Base de dados : MEDLINE
Pesquisa : G02.111.158.812 [Categoria DeCS]
Referências encontradas : 28842 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 2885 ir para página                         

  1 / 28842 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28460451
[Au] Autor:Tsitsipatis D; Jayavelu AK; Müller JP; Bauer R; Schmidt-Arras D; Mahboobi S; Schnöder TM; Heidel F; Böhmer FD
[Ad] Endereço:Institute of Molecular Cell Biology, CMB, Jena University Hospital, Jena, Germany.
[Ti] Título:Synergistic killing of FLT3ITD-positive AML cells by combined inhibition of tyrosine-kinase activity and N-glycosylation.
[So] Source:Oncotarget;8(16):26613-26624, 2017 Apr 18.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Fms-like tyrosine kinase 3 (FLT3) with internal tandem duplications (ITD) is a major oncoprotein in acute myeloid leukemia (AML), and confers an unfavorable prognosis. Interference with FLT3ITD signaling is therefore pursued as a promising therapeutic strategy. In this study we show that abrogation of FLT3ITD glycoprotein maturation using low doses of the N-glycosylation inhibitor tunicamycin has anti-proliferative and pro-apoptotic effects on FLT3ITD-expressing human and murine cell lines. This effect is mediated in part by arresting FLT3ITD in an underglycosylated state and thereby attenuating FLT3ITD-driven AKT and ERK signaling. In addition, tunicamycin caused pronounced endoplasmatic reticulum stress and apoptosis through activation of protein kinase RNA-like endoplasmic reticulum kinase (PERK) and activation of the gene encoding CCAAT-enhancer-binding protein homologous protein (CHOP). PERK inhibition with a small molecule attenuated CHOP induction and partially rescued cells from apoptosis. Combination of tunicamycin with potent FLT3ITD kinase inhibitors caused synergistic cell killing, which was highly selective for cell lines and primary AML cells expressing FLT3ITD. Although tunicamycin is currently not a clinically applicable drug, we propose that mild inhibition of N-glycosylation may have therapeutic potential in combination with FLT3 kinase inhibitors for FLT3ITD-positive AML.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Duplicação Gênica
Leucemia Mieloide Aguda/genética
Inibidores de Proteínas Quinases/farmacologia
Sequências de Repetição em Tandem
Tirosina Quinase 3 Semelhante a fms/genética
[Mh] Termos MeSH secundário: Apoptose/efeitos dos fármacos
Apoptose/genética
Linhagem Celular Tumoral
Sinergismo Farmacológico
Estresse do Retículo Endoplasmático
MAP Quinases Reguladas por Sinal Extracelular/metabolismo
Expressão Gênica
Glicosilação/efeitos dos fármacos
Seres Humanos
Leucemia Mieloide Aguda/tratamento farmacológico
Leucemia Mieloide Aguda/metabolismo
Leucemia Mieloide Aguda/patologia
Proteínas Proto-Oncogênicas c-akt/metabolismo
Células Tumorais Cultivadas
Tunicamicina/farmacologia
Tirosina Quinase 3 Semelhante a fms/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Protein Kinase Inhibitors); 11089-65-9 (Tunicamycin); EC 2.7.10.1 (fms-Like Tyrosine Kinase 3); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.15772


  2 / 28842 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29329339
[Au] Autor:Granger BL
[Ad] Endereço:Department of Microbiology and Immunology, Montana State University, Bozeman, Montana, United States of America.
[Ti] Título:Accessibility and contribution to glucan masking of natural and genetically tagged versions of yeast wall protein 1 of Candida albicans.
[So] Source:PLoS One;13(1):e0191194, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Yeast wall protein 1 (Ywp1) is an abundant glycoprotein of the cell wall of the yeast form of Candida albicans, the most prevalent fungal pathogen of humans. Antibodies that bind to the polypeptide backbone of isolated Ywp1 show little binding to intact yeast cells, presumably because the Ywp1 epitopes are masked by the polysaccharides of the mannoproteins that form the outer layer of the cell wall. Rare cells do exhibit much greater anti-Ywp1 binding, however, and one of these was isolated and characterized. No differences were seen in its Ywp1, but it exhibited greater adhesiveness, sensitivity to wall perturbing agents, and exposure of its underlying ß-1,3-glucan layer to external antibodies. The molecular basis for this greater epitope accessibility has not been determined, but has facilitated exploration of how these properties change as a function of cell growth and morphology. In addition, previously engineered strains with reduced quantities of Ywp1 in their cell walls were also found to have greater ß-1,3-glucan exposure, indicating that Ywp1 itself contributes to the masking of wall epitopes, which may be important for understanding the anti-adhesive effect of Ywp1. Ectopic production of Ywp1 by hyphae, which reduces the adhesivity of these filamentous forms of C. albicans, was similarly found to reduce exposure of the ß-1,3-glucan in their walls. To monitor Ywp1 in the cell wall irrespective of its accessibility, green fluorescent protein (Gfp) was genetically inserted into wall-anchored Ywp1 using a bifunctional cassette that also allowed production from a single transfection of a soluble, anchor-free version. The wall-anchored Ywp1-Gfp-Ywp1 accumulated in the wall of the yeast forms but not hyphae, and appeared to have properties similar to native Ywp1, including its adhesion-inhibiting effect. Some pseudohyphal walls also detectably accumulated this probe. Strains of C. albicans with tandem hemagglutinin (HA) epitopes inserted into wall-anchored Ywp1 were previously created by others, and were further explored here. As above, rare cells with much greater accessibility of the HA epitopes were isolated, and also found to exhibit greater exposure of Ywp1 and ß-1,3-glucan. The placement of the HA cassette inhibited the normal N-glycosylation and propeptide cleavage of Ywp1, but the wall-anchored Ywp1-HA-Ywp1 still accumulated in the cell wall of yeast forms. Bifunctional transformation cassettes were used to additionally tag these molecules with Gfp, generating soluble Ywp1-HA-Gfp and wall-anchored Ywp1-HA-Gfp-Ywp1 molecules. The former revealed unexpected electrophoretic properties caused by the HA insertion, while the latter further highlighted differences between the presence of a tagged Ywp1 molecule (as revealed by Gfp fluorescence) and its accessibility in the cell wall to externally applied antibodies specific for HA, Gfp and Ywp1, with accessibility being greatest in the rapidly expanding walls of budding daughter cells. These strains and results increase our understanding of cell wall properties and how C. albicans masks itself from recognition by the human immune system.
[Mh] Termos MeSH primário: Candida albicans/genética
Candida albicans/metabolismo
Proteínas Fúngicas/genética
Proteínas Fúngicas/metabolismo
beta-Glucanas/metabolismo
[Mh] Termos MeSH secundário: Anticorpos Antifúngicos
Antígenos de Fungos/química
Antígenos de Fungos/genética
Antígenos de Fungos/metabolismo
Candida albicans/imunologia
Parede Celular/genética
Parede Celular/imunologia
Parede Celular/metabolismo
Epitopos/química
Epitopos/genética
Epitopos/metabolismo
Proteínas Fúngicas/imunologia
Glicosilação
Proteínas de Fluorescência Verde/genética
Proteínas de Fluorescência Verde/imunologia
Proteínas de Fluorescência Verde/metabolismo
Hemaglutininas/genética
Hemaglutininas/imunologia
Hemaglutininas/metabolismo
Seres Humanos
Glicoproteínas de Membrana/genética
Glicoproteínas de Membrana/imunologia
Glicoproteínas de Membrana/metabolismo
Engenharia de Proteínas
Proteínas Recombinantes de Fusão/genética
Proteínas Recombinantes de Fusão/imunologia
Proteínas Recombinantes de Fusão/metabolismo
beta-Glucanas/química
beta-Glucanas/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Fungal); 0 (Antigens, Fungal); 0 (Epitopes); 0 (Fungal Proteins); 0 (Hemagglutinins); 0 (Membrane Glycoproteins); 0 (Recombinant Fusion Proteins); 0 (beta-Glucans); 0 (mannoproteins); 147336-22-9 (Green Fluorescent Proteins); 9051-97-2 (beta-1,3-glucan)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180113
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191194


  3 / 28842 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29315346
[Au] Autor:Carvalho SB; Moreira AS; Gomes J; Carrondo MJT; Thornton DJ; Alves PM; Costa J; Peixoto C
[Ad] Endereço:iBET, Instituto de Biologia Experimental e Tecnológica, Oeiras, Portugal.
[Ti] Título:A detection and quantification label-free tool to speed up downstream processing of model mucins.
[So] Source:PLoS One;13(1):e0190974, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mucins are high-molecular weight glycoproteins (0.25-20 MDa) containing one or more domains that are heavily O-glycosylated. Their implications as targets for cancer treatment have increased the interest in these glycoproteins, mainly in the fields of vaccines and antibodies. However, mucins present high heterogeneity, posing challenges that affect purification processes and quality control analysis. In that sense, it is necessary to develop and improve downstream processes and analytical methods to characterize these products. Here a tool based on biolayer interferometry analysis to improve mucin's detection and quantification in a fast, simple and label free-way is presented. Taking advantage of lectin recognition of mucins' carbohydrate structures, several lectins were evaluated and immobilized on streptavidin biosensors. Different assay conditions were optimized and the most suitable lectin, Aleuria aurantia lectin (AAL), was selected. Bovine Submaxillary Gland and human MUC5B mucins were used as proof of concept and were successfully detected and quantified at different stages of purification. High sensitivity levels were achieved with LOD and LOQ of 3.8 µg mL-1 and 11.7 µg mL-1 for BSM, and 0.2 µg mL-1 and 0.6 µg mL-1 for MUC5B. AAL binding specificity was also confirmed with fucose competition assays. Our method represents an advance on mucins detection and quantification since the existing methods present several disadvantages for process development. Hereafter, it can be applied to the optimization of new or already established downstream processes for mucins' purification.
[Mh] Termos MeSH primário: Modelos Moleculares
Mucinas/metabolismo
[Mh] Termos MeSH secundário: Cromatografia em Gel
Eletroforese em Gel de Poliacrilamida
Glicosilação
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Mucins)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180110
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190974


  4 / 28842 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28467637
[Au] Autor:Li X; Zhou M; Huang W; Yang H
[Ad] Endereço:Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
[Ti] Título:N-glycosylation of the ß adrenergic receptor regulates receptor function by modulating dimerization.
[So] Source:FEBS J;284(13):2004-2018, 2017 07.
[Is] ISSN:1742-4658
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:N-glycosylation is a common post-translational modification of G-protein-coupled receptors (GPCRs). However, it remains unknown how N-glycosylation affects GPCR signaling. ß adrenergic receptor (ß AR) has three N-glycosylation sites: Asn6, Asn15 at the N-terminus, and Asn187 at the second extracellular loop (ECL2). Here, we show that deletion of the N-glycan did not affect receptor expression and ligand binding. Deletion of the N-glycan at the N-terminus rather than Asn187 showed decreased effects on isoproterenol-promoted G-protein-dependent signaling, ß-arrestin2 recruitment, and receptor internalization. Both N6Q and N15Q showed decreased receptor dimerization, while N187Q did not influence receptor dimerization. As decreased ß AR homodimer accompanied with reduced efficiency for receptor function, we proposed that the N-glycosylation of ß AR regulated receptor function by influencing receptor dimerization. To verify this hypothesis, we further paid attention to the residues at the dimerization interface. Studies of Lys60 and Glu338, two residues at the receptor dimerization interface, exhibited that the K60A/E338A showed decreased ß AR dimerization and its effects on receptor signaling were similar to N6Q and N15Q, which further supported the importance of receptor dimerization for receptor function. This work provides new insights into the relationship among glycosylation, dimerization, and function of GPCRs. ENZYMES: Peptide-N-glycosidase F (PNGase F, EC 3.2.2.11); endo-ß-N-acetylglucosaminidase A (Endo-A, EC 3.2.1.96).
[Mh] Termos MeSH primário: Multimerização Proteica
Receptores Adrenérgicos beta 2/química
Receptores Adrenérgicos beta 2/metabolismo
Transdução de Sinais
[Mh] Termos MeSH secundário: Agonistas Adrenérgicos beta/farmacologia
Sítios de Ligação/genética
Western Blotting
Endocitose/efeitos dos fármacos
Glicosilação
Células HEK293
Seres Humanos
Isoproterenol/farmacologia
Microscopia Confocal
Mutação
Polissacarídeos/metabolismo
Processamento de Proteína Pós-Traducional
Receptores Adrenérgicos beta 2/genética
beta-Arrestinas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Adrenergic beta-Agonists); 0 (Polysaccharides); 0 (Receptors, Adrenergic, beta-2); 0 (beta-Arrestins); L628TT009W (Isoproterenol)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1111/febs.14098


  5 / 28842 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Bartolini, Paolo
Texto completo
[PMID]:29179059
[Au] Autor:Dias PVS; Arthuso FS; Oliveira JE; Suzuki MF; Sousa JM; Ribela MTCP; Bartolini P; Soares CRJ
[Ad] Endereço:Biotechnology Center, Instituto de Pesquisas Energéticas e Nucleares, IPEN - CNEN/SP, São Paulo, Brazil.
[Ti] Título:Determination of recombinant Interferon-α2 in E. coli periplasmic extracts by reversed-phase high-performance liquid chromatography.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1072:193-198, 2018 Jan 01.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Reversed-phase high-performance liquid chromatography (RP-HPLC) has been used to analyze Interferon α-2 (IFN-α2) as a pure protein or as a pharmaceutical preparation: a method for analyzing periplasmic IFN-α2 directly in osmotic shock extract has, however, never been reported. This work describes an RP-HPLC methodology for the qualitative and quantitative analysis of human IFN-α2a and IFN-α2b directly in bacterial periplasmic extracts or in purified preparations. The analytical method has been set up and validated for accuracy, precision, linearity, sensitivity and specificity. A recovery test indicated an average bias of ∼1%, intra-day and inter-day quantitative determinations presented relative standard deviations always≤5%, while the working sensitivity was of ∼0.3µg of IFN-α2 (RSD=5%). The method proved to be suitable for detecting and quantifying also glycosylated and oxidized forms and N-methionylated IFN-α2 molecules, it was, however, not able to distinguish between IFN-α2a and IFN-α2b. This rapid methodology allows the application of RP-HPLC as a powerful tool to monitor the production yield and quality of IFN-α2 in osmotic shock fluids, right after, or even during the fermentation process.
[Mh] Termos MeSH primário: Cromatografia Líquida de Alta Pressão/métodos
Cromatografia de Fase Reversa/métodos
Escherichia coli/genética
Interferon-alfa/análise
Proteínas Recombinantes/análise
[Mh] Termos MeSH secundário: Glicosilação
Seres Humanos
Interferon-alfa/química
Interferon-alfa/genética
Interferon-alfa/isolamento & purificação
Modelos Lineares
Oxirredução
Periplasma/metabolismo
Proteínas Recombinantes/química
Proteínas Recombinantes/genética
Proteínas Recombinantes/isolamento & purificação
Reprodutibilidade dos Testes
Sensibilidade e Especificidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (IFNA2 protein, human); 0 (Interferon-alpha); 0 (Recombinant Proteins)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE


  6 / 28842 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29297994
[Au] Autor:Karaulov AV; Gurina NN; Novikov DV; Fomina SG; Novikov VV
[Ti] Título:Role of MUC1 Expression in Tumor Progression.
[So] Source:Vestn Ross Akad Med Nauk;71(5):392-6, 2016.
[Is] ISSN:0869-6047
[Cp] País de publicação:Russia (Federation)
[La] Idioma:eng
[Ab] Resumo:Mucin 1 (MUC1) is a multistructural and multifunctional protein that is involved in regulating diverse cellular activities. This strongly glycosylated transmembrane protein forms a mucous gel on the surface of epithelial cells that protects the cells from injury. MUC1 acts as a signaling molecule and transcription factor modulating metabolism and resistance to bacterial-induced inflammation. This article presents a review of the relationship between structural and functional changes of the MUC1 and the characteristics of cancer cells. The alteration in MUC1 expression level, a number of structural forms, protein glycosylation and localization occurs in cancer cells. These alterations lead to metabolic reprogramming associated with proliferation, resistance to hypoxia and angiogenesis which affects the survival of cancer cells. Furthermore, cancer cells can take advantage of MUC1 interaction with adhesion molecules for invasion and metastasis. Thus, MUC1 plays a key role both in the homeostasis of epithelial cells and in cancer progression. Understanding the role of MUC1 expression in tumor cells survival is important for the development of new monitoring and therapeutic approaches for the treatment MUC1 positive maligancies.
[Mh] Termos MeSH primário: Mucina-1/metabolismo
Neoplasias
[Mh] Termos MeSH secundário: Progressão da Doença
Glicosilação
Seres Humanos
Neoplasias/metabolismo
Neoplasias/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (MUC1 protein, human); 0 (Mucin-1)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180104
[St] Status:MEDLINE
[do] DOI:10.15690/vramn736


  7 / 28842 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28470609
[Au] Autor:Strutton B; Jaffé SRP; Pandhal J; Wright PC
[Ad] Endereço:Department of Chemical and Biological Engineering, ChELSI Institute, University of Sheffield, Mappin Street, Sheffield, S1 3JD, UK.
[Ti] Título:Generation of Recombinant N-Linked Glycoproteins in E. coli.
[So] Source:Methods Mol Biol;1586:233-250, 2017.
[Is] ISSN:1940-6029
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The production of N-linked recombinant glycoproteins is possible in a variety of biotechnology host cells, and more recently in the bacterial workhorse, Escherichia coli. This methods chapter will outline the components and procedures needed to produce N-linked glycoproteins in E. coli, utilizing Campylobacter jejuni glycosylation machinery, although other related genes can be used with minimal tweaks to this methodology. To ensure a successful outcome, various methods will be highlighted that can confirm glycoprotein production to a high degree of confidence, including the gold standard of mass spectrometry analysis.
[Mh] Termos MeSH primário: Campylobacter jejuni/genética
Escherichia coli/genética
Glicoproteínas/genética
Interferon-alfa/genética
[Mh] Termos MeSH secundário: Far-Western Blotting/métodos
Clonagem Molecular/métodos
Eletroforese em Gel de Poliacrilamida/métodos
Genes Bacterianos
Glicoproteínas/química
Glicoproteínas/isolamento & purificação
Glicosilação
Interferon-alfa/química
Interferon-alfa/isolamento & purificação
Espectrometria de Massas/métodos
Plasmídeos/genética
Polissacarídeos/análise
Polissacarídeos/genética
Processamento de Proteína Pós-Traducional
Proteínas Recombinantes/química
Proteínas Recombinantes/genética
Proteínas Recombinantes/isolamento & purificação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Glycoproteins); 0 (Interferon-alpha); 0 (Polysaccharides); 0 (Recombinant Proteins); 43K1W2T1M6 (interferon alfa-2b)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1007/978-1-4939-6887-9_15


  8 / 28842 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29334926
[Au] Autor:Ghelani H; Razmovski-Naumovski V; Pragada RR; Nammi S
[Ad] Endereço:School of Science and Health, Western Sydney University, Sydney, NSW, 2751, Australia.
[Ti] Título:(R)-α-Lipoic acid inhibits fructose-induced myoglobin fructation and the formation of advanced glycation end products (AGEs) in vitro.
[So] Source:BMC Complement Altern Med;18(1):13, 2018 Jan 15.
[Is] ISSN:1472-6882
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Fructose-mediated protein glycation (fructation) has been linked to an increase in diabetic and cardiovascular complications due to over consumption of high-fructose containing diets in recent times. The objective of the present study is to evaluate the protective effect of (R)-α-lipoic acid (ALA) against fructose-induced myoglobin fructation and the formation of advanced glycation end products (AGEs) in vitro. METHODS: The anti-glycation activity of ALA was determined using the formation of AGEs fluorescence intensity, iron released from the heme moiety of myoglobin and the level of fructosamine. The fructation-induced myoglobin oxidation was examined using the level of protein carbonyl content and thiol group estimation. RESULTS: The results showed that co-incubation of myoglobin (1 mg/mL), fructose (1 M) and ALA (1, 2 and 4 mM) significantly inhibited the formation of AGEs during the 30 day study period. ALA markedly decreased the levels of fructosamine, which is directly associated with the reduction of AGEs formation. Furthermore, ALA significantly reduced free iron release from myoglobin which is attributed to the protection of myoglobin from fructose-induced glycation. The results also demonstrated a significant protective effect of ALA on myoglobin oxidative damages, as seen from decreased protein carbonyl content and increased protein thiols. CONCLUSION: These findings provide new insights into the anti-glycation properties of ALA and emphasize that ALA supplementation is beneficial in the prevention of AGEs-mediated diabetic and cardiovascular complications.
[Mh] Termos MeSH primário: Frutose/metabolismo
Produtos Finais de Glicação Avançada/metabolismo
Glicosilação/efeitos dos fármacos
Mioglobina/metabolismo
Ácido Tióctico/farmacologia
[Mh] Termos MeSH secundário: Animais
Produtos Finais de Glicação Avançada/análise
Mioglobina/análise
Mioglobina/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Glycation End Products, Advanced); 0 (Myoglobin); 30237-26-4 (Fructose); 73Y7P0K73Y (Thioctic Acid)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180117
[St] Status:MEDLINE
[do] DOI:10.1186/s12906-017-2076-6


  9 / 28842 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29371602
[Au] Autor:Gélinas R; Mailleux F; Dontaine J; Bultot L; Demeulder B; Ginion A; Daskalopoulos EP; Esfahani H; Dubois-Deruy E; Lauzier B; Gauthier C; Olson AK; Bouchard B; Des Rosiers C; Viollet B; Sakamoto K; Balligand JL; Vanoverschelde JL; Beauloye C; Horman S; Bertrand L
[Ad] Endereço:Pole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, 1200, Belgium.
[Ti] Título:AMPK activation counteracts cardiac hypertrophy by reducing O-GlcNAcylation.
[So] Source:Nat Commun;9(1):374, 2018 01 25.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:AMP-activated protein kinase (AMPK) has been shown to inhibit cardiac hypertrophy. Here, we show that submaximal AMPK activation blocks cardiomyocyte hypertrophy without affecting downstream targets previously suggested to be involved, such as p70 ribosomal S6 protein kinase, calcineurin/nuclear factor of activated T cells (NFAT) and extracellular signal-regulated kinases. Instead, cardiomyocyte hypertrophy is accompanied by increased protein O-GlcNAcylation, which is reversed by AMPK activation. Decreasing O-GlcNAcylation by inhibitors of the glutamine:fructose-6-phosphate aminotransferase (GFAT), blocks cardiomyocyte hypertrophy, mimicking AMPK activation. Conversely, O-GlcNAcylation-inducing agents counteract the anti-hypertrophic effect of AMPK. In vivo, AMPK activation prevents myocardial hypertrophy and the concomitant rise of O-GlcNAcylation in wild-type but not in AMPKα2-deficient mice. Treatment of wild-type mice with O-GlcNAcylation-inducing agents reverses AMPK action. Finally, we demonstrate that AMPK inhibits O-GlcNAcylation by mainly controlling GFAT phosphorylation, thereby reducing O-GlcNAcylation of proteins such as troponin T. We conclude that AMPK activation prevents cardiac hypertrophy predominantly by inhibiting O-GlcNAcylation.
[Mh] Termos MeSH primário: Proteínas Quinases Ativadas por AMP/genética
Acetilglucosamina/metabolismo
Cardiomegalia/genética
Miocárdio/metabolismo
Miócitos Cardíacos/metabolismo
Transferases de Grupos Nitrogenados/genética
[Mh] Termos MeSH secundário: Proteínas Quinases Ativadas por AMP/deficiência
Acetilglucosamina/farmacologia
Acilação/efeitos dos fármacos
Animais
Animais Recém-Nascidos
Azasserina/farmacologia
Compostos Azo/farmacologia
Cardiomegalia/metabolismo
Cardiomegalia/patologia
Ativação Enzimática/efeitos dos fármacos
Ativadores de Enzimas/farmacologia
Regulação da Expressão Gênica
Glicosilação/efeitos dos fármacos
Ventrículos do Coração/efeitos dos fármacos
Ventrículos do Coração/metabolismo
Ventrículos do Coração/patologia
Masculino
Camundongos
Camundongos Knockout
Miocárdio/patologia
Miócitos Cardíacos/efeitos dos fármacos
Miócitos Cardíacos/patologia
Transferases de Grupos Nitrogenados/antagonistas & inibidores
Transferases de Grupos Nitrogenados/metabolismo
Norleucina/análogos & derivados
Norleucina/farmacologia
Fosforilação/efeitos dos fármacos
Cultura Primária de Células
Pironas/farmacologia
Ratos
Ratos Wistar
Transdução de Sinais
Tiofenos/farmacologia
Troponina T/genética
Troponina T/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (6-diazo-5-oxonorleucine); 0 (A 769662); 0 (Azo Compounds); 0 (Enzyme Activators); 0 (Pyrones); 0 (Thiophenes); 0 (Troponin T); 832C8OV84S (Norleucine); 87299V3Q9W (Azaserine); EC 2.6.- (Nitrogenous Group Transferases); EC 2.6.1.16 (Gfpt1 protein, mouse); EC 2.7.11.1 (AMPK alpha2 subunit, mouse); EC 2.7.11.31 (AMP-Activated Protein Kinases); V956696549 (Acetylglucosamine)
[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:180127
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02795-4


  10 / 28842 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29329315
[Au] Autor:Kumar S; Cieplak P
[Ad] Endereço:SBP Medical Discovery Institute, La Jolla, California, United States of America.
[Ti] Título:Role of N-glycosylation in activation of proMMP-9. A molecular dynamics simulations study.
[So] Source:PLoS One;13(1):e0191157, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Human matrix metalloproteinase proMMP-9 is secreted as latent zymogen, which requires two-steps proteolytic activation. The secreted proMMP-9 is glycosylated at two positions: Asn38 and Asn120 located in the prodomain and catalytic domain, respectively. It has been demonstrated that glycosylation at Asn120 is required for secretion of the enzyme, while the role of Asn38 glycosylation is not well understood, but is usually linked to the activation process. One hypothesis stated that the Asn38 glycosylation might protect against proteolytic activation. However, the activation process occurs with or without the presence of this glycosylation. We conducted molecular dynamics (MD) simulations on the glycosylated and non-glycosylated proMMP-9 to elucidate the effect of Asn38 glycosylation on this two-step activation process. The simulation results suggest that Asn38 glycosylation does not hinder the activation process directly, but induces conformational changes in the vicinity of the first proteolytic region in such a way that E59-M60 cleavage is processed before R106-F107. These results correlate with analysis provided by Boon et al. and experimental data from Ogata et al. who attempted to determine the order of events in activation of proMMP-9. Results from additional MD simulations for the model of glycosylated proMMP-9 bound to galectin-8 N-domain suggest that Gal-8 by interacting with Asn38 glycan might further facilitate processing of the first cleavage between E59-M60. Thus, our simulation results suggest that both Asn38 glycosylation and interaction with Gal-8N may be involved in facilitating and the temporal order of the activation process of pro-MMP9. The aim of this report is to provide an inspiration for future detailed experiments aimed at explaining the role of N-glycosylation in the activation process of prodomain of MMP-9.
[Mh] Termos MeSH primário: Precursores Enzimáticos/metabolismo
Metaloproteinase 9 da Matriz/metabolismo
Simulação de Dinâmica Molecular
[Mh] Termos MeSH secundário: Ativação Enzimática
Glicosilação
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Enzyme Precursors); EC 3.4.24.35 (Matrix Metalloproteinase 9)
[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:180113
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191157



página 1 de 2885 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