisão:
170815
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170107
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0169441


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[PMID]:27338577
[Au] Autor:Zahid N; Deppenmeier U
[Ad] Endereço:Institute of Microbiology and Biotechnology, Meckenheimer Allee 168, 53115, Bonn, Germany.
[Ti] Título:Role of mannitol dehydrogenases in osmoprotection of Gluconobacter oxydans.
[So] Source:Appl Microbiol Biotechnol;100(23):9967-9978, 2016 Dec.
[Is] ISSN:1432-0614
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Gluconobacter (G.) oxydans is able to incompletely oxidize various sugars and polyols for the production of biotechnologically important compound. Recently, we have shown that the organism produces and accumulates mannitol as compatible solute under osmotic stress conditions. The present study describes the role of two cytoplasmic mannitol dehydrogenases for osmotolerance of G. oxydans. It was shown that Gox1432 is a NADP -dependent mannitol dehydrogenase (EC 1.1.1.138), while Gox0849 uses NAD as cofactor (EC 1.1.1.67). The corresponding genes were deleted and the mutants were analyzed for growth under osmotic stress and non-stress conditions. A severe growth defect was detected for Δgox1432 when grown in high osmotic media, while the deletion of gox0849 had no effect when cells were exposed to 450 mM sucrose in the medium. Furthermore, the intracellular mannitol content was reduced in the mutant lacking the NADP -dependent enzyme Gox1432 in comparison to the parental strain and the Δgox0849 mutant under stress conditions. In addition, transcriptional analysis revealed that Gox1432 is more important for mannitol production in G. oxydans than Gox0849 as the transcript abundance of gene gox1432 was 30-fold higher than of gox0849. In accordance, the activity of the NADH-dependent enzyme Gox0849 in the cell cytoplasm was 10-fold lower in comparison to the NADPH-dependent mannitol dehydrogenase Gox1432. Overexpression of gox1432 in the corresponding deletion mutant restored growth of the cells under osmotic stress, further strengthening the importance of the NADP -dependent mannitol dehydrogenase for osmotolerance in G. oxydans. These findings provide detailed insights into the molecular mechanism of mannitol-mediated osmoprotection in G. oxydans and are helpful engineering strains with improved osmotolerance for biotechnological applications.
[Mh] Termos MeSH primário: Gluconobacter oxydans/enzimologia
Gluconobacter oxydans/metabolismo
Manitol Desidrogenases/metabolismo
Manitol/metabolismo
Osmorregulação
[Mh] Termos MeSH secundário: Meios de Cultura/química
Deleção de Genes
Perfilação da Expressão Gênica
Teste de Complementação Genética
Gluconobacter oxydans/genética
Gluconobacter oxydans/crescimento & desenvolvimento
Manitol Desidrogenases/genética
Pressão Osmótica
Estresse Fisiológico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Culture Media); 3OWL53L36A (Mannitol); EC 1.1.- (Mannitol Dehydrogenases)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170124
[Lr] Data última revisão:
170124
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160625
[St] Status:MEDLINE


  3 / 148 MEDLINE  
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[PMID]:26084891
[Au] Autor:Ortiz ME; Raya RR; Mozzi F
[Ad] Endereço:Departamento de Tecnología y Desarrollo, Centro de Referencia para Lactobacilos (CERELA)-CONICET, Chacabuco 145, 4000, San Miguel de Tucumán, Argentina.
[Ti] Título:Efficient mannitol production by wild-type Lactobacillus reuteri CRL 1101 is attained at constant pH using a simplified culture medium.
[So] Source:Appl Microbiol Biotechnol;99(20):8717-29, 2015 Oct.
[Is] ISSN:1432-0614
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Mannitol is a natural polyol with multiple industrial applications. In this work, mannitol production by Lactobacillus reuteri CRL 1101 was studied at free- and controlled-pH (6.0-4.8) fermentations using a simplified culture medium containing yeast and beef extracts and sugarcane molasses. The activity of mannitol 2-dehydrogenase (MDH), the enzyme responsible for mannitol synthesis, was determined. The effect of the initial biomass concentration was further studied. Mannitol production (41.5 ± 1.1 g/l), volumetric productivity (Q Mtl 1.73 ± 0.05 g/l h), and yield (Y Mtl 105 ± 11 %) were maximum at pH 5.0 after 24 h while the highest MDH activity (1.66 ± 0.09 U/mg protein) was obtained at pH 6.0. No correlation between mannitol production and MDH activity was observed when varying the culture pH. The increase (up to 2000-fold) in the initial biomass concentration did not improve mannitol formation after 24 h although a 2-fold higher amount was produced at 8 h using 1 or 2 g cell dry weight/l comparing to the control (0.001 g cell dry weight/l). Finally, mannitol isolation under optimum fermentation conditions was achieved. The mannitol production obtained in this study is the highest reported so far by a wild-type L. reuteri strain and, more interestingly, using a simplified culture medium.
[Mh] Termos MeSH primário: Meios de Cultura/química
Lactobacillus reuteri/metabolismo
Manitol/metabolismo
[Mh] Termos MeSH secundário: Fermentação
Concentração de Íons de Hidrogênio
Manitol Desidrogenases/análise
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Culture Media); 3OWL53L36A (Mannitol); EC 1.1.- (Mannitol Dehydrogenases)
[Em] Mês de entrada:1606
[Cu] Atualização por classe:150916
[Lr] Data última revisão:
150916
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150619
[St] Status:MEDLINE
[do] DOI:10.1007/s00253-015-6730-y


  4 / 148 MEDLINE  
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[PMID]:25959598
[Au] Autor:Dulermo T; Lazar Z; Dulermo R; Rakicka M; Haddouche R; Nicaud JM
[Ad] Endereço:INRA, UMR1319 Micalis, F-78350 Jouy-en-Josas, France; AgroParisTech, UMR Micalis, Jouy-en-Josas, France.
[Ti] Título:Analysis of ATP-citrate lyase and malic enzyme mutants of Yarrowia lipolytica points out the importance of mannitol metabolism in fatty acid synthesis.
[So] Source:Biochim Biophys Acta;1851(9):1107-17, 2015 Sep.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The role of the two key enzymes of fatty acid (FA) synthesis, ATP-citrate lyase (Acl) and malic enzyme (Mae), was analyzed in the oleaginous yeast Yarrowia lipolytica. In most oleaginous yeasts, Acl and Mae are proposed to provide, respectively, acetyl-CoA and NADPH for FA synthesis. Acl was mainly studied at the biochemical level but no strain depleted for this enzyme was analyzed in oleaginous microorganisms. On the other hand the role of Mae in FA synthesis in Y. lipolytica remains unclear since it was proposed to be a mitochondrial NAD(H)-dependent enzyme and not a cytosolic NADP(H)-dependent enzyme. In this study, we analyzed for the first time strains inactivated for corresponding genes. Inactivation of ACL1 decreases FA synthesis by 60 to 80%, confirming its essential role in FA synthesis in Y. lipolytica. Conversely, inactivation of MAE1 has no effects on FA synthesis, except in a FA overaccumulating strain where it improves FA synthesis by 35%. This result definitively excludes Mae as a major key enzyme for FA synthesis in Y. lipolytica. During the analysis of both mutants, we observed a negative correlation between FA and mannitol level. As mannitol and FA pathways may compete for carbon storage, we inactivated YlSDR, encoding a mannitol dehydrogenase converting fructose and NADPH into mannitol and NADP+. The FA content of the resulting mutant was improved by 60% during growth on fructose, demonstrating that mannitol metabolism may modulate FA synthesis in Y. lipolytica.
[Mh] Termos MeSH primário: ATP Citrato (pro-S)-Liase/metabolismo
Ácidos Graxos/metabolismo
Proteínas Fúngicas/metabolismo
Deleção de Genes
Regulação Fúngica da Expressão Gênica
Malato Desidrogenase/metabolismo
Yarrowia/metabolismo
[Mh] Termos MeSH secundário: ATP Citrato (pro-S)-Liase/deficiência
ATP Citrato (pro-S)-Liase/genética
Acetilcoenzima A/metabolismo
Frutose/metabolismo
Proteínas Fúngicas/genética
Metabolismo dos Lipídeos/genética
Malato Desidrogenase/deficiência
Malato Desidrogenase/genética
Manitol/metabolismo
Manitol Desidrogenases/deficiência
Manitol Desidrogenases/genética
Manitol Desidrogenases/metabolismo
NADP/metabolismo
Plasmídeos/química
Plasmídeos/metabolismo
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Transdução de Sinais
Yarrowia/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Fatty Acids); 0 (Fungal Proteins); 0 (Recombinant Proteins); 30237-26-4 (Fructose); 3OWL53L36A (Mannitol); 53-59-8 (NADP); 72-89-9 (Acetyl Coenzyme A); EC 1.1.- (Mannitol Dehydrogenases); EC 1.1.1.37 (Malate Dehydrogenase); EC 1.1.1.39 (malate dehydrogenase (decarboxylating)); EC 2.3.3.8 (ATP Citrate (pro-S)-Lyase)
[Em] Mês de entrada:1510
[Cu] Atualização por classe:161126
[Lr] Data última revisão:
161126
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150512
[St] Status:MEDLINE


  5 / 148 MEDLINE  
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[PMID]:25752240
[Au] Autor:Lucas JE; Siegel JB
[Ad] Endereço:Genome Center, University of California, Davis, California, 95616.
[Ti] Título:Quantitative functional characterization of conserved molecular interactions in the active site of mannitol 2-dehydrogenase.
[So] Source:Protein Sci;24(6):936-45, 2015 Jun.
[Is] ISSN:1469-896X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Enzyme active site residues are often highly conserved, indicating a significant role in function. In this study we quantitate the functional contribution for all conserved molecular interactions occurring within a Michaelis complex for mannitol 2-dehydrogenase derived from Pseudomonas fluorescens (pfMDH). Through systematic mutagenesis of active site residues, we reveal that the molecular interactions in pfMDH mediated by highly conserved residues not directly involved in reaction chemistry can be as important to catalysis as those directly involved in the reaction chemistry. This quantitative analysis of the molecular interactions within the pfMDH active site provides direct insight into the functional role of each molecular interaction, several of which were unexpected based on canonical sequence conservation and structural analyses.
[Mh] Termos MeSH primário: Domínio Catalítico/genética
Manitol Desidrogenases/química
Manitol Desidrogenases/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Proteínas de Bactérias/química
Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Catálise
Domínio Catalítico/fisiologia
Sequência Conservada
Manitol Desidrogenases/genética
Mutagênese Sítio-Dirigida
Pseudomonas fluorescens/enzimologia
Pseudomonas fluorescens/genética
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Bacterial Proteins); EC 1.1.- (Mannitol Dehydrogenases)
[Em] Mês de entrada:1602
[Cu] Atualização por classe:160601
[Lr] Data última revisão:
160601
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150311
[St] Status:MEDLINE
[do] DOI:10.1002/pro.2669


  6 / 148 MEDLINE  
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[PMID]:25548051
[Au] Autor:Groisillier A; Labourel A; Michel G; Tonon T
[Ad] Endereço:Sorbonne Universités, UPMC Université Paris 06, UMR 8227, Integrative Biology of Marine Models, Station Biologique de Roscoff, Roscoff, France; CNRS, UMR 8227, Integrative Biology of Marine Models, Station Biologique de Roscoff, Roscoff, France.
[Ti] Título:The mannitol utilization system of the marine bacterium Zobellia galactanivorans.
[So] Source:Appl Environ Microbiol;81(5):1799-812, 2015 Mar.
[Is] ISSN:1098-5336
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mannitol is a polyol that occurs in a wide range of living organisms, where it fulfills different physiological roles. In particular, mannitol can account for as much as 20 to 30% of the dry weight of brown algae and is likely to be an important source of carbon for marine heterotrophic bacteria. Zobellia galactanivorans (Flavobacteriia) is a model for the study of pathways involved in the degradation of seaweed carbohydrates. Annotation of its genome revealed the presence of genes potentially involved in mannitol catabolism, and we describe here the biochemical characterization of a recombinant mannitol-2-dehydrogenase (M2DH) and a fructokinase (FK). Among the observations, the M2DH of Z. galactanivorans was active as a monomer, did not require metal ions for catalysis, and featured a narrow substrate specificity. The FK characterized was active on fructose and mannose in the presence of a monocation, preferentially K(+). Furthermore, the genes coding for these two proteins were adjacent in the genome and were located directly downstream of three loci likely to encode an ATP binding cassette (ABC) transporter complex, suggesting organization into an operon. Gene expression analysis supported this hypothesis and showed the induction of these five genes after culture of Z. galactanivorans in the presence of mannitol as the sole source of carbon. This operon for mannitol catabolism was identified in only 6 genomes of Flavobacteriaceae among the 76 publicly available at the time of the analysis. It is not conserved in all Bacteroidetes; some species contain a predicted mannitol permease instead of a putative ABC transporter complex upstream of M2DH and FK ortholog genes.
[Mh] Termos MeSH primário: Flavobacteriaceae/enzimologia
Flavobacteriaceae/metabolismo
Manitol/metabolismo
Redes e Vias Metabólicas/genética
[Mh] Termos MeSH secundário: Carbono/metabolismo
Ativadores de Enzimas/metabolismo
Flavobacteriaceae/genética
Frutoquinases/genética
Frutoquinases/metabolismo
Perfilação da Expressão Gênica
Ordem dos Genes
Íons/metabolismo
Manitol Desidrogenases/genética
Manitol Desidrogenases/metabolismo
Metais/metabolismo
Óperon
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Enzyme Activators); 0 (Ions); 0 (Metals); 0 (Recombinant Proteins); 3OWL53L36A (Mannitol); 7440-44-0 (Carbon); EC 1.1.- (Mannitol Dehydrogenases); EC 2.7.1.- (Fructokinases); EC 2.7.1.4 (fructokinase)
[Em] Mês de entrada:1510
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:141231
[St] Status:MEDLINE
[do] DOI:10.1128/AEM.02808-14


  7 / 148 MEDLINE  
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[PMID]:25537269
[Au] Autor:Ye Y; Fang F; Li Y
[Ad] Endereço:Department of Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, PR China. Electronic address: yeyong@scut.edu.cn.
[Ti] Título:Synthesis and anti-biofilm activities of dihydro-pyrrol-2-one derivatives on Pseudomonas aeruginosa.
[So] Source:Bioorg Med Chem Lett;25(3):597-601, 2015 Feb 01.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Biofilm formation is an important reason for bacterial resistance to antimicrobials. Many compounds with dihydro-pyrrol-2-one (DPO) have antibacterial effects. It is prospective to base on DPO skeleton to design new compounds for biofilm inhibition. DPO was designed by a novel method of tandem cyclization between ethyl glyoxalate and amines, the series of DPO derivatives were synthesized by change of the amines. Their activities were evaluated by the inhibition of biofilm in Pseudomonas aeruginosa. The interaction of DPO derivatives with mannitol dehydrogenase (MDH) or extracellular DNA (eDNA) in the biofilm was simulated by molecular docking to reveal possible mechanism. 19 new DPO derivatives were synthesized and identified, 15 of them had antibacterial activities, but only 5 of them had more than 50% inhibition on biofilm of P. aeruginosa at 50µg/mL. The MDH activity and eDNA content in biofilm decreased significantly after treatment of the DPO derivatives in concentration dependence. The simulation reveals that strong interaction exists between the five DPO derivatives and MDH or eDNA, which are involved in anti-biofilm mechanism. The synthetic method of DPO derivatives is practical to provide effective anti-biofilm agents for P. aeruginosa, and they take effect through inhibition on MDH and eDNA of biofilm.
[Mh] Termos MeSH primário: Biofilmes/efeitos dos fármacos
Pseudomonas aeruginosa/efeitos dos fármacos
Pseudomonas aeruginosa/fisiologia
Pirróis/química
Pirróis/farmacologia
[Mh] Termos MeSH secundário: Antibacterianos/síntese química
Antibacterianos/química
Antibacterianos/farmacologia
Proteínas de Bactérias/antagonistas & inibidores
Proteínas de Bactérias/metabolismo
Sítios de Ligação
DNA/química
DNA/metabolismo
Manitol Desidrogenases/antagonistas & inibidores
Manitol Desidrogenases/metabolismo
Simulação de Acoplamento Molecular
Conformação de Ácido Nucleico
Estrutura Terciária de Proteína
Pirróis/síntese química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Bacterial Proteins); 0 (Pyrroles); 9007-49-2 (DNA); EC 1.1.- (Mannitol Dehydrogenases)
[Em] Mês de entrada:1509
[Cu] Atualização por classe:150116
[Lr] Data última revisão:
150116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:141225
[St] Status:MEDLINE


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[PMID]:25417825
[Au] Autor:Du C; Yi X; Liu W; Han T; Liu Z; Ding Z; Zheng Z; Piao Y; Yuan J; Han Y; Xie M; Xie X
[Ti] Título:MTDH mediates trastuzumab resistance in HER2 positive breast cancer by decreasing PTEN expression through an NFκB-dependent pathway.
[So] Source:BMC Cancer;14:869, 2014 Nov 24.
[Is] ISSN:1471-2407
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Trastuzumab resistance is almost inevitable in the management of human epidermal growth factor receptor (HER) 2 positive breast cancer, in which phosphatase and tensin homolog deleted from chromosome 10 (PTEN) loss is implicated. Since metadherin (MTDH) promotes malignant phenotype of breast cancer, we sought to define whether MTDH promotes trastuzumab resistance by decreasing PTEN expression through an NFκB-dependent pathway. METHODS: The correlations between MTDH and PTEN expressions were analyzed both in HER2 positive breast cancer tissues and trastuzumab resistant SK-BR-3 (SK-BR-3/R) cells. Gene manipulations of MTDH and PTEN levels by knockdown or overexpression were utilized to elucidate molecular mechanisms of MTDH and PTEN implication in trastuzumab resistance. For in vivo studies, SK-BR-3 and SK-BR-3/R cells and modified derivatives were inoculated into nude mice alone or under trastuzumab exposure. Tumor volumes, histological examinations as well as Ki67 and PTEN expressions were revealed. RESULTS: Elevated MTDH expression indicated poor clinical benefit, shortened progression free survival time, and was negatively correlated with PTEN level both in HER2 positive breast cancer patients and SK-BR-3/R cells. MTDH knockdown restored PTEN expression and trastuzumab sensitivity in SK-BR-3/R cells, while MTDH overexpression prevented SK-BR-3 cell death under trastuzumab exposure, probably through IκBα inhibition and nuclear translocation of p65 which subsequently decreased PTEN expression. Synergized effect of PTEN regulation were observed upon MTDH and p65 co-transfection. Forced PTEN expression in SK-BR-3/R cells restored trastuzumab sensitivity. Furthermore, decreased tumor volume and Ki67 level as well as increased PTEN expression were observed after MTDH knockdown in subcutaneous breast cancer xenografts from SK-BR-3/R cells, while the opposite effect were found in grafts from MTDH overexpressing SK-BR-3 cells. CONCLUSIONS: MTDH overexpression confers trastuzumab resistance in HER2 positive breast cancer. MTDH mediates trastuzumab resistance, at least in part, by PTEN inhibition through an NFκB-dependent pathway, which may be utilized as a promising therapeutic target for HER2 positive breast cancer.
[Mh] Termos MeSH primário: Neoplasias da Mama/genética
Neoplasias da Mama/metabolismo
Resistência a Medicamentos Antineoplásicos
Manitol Desidrogenases/metabolismo
NF-kappa B/metabolismo
PTEN Fosfo-Hidrolase/genética
Receptor ErbB-2/metabolismo
[Mh] Termos MeSH secundário: Adulto
Idoso
Animais
Anticorpos Monoclonais Humanizados/farmacologia
Neoplasias da Mama/patologia
Linhagem Celular Tumoral
Modelos Animais de Doenças
Feminino
Expressão Gênica
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Xenoenxertos
Seres Humanos
Manitol Desidrogenases/genética
Camundongos
Meia-Idade
Gradação de Tumores
Estadiamento de Neoplasias
Receptor ErbB-2/genética
Transdução de Sinais/efeitos dos fármacos
Trastuzumab
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibodies, Monoclonal, Humanized); 0 (NF-kappa B); EC 1.1.- (Mannitol Dehydrogenases); EC 1.1.1.138 (mannitol 2-dehydrogenase (NADP)); EC 2.7.10.1 (Receptor, ErbB-2); EC 3.1.3.67 (PTEN Phosphohydrolase); EC 3.1.3.67 (PTEN protein, human); P188ANX8CK (Trastuzumab)
[Em] Mês de entrada:1507
[Cu] Atualização por classe:161125
[Lr] Data última revisão:
161125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:141125
[St] Status:MEDLINE
[do] DOI:10.1186/1471-2407-14-869


  9 / 148 MEDLINE  
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[PMID]:25405925
[Au] Autor:Velez-Vega C; McKay DJ; Aravamuthan V; Pearlstein R; Duca JS
[Ad] Endereço:Computer-Aided Drug Discovery, Global Discovery Chemistry, Novartis Institutes for BioMedical Research , 100 Technology Square, Cambridge, Massachusetts 02139, United States.
[Ti] Título:Time-averaged distributions of solute and solvent motions: exploring proton wires of GFP and PfM2DH.
[So] Source:J Chem Inf Model;54(12):3344-61, 2014 Dec 22.
[Is] ISSN:1549-960X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Proton translocation pathways of selected variants of the green fluorescent protein (GFP) and Pseudomonas fluorescens mannitol 2-dehydrogenase (PfM2DH) were investigated via an explicit solvent molecular dynamics-based analysis protocol that allows for direct quantitative relationship between a crystal structure and its time-averaged solute-solvent structure obtained from simulation. Our study of GFP is in good agreement with previous research suggesting that the proton released from the chromophore upon photoexcitation can diffuse through an extended internal hydrogen bonding network that allows for the proton to exit to bulk or be recaptured by the anionic chromophore. Conversely for PfM2DH, we identified the most probable ionization states of key residues along the proton escape channel from the catalytic site to bulk solvent, wherein the solute and high-density solvent crystal structures of binary and ternary complexes were properly reproduced. Furthermore, we proposed a plausible mechanism for this proton translocation process that is consistent with the state-dependent structural shifts observed in our analysis. The time-averaged structures generated from our analyses facilitate validation of MD simulation results and provide a comprehensive profile of the dynamic all-occupancy solvation network within and around a flexible solute, from which detailed hydrogen-bonding networks can be inferred. In this way, potential drawbacks arising from the elucidation of these networks by examination of static crystal structures or via alternate rigid-protein solvation analysis procedures can be overcome. Complementary studies aimed at the effective use of our methodology for alternate implementations (e.g., ligand design) are currently underway.
[Mh] Termos MeSH primário: Proteínas de Fluorescência Verde/química
Manitol Desidrogenases/química
Simulação de Dinâmica Molecular
Movimento
Prótons
Solventes/química
[Mh] Termos MeSH secundário: Domínio Catalítico
Cristalografia por Raios X
Proteínas de Fluorescência Verde/genética
Proteínas de Fluorescência Verde/metabolismo
Manitol Desidrogenases/genética
Manitol Desidrogenases/metabolismo
Mutação
Estrutura Secundária de Proteína
Pseudomonas fluorescens/enzimologia
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Protons); 0 (Solvents); 147336-22-9 (Green Fluorescent Proteins); EC 1.1.- (Mannitol Dehydrogenases)
[Em] Mês de entrada:1507
[Cu] Atualização por classe:141222
[Lr] Data última revisão:
141222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:141119
[St] Status:MEDLINE
[do] DOI:10.1021/ci500571h


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[PMID]:24830763
[Au] Autor:Shao Z; Zhang P; Li Q; Wang X; Duan D
[Ad] Endereço:Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China; University of the Chinese Academy of Sciences, Beijing, China.
[Ti] Título:Characterization of mannitol-2-dehydrogenase in Saccharina japonica: evidence for a new polyol-specific long-chain dehydrogenases/reductase.
[So] Source:PLoS One;9(5):e97935, 2014.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mannitol plays a crucial role in brown algae, acting as carbon storage, organic osmolytes and antioxidant. Transcriptomic analysis of Saccharina japonica revealed that the relative genes involved in the mannitol cycle are existent. Full-length sequence of mannitol-2-dehydrogenase (M2DH) gene was obtained, with one open reading frame of 2,007 bp which encodes 668 amino acids. Cis-regulatory elements for response to methyl jasmonic acid, light and drought existed in the 5'-upstream region. Phylogenetic analysis indicated that SjM2DH has an ancient prokaryotic origin, and is probably acquired by horizontal gene transfer event. Multiple alignment and spatial structure prediction displayed a series of conserved functional residues, motifs and domains, which favored that SjM2DH belongs to the polyol-specific long-chain dehydrogenases/reductase (PSLDR) family. Expressional profiles of SjM2DH in the juvenile sporophytes showed that it was influenced by saline, oxidative and desiccative factors. SjM2DH was over-expressed in Escherichia coli, and the cell-free extracts with recombinant SjM2DH displayed high activity on D-fructose reduction reaction. The analysis on SjM2DH gene structure and biochemical parameters reached a consensus that activity of SjM2DH is NADH-dependent and metal ion-independent. The characterization of SjM2DH showed that M2DH is a new member of PSLDR family and play an important role in mannitol metabolism in S. japonica.
[Mh] Termos MeSH primário: Laminaria/enzimologia
Manitol Desidrogenases/genética
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Domínio Catalítico
Frutose/química
Regulação Enzimológica da Expressão Gênica
Peróxido de Hidrogênio/farmacologia
Manitol Desidrogenases/biossíntese
Manitol Desidrogenases/química
Modelos Moleculares
Dados de Sequência Molecular
Oxirredução
Filogenia
Estrutura Secundária de Proteína
Salinidade
Homologia Estrutural de Proteína
Especificidade por Substrato
Transcrição Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
30237-26-4 (Fructose); BBX060AN9V (Hydrogen Peroxide); EC 1.1.- (Mannitol Dehydrogenases)
[Em] Mês de entrada:1506
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140517
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0097935



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