Base de dados : MEDLINE
Pesquisa : G02.111.570.820.235 [Categoria DeCS]
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  1 / 10762 MEDLINE  
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[PMID]:28659043
[Au] Autor:Liu X; Zhang J; Guo K; Jia A; Zhang M; Shi Y; Liu C; Xiao L; Sun Z
[Ad] Endereço:a Key Laboratory for Biosensors of Shandong Province , Biology Institute of Shandong Academy of Sciences , Jinan , China.
[Ti] Título:Three new oleanane-type triterpenoid saponins from the seeds of Celosia cristata L.
[So] Source:Nat Prod Res;32(2):167-174, 2018 Jan.
[Is] ISSN:1478-6427
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Phytochemical investigation of the 1-butanol soluble fraction of 60% ethanol extract of the seeds of Celosia cristata L. led to the identification of three new oleanane-type triterpenoid saponins. Using D and D NMR experiment methods, ESI-MS analysis and acid hydrolysis, their structures were identified as 3-O-[ß-D-xylopyranosyl-(1 â†’ 3)-ß-D-glucuronopyranosyl]-2ß-hydroxy-oleanolic acid-28-O-ß-D-glucopyranoside (1), 3-O-[ß-D-xylopyranosyl-(1 â†’ 3)-ß-D-glucuronopyranosyl]-2ß, 23-dihydroxy-oleanolic acid-28-O-ß-D-glucopyranoside (2) and 3-O-[ß-D-glucopyranosyl-(1 â†’ 4)-ß-D-glucopyranosyl]-2-hydroxyl-medicagenic acid-28-O-ß-D-glucopyranosyide (3), respectively.
[Mh] Termos MeSH primário: Celosia/química
Ácido Oleanólico/análogos & derivados
Ácido Oleanólico/isolamento & purificação
Saponinas/isolamento & purificação
[Mh] Termos MeSH secundário: Configuração de Carboidratos
Sequência de Carboidratos
Hidrólise
Espectroscopia de Ressonância Magnética
Estrutura Molecular
Ácido Oleanólico/química
Saponinas/química
Sementes/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Saponins); 0 (oleanane); 6SMK8R7TGJ (Oleanolic Acid)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170630
[St] Status:MEDLINE
[do] DOI:10.1080/14786419.2017.1343317


  2 / 10762 MEDLINE  
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[PMID]:29175728
[Au] Autor:Zhou Y; Zhang B; Stuart-Williams H; Grice K; Hocart CH; Gessler A; Kayler ZE; Farquhar GD
[Ad] Endereço:School of Chemistry & Chemical Engineering, Shaanxi University of Science & Technology, Xi'an, China; Institute for Landscape Biogeochemistry, ZALF, Germany; Leibniz Institute for Freshwater Ecology & Inland Fisheries, Germany. Electronic address: youping.zhou@sust.edu.cn.
[Ti] Título:On the contributions of photorespiration and compartmentation to the contrasting intramolecular H profiles of C and C plant sugars.
[So] Source:Phytochemistry;145:197-206, 2018 Jan.
[Is] ISSN:1873-3700
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Compartmentation of C photosynthetic biochemistry into bundle sheath (BS) and mesophyll (M) cells, and photorespiration in C plants is predicted to have hydrogen isotopic consequences for metabolites at both molecular and site-specific levels. Molecular-level evidence was recently reported (Zhou et al., 2016), but evidence at the site-specific level is still lacking. We propose that such evidence exists in the contrasting H distribution profiles of glucose samples from naturally grown C , C and CAM plants: photorespiration contributes to the relative H enrichment in H and relative H depletion in H & H (the average of the two pro-chiral Hs and in particular H ) in C glucose, while H-enriched C mesophyll cellular (chloroplastic) water most likely contributes to the enrichment at H ; export of (transferable hydrogen atoms of) NADPH from C mesophyll cells to bundle sheath cells (via the malate shuttle) and incorporation of H-relatively unenriched BS cellular water contribute to the relative depletion of H & H respectively; shuttling of triose-phosphates (PGA: phosphoglycerate dand DHAP: dihydroacetone phosphate) between C bundle sheath and mesophyll cells contributes to the relative enrichment in H & H (in particular H ) in C glucose.
[Mh] Termos MeSH primário: Deutério/química
Glucose/química
Plantas/química
[Mh] Termos MeSH secundário: Configuração de Carboidratos
Deutério/metabolismo
Glucose/metabolismo
Células do Mesofilo/metabolismo
Plantas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
AR09D82C7G (Deuterium); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180105
[Lr] Data última revisão:
180105
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE


  3 / 10762 MEDLINE  
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[PMID]:29232406
[Au] Autor:Feng Y
[Ad] Endereço:Shandong Provincial Key Laboratory of Synthetic Biology, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, China.
[Ti] Título:Compatible topologies and parameters for NMR structure determination of carbohydrates by simulated annealing.
[So] Source:PLoS One;12(12):e0189700, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The use of NMR methods to determine the three-dimensional structures of carbohydrates and glycoproteins is still challenging, in part because of the lack of standard protocols. In order to increase the convenience of structure determination, the topology and parameter files for carbohydrates in the program Crystallography & NMR System (CNS) were investigated and new files were developed to be compatible with the standard simulated annealing protocols for proteins and nucleic acids. Recalculating the published structures of protein-carbohydrate complexes and glycosylated proteins demonstrates that the results are comparable to the published structures which employed more complex procedures for structure calculation. Integrating the new carbohydrate parameters into the standard structure calculation protocol will facilitate three-dimensional structural study of carbohydrates and glycosylated proteins by NMR spectroscopy.
[Mh] Termos MeSH primário: Carboidratos/química
Espectroscopia de Ressonância Magnética/métodos
[Mh] Termos MeSH secundário: Configuração de Carboidratos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carbohydrates)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180104
[Lr] Data última revisão:
180104
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171213
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189700


  4 / 10762 MEDLINE  
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[PMID]:28461332
[Au] Autor:Temple MJ; Cuskin F; Baslé A; Hickey N; Speciale G; Williams SJ; Gilbert HJ; Lowe EC
[Ad] Endereço:From the Institute of Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE4 2HH, United Kingdom and.
[Ti] Título:A Bacteroidetes locus dedicated to fungal 1,6-ß-glucan degradation: Unique substrate conformation drives specificity of the key endo-1,6-ß-glucanase.
[So] Source:J Biol Chem;292(25):10639-10650, 2017 06 23.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Glycans are major nutrients available to the human gut microbiota. The are generalist glycan degraders, and this function is mediated largely by polysaccharide utilization loci (PULs). The genomes of several species contain a PUL, PUL , that was predicted to target mixed linked plant 1,3;1,4-ß-glucans. To test this hypothesis we characterized the proteins encoded by this locus in , a member of the human gut microbiota. We show here that PUL does not orchestrate the degradation of a plant polysaccharide but targets a fungal cell wall glycan, 1,6-ß-glucan, which is a growth substrate for the bacterium. The locus is up-regulated by 1,6-ß-glucan and encodes two enzymes, a surface endo-1,6-ß-glucanase, BT3312, and a periplasmic ß-glucosidase that targets primarily 1,6-ß-glucans. The non-catalytic proteins encoded by PUL target 1,6-ß-glucans and comprise a surface glycan-binding protein and a SusD homologue that delivers glycans to the outer membrane transporter. We identified the central role of the endo-1,6-ß-glucanase in 1,6-ß-glucan depolymerization by deleting , which prevented the growth of on 1,6-ß-glucan. The crystal structure of BT3312 in complex with ß-glucosyl-1,6-deoxynojirimycin revealed a TIM barrel catalytic domain that contains a deep substrate-binding cleft tailored to accommodate the hook-like structure adopted by 1,6-ß-glucan. Specificity is driven by the complementarity of the enzyme active site cleft and the conformation of the substrate. We also noted that PUL is syntenic to many PULs from other Bacteroidetes, suggesting that utilization of yeast and fungal cell wall 1,6-ß-glucans is a widespread adaptation within the human microbiota.
[Mh] Termos MeSH primário: Proteínas de Bactérias/química
Bacteroidetes/enzimologia
Polissacarídeos Fúngicos/química
Glicosídeo Hidrolases/química
beta-Glucanas/química
[Mh] Termos MeSH secundário: Proteínas de Bactérias/genética
Bacteroidetes/genética
Configuração de Carboidratos
Cristalografia por Raios X
Loci Gênicos
Glicosídeo Hidrolases/genética
Seres Humanos
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Fungal Polysaccharides); 0 (beta-Glucans); EC 3.2.1.- (Glycoside Hydrolases); EC 3.2.1.75 (endo-1,6-beta-glucanase)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171229
[Lr] Data última revisão:
171229
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.787606


  5 / 10762 MEDLINE  
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[PMID]:28881287
[Au] Autor:Chen Q; Shao X; Ling P; Liu F; Han G; Wang F
[Ad] Endereço:Shandong Academy of Pharmaceutical Science, Shandong Provincial Key Laboratory of Biopharmaceuticals, Engineering Laboratory of Polysaccharide Drugs, National-Local Joint Engineering Laboratory of Polysaccharide Drugs, Jinan 250101, China; School of Pharmaceutical Sciences, Shandong University, Jina
[Ti] Título:Recent advances in polysaccharides for osteoarthritis therapy.
[So] Source:Eur J Med Chem;139:926-935, 2017 Oct 20.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:The polysaccharides used in the treatment of osteoarthritis (OA) mainly include sodium hyaluronate, chondroitin sulfate, chitosan, xanthan gum, Low molecular weight heparin, alginate and other polysaccharides. This review summarizes the recent advances in the chemistry and biological activities of polysaccharides for the treatment of OA.
[Mh] Termos MeSH primário: Osteoartrite/tratamento farmacológico
Polissacarídeos/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Configuração de Carboidratos
Seres Humanos
Polissacarídeos/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Polysaccharides)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170908
[St] Status:MEDLINE


  6 / 10762 MEDLINE  
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[PMID]:28829786
[Au] Autor:Scarpari M; Reverberi M; Parroni A; Scala V; Fanelli C; Pietricola C; Zjalic S; Maresca V; Tafuri A; Ricciardi MR; Licchetta R; Mirabilii S; Sveronis A; Cescutti P; Rizzo R
[Ad] Endereço:Sapienza University, Dept. of Environmental Biology, P.le Aldo Moro 5, Roma, Italy.
[Ti] Título:Tramesan, a novel polysaccharide from Trametes versicolor. Structural characterization and biological effects.
[So] Source:PLoS One;12(8):e0171412, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mushrooms represent a formidable source of bioactive compounds. Some of these may be considered as biological response modifiers; these include compounds with a specific biological function: antibiotics (e.g. plectasin), immune system stimulator (e,g, lentinan), antitumor agents (e.g. krestin, PSK) and hypolipidemic agents (e.g. lovastatin) inter alia. In this study, we focused on the Chinese medicinal mushroom "yun zhi", Trametes versicolor, traditionally used for (cit.) "replenish essence and qi (vital energy)". Previous studies indicated the potential activity of extracts from culture filtrate of asexual mycelia of T. versicolor in controlling the growth and secondary metabolism (e.g. mycotoxins) of plant pathogenic fungi. The quest of active principles produced by T. versicolor, allowed us characterising an exo-polysaccharide released in its culture filtrate and naming it Tramesan. Herein we evaluate the biological activity of Tramesan in different organisms: plants, mammals and plant pathogenic fungi. We suggest that the bioactivity of Tramesan relies mostly on its ability to act as pro antioxidant molecule regardless the biological system on which it was applied.
[Mh] Termos MeSH primário: Polissacarídeos/química
Polissacarídeos/farmacologia
Trametes/química
[Mh] Termos MeSH secundário: Configuração de Carboidratos
Cromatografia em Gel
Espectroscopia de Ressonância Magnética
Espectrometria de Massas por Ionização por Electrospray
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Polysaccharides)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170823
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0171412


  7 / 10762 MEDLINE  
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[PMID]:28816453
[Au] Autor:Turupcu A; Oostenbrink C
[Ad] Endereço:Institute of Molecular Modeling and Simulation, University of Natural Resources and Life Sciences , Muthgasse 18, 1190 Vienna, Austria.
[Ti] Título:Modeling of Oligosaccharides within Glycoproteins from Free-Energy Landscapes.
[So] Source:J Chem Inf Model;57(9):2222-2236, 2017 Sep 25.
[Is] ISSN:1549-960X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In spite of the abundance of glycoproteins in biological processes, relatively little three-dimensional structural data is available for glycan structures. Here, we study the structure and flexibility of the vast majority of mammalian oligosaccharides appearing in N- and O-glycosylated proteins using a bottom up approach. We report the conformational free-energy landscapes of all relevant glycosidic linkages as obtained from local elevation simulations and subsequent umbrella sampling. To the best of our knowledge, this represents the first complete conformational library for the construction of N- and O-glycan structures. Next, we systematically study the effect of neighboring residues, by extensively simulating all relevant trisaccharides and one tetrasaccharide. This allows for an unprecedented comparison of disaccharide linkages in large oligosaccharides. With a small number of exceptions, the conformational preferences in the larger structures are very similar as in the disaccharides. This, finally, allows us to suggest several efficient approaches to construct complete N- and O-glycans on glycoproteins, as exemplified on two relevant examples.
[Mh] Termos MeSH primário: Glicoproteínas/química
Simulação de Dinâmica Molecular
Oligossacarídeos/química
[Mh] Termos MeSH secundário: Configuração de Carboidratos
Sequência de Carboidratos
Termodinâmica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Glycoproteins); 0 (Oligosaccharides)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170818
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jcim.7b00351


  8 / 10762 MEDLINE  
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[PMID]:28729420
[Au] Autor:Yang Q; Zhang R; Cai H; Wang LX
[Ad] Endereço:From the Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742.
[Ti] Título:Revisiting the substrate specificity of mammalian α1,6-fucosyltransferase reveals that it catalyzes core fucosylation of -glycans lacking α1,3-arm GlcNAc.
[So] Source:J Biol Chem;292(36):14796-14803, 2017 Sep 08.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The mammalian α1,6-fucosyltransferase (FUT8) catalyzes the core fucosylation of -glycans in the biosynthesis of glycoproteins. Previously, intensive studies with crude extract or purified enzyme concluded that the attachment of a GlcNAc on the α1,3 mannose arm of -glycan is essential for FUT8-catalyzed core fucosylation. In contrast, we have recently shown that expression of erythropoietin in a GnTI knock-out, FUT8-overexpressing cell line results in the production of fully core-fucosylated glycoforms of the oligomannose substrate Man GlcNAc , suggesting that FUT8 can catalyze core fucosylation of -glycans lacking an α1,3-arm GlcNAc in cells. Here, we revisited the substrate specificity of FUT8 by examining its activity toward an array of selected -glycans, glycopeptides, and glycoproteins. Consistent with previous studies, we found that free -glycans lacking an unmasked α1,3-arm GlcNAc moiety are not FUT8 substrates. However, Man GlcNAc glycan could be efficiently core-fucosylated by FUT8 in an appropriate protein/peptide context, such as with the erythropoietin protein, a V3 polypeptide derived from HIV-1 gp120, or a simple 9-fluorenylmethyl chloroformate-protected Asn moiety. Interestingly, when placed in the V3 polypeptide context, a mature bi-antennary complex-type -glycan also could be core-fucosylated by FUT8, albeit at much lower efficiency than the Man GlcNAc peptide. This study represents the first report of FUT8-catalyzed core fucosylation of -glycans lacking the α1,3-arm GlcNAc moiety. Our results suggest that an appropriate polypeptide context or other adequate structural elements in the acceptor substrate could facilitate the core fucosylation by FUT8.
[Mh] Termos MeSH primário: Acetilglucosamina/deficiência
Biocatálise
Fucosiltransferases/metabolismo
Polissacarídeos/química
Polissacarídeos/metabolismo
[Mh] Termos MeSH secundário: Adipogenia
Configuração de Carboidratos
Glicosilação
Células HEK293
Seres Humanos
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Polysaccharides); EC 2.4.1.- (Fucosyltransferases); EC 2.4.1.68 (Glycoprotein 6-alpha-L-fucosyltransferase); V956696549 (Acetylglucosamine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170929
[Lr] Data última revisão:
170929
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170722
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.804070


  9 / 10762 MEDLINE  
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[PMID]:28698247
[Au] Autor:Fujimoto Z; Suzuki N; Kishine N; Ichinose H; Momma M; Kimura A; Funane K
[Ad] Endereço:Advanced Analysis Center, National Agriculture and Food Research Organization (NARO), 2-1-2 Kannondai, Tsukuba, Ibaraki 305-8602, Japan zui@affrc.go.jp funane@affrc.go.jp.
[Ti] Título:Carbohydrate-binding architecture of the multi-modular α-1,6-glucosyltransferase from sp. 598K, which produces α-1,6-glucosyl-α-glucosaccharides from starch.
[So] Source:Biochem J;474(16):2763-2778, 2017 Aug 07.
[Is] ISSN:1470-8728
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:sp. 598K α-1,6-glucosyltransferase (Ps6TG31A), a member of glycoside hydrolase family 31, catalyzes exo-α-glucohydrolysis and transglucosylation and produces α-1,6-glucosyl-α-glucosaccharides from α-glucan via its disproportionation activity. The crystal structure of Ps6TG31A was determined by an anomalous dispersion method using a terbium derivative. The monomeric Ps6TG31A consisted of one catalytic (ß/α) -barrel domain and six small domains, one on the N-terminal and five on the C-terminal side. The structures of the enzyme complexed with maltohexaose, isomaltohexaose, and acarbose demonstrated that the ligands were observed in the catalytic cleft and the sugar-binding sites of four ß-domains. The catalytic site was structured by a glucose-binding pocket and an aglycon-binding cleft built by two sidewalls. The bound acarbose was located with its non-reducing end pseudosugar docked in the pocket, and the other moieties along one sidewall serving three subsites for the α-1,4-glucan. The bound isomaltooligosaccharide was found on the opposite sidewall, which provided the space for the acceptor molecule to be positioned for attack of the catalytic intermediate covalent complex during transglucosylation. The N-terminal domain recognized the α-1,4-glucan in a surface-binding mode. Two of the five C-terminal domains belong to the carbohydrate-binding modules family 35 and one to family 61. The sugar complex structures indicated that the first family 35 module preferred α-1,6-glucan, whereas the second family 35 module and family 61 module preferred α-1,4-glucan. Ps6TG31A appears to have enhanced transglucosylation activity facilitated by its carbohydrate-binding modules and substrate-binding cleft that positions the substrate and acceptor sugar for the transglucosylation.
[Mh] Termos MeSH primário: Acarbose/metabolismo
Proteínas de Bactérias/metabolismo
Glucosiltransferases/metabolismo
Oligossacarídeos/metabolismo
Paenibacillus/enzimologia
[Mh] Termos MeSH secundário: Acarbose/química
Apoenzimas/química
Apoenzimas/genética
Apoenzimas/metabolismo
Proteínas de Bactérias/química
Proteínas de Bactérias/genética
Sítios de Ligação
Biocatálise
Configuração de Carboidratos
Domínio Catalítico
Cristalização
Cristalografia por Raios X
Dimerização
Glucosiltransferases/química
Glucosiltransferases/genética
Indicadores e Reagentes/química
Ligantes
Oligossacarídeos/química
Conformação Proteica
Domínios e Motivos de Interação entre Proteínas
Proteínas Recombinantes/química
Térbio/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Apoenzymes); 0 (Bacterial Proteins); 0 (Indicators and Reagents); 0 (Ligands); 0 (Oligosaccharides); 0 (Recombinant Proteins); 06SSF7P179 (Terbium); 34620-77-4 (maltohexaose); 6175-02-6 (isomaltohexose); 804HI855F8 (terbium chloride); EC 2.4.1.- (Glucosyltransferases); T58MSI464G (Acarbose)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170713
[St] Status:MEDLINE
[do] DOI:10.1042/BCJ20170152


  10 / 10762 MEDLINE  
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[PMID]:28685935
[Au] Autor:Ohya A; Yamanoi K; Shimojo H; Fujii C; Nakayama J
[Ad] Endereço:Department of Molecular Pathology, Shinshu University Graduate School of Medicine, Matsumoto, Japan.
[Ti] Título:Gastric gland mucin-specific O-glycan expression decreases with tumor progression from precursor lesions to pancreatic cancer.
[So] Source:Cancer Sci;108(9):1897-1902, 2017 Sep.
[Is] ISSN:1349-7006
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Pancreatic cancer is lethal, as it is often detected late. Thus, novel biomarkers of precursor lesions are needed to devise timely therapies. Pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN) are major precursors of pancreatic cancer. In normal gastric mucosa, gastric gland mucin-specific O-glycans are unique in having α1,4-linked N-acetylglucosamine (αGlcNAc) residues attached to MUC6. Recently we reported that αGlcNAc functions as a tumor suppressor for differentiated-type gastric adenocarcinoma (Karasawa et al., J Clin Invest 122, 923, 2012). MUC6 is also expressed in pancreatic neoplasms, including PanIN and IPMN, but the role of αGlcNAc expression in pancreatic neoplasms remains unknown. Here, we analyze expression patterns of αGlcNAc, MUC6 and MUC5AC in pancreatic neoplasms and compare them with progression from PanIN to invasive ductal adenocarcinoma (IDAC) (the PanIN-IDAC sequence; 20 cases) and from IPMN to IPMN with associated invasive carcinoma (IPMNAIC) (the IPMN-IPMNAIC sequence; 20 cases). At both sequences, the frequency of MUC6-positive and αGlcNAc-positive lesions decreased with tumor progression. We then compared expression levels of αGlcNAc and MUC6 at each step of the progression. At the PanIN-IDAC sequence, αGlcNAc expression significantly decreased relative to MUC6 in low-grade PanIN (P = 0.021), high-grade PanIN/intraductal spread of IDAC (P = 0.031) and IDAC (P = 0.013). At the IPMN-IPMNAIC sequence, decreased αGlcNAc expression was also observed in low-grade IPMN exhibiting gastric-type morphology (P = 0.020). These results suggest that decreased expression of αGlcNAc relative to MUC6 occurs early and marks the initiation of tumor progression to pancreatic cancer.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/metabolismo
Carcinoma Ductal Pancreático/metabolismo
Mucosa Gástrica/metabolismo
Mucina-6/metabolismo
Neoplasias Pancreáticas/metabolismo
[Mh] Termos MeSH secundário: Acetilglucosamina/metabolismo
Configuração de Carboidratos
Carcinogênese
Carcinoma Ductal Pancreático/patologia
Progressão da Doença
Glicosilação
Seres Humanos
Mucina-5AC/metabolismo
Neoplasias Pancreáticas/patologia
Lesões Pré-Cancerosas
Processamento de Proteína Pós-Traducional
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (MUC5AC protein, human); 0 (MUC6 protein, human); 0 (Mucin 5AC); 0 (Mucin-6); V956696549 (Acetylglucosamine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170708
[St] Status:MEDLINE
[do] DOI:10.1111/cas.13317



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