Base de dados : MEDLINE
Pesquisa : D12.644.822.468 [Categoria DeCS]
Referências encontradas : 458 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 46 ir para página                         

  1 / 458 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27025878
[Au] Autor:Ceccato L; Chicanne G; Nahoum V; Pons V; Payrastre B; Gaits-Iacovoni F; Viaud J
[Ad] Endereço:INSERM, U1048 and Université Toulouse 3, I2MC, Avenue Jean Poulhès BP84225, 31432 Toulouse Cedex 04, France.
[Ti] Título:PLIF: A rapid, accurate method to detect and quantitatively assess protein-lipid interactions.
[So] Source:Sci Signal;9(421):rs2, 2016 Mar 29.
[Is] ISSN:1937-9145
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Phosphoinositides are a type of cellular phospholipid that regulate signaling in a wide range of cellular and physiological processes through the interaction between their phosphorylated inositol head group and specific domains in various cytosolic proteins. These lipids also influence the activity of transmembrane proteins. Aberrant phosphoinositide signaling is associated with numerous diseases, including cancer, obesity, and diabetes. Thus, identifying phosphoinositide-binding partners and the aspects that define their specificity can direct drug development. However, current methods are costly, time-consuming, or technically challenging and inaccessible to many laboratories. We developed a method called PLIF (for "protein-lipid interaction by fluorescence") that uses fluorescently labeled liposomes and tethered, tagged proteins or peptides to enable fast and reliable determination of protein domain specificity for given phosphoinositides in a membrane environment. We validated PLIF against previously known phosphoinositide-binding partners for various proteins and obtained relative affinity profiles. Moreover, PLIF analysis of the sorting nexin (SNX) family revealed not only that SNXs bound most strongly to phosphatidylinositol 3-phosphate (PtdIns3P or PI3P), which is known from analysis with other methods, but also that they interacted with other phosphoinositides, which had not previously been detected using other techniques. Different phosphoinositide partners, even those with relatively weak binding affinity, could account for the diverse functions of SNXs in vesicular trafficking and protein sorting. Because PLIF is sensitive, semiquantitative, and performed in a high-throughput manner, it may be used to screen for highly specific protein-lipid interaction inhibitors.
[Mh] Termos MeSH primário: Fosfatos de Fosfatidilinositol/química
Nexinas de Proteases/química
Transdução de Sinais
[Mh] Termos MeSH secundário: Animais
Camundongos
Fosfatos de Fosfatidilinositol/metabolismo
Nexinas de Proteases/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Phosphatidylinositol Phosphates); 0 (Protease Nexins); 0 (phosphatidylinositol 3-phosphate)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160331
[St] Status:MEDLINE
[do] DOI:10.1126/scisignal.aad4337


  2 / 458 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:26387594
[Au] Autor:Olbrich H; Cremers C; Loges NT; Werner C; Nielsen KG; Marthin JK; Philipsen M; Wallmeier J; Pennekamp P; Menchen T; Edelbusch C; Dougherty GW; Schwartz O; Thiele H; Altmüller J; Rommelmann F; Omran H
[Ad] Endereço:Department of General Pediatrics, University Children's Hospital Muenster, 48149 Muenster, Germany. Electronic address: heike.olbrich@ukmuenster.de.
[Ti] Título:Loss-of-Function GAS8 Mutations Cause Primary Ciliary Dyskinesia and Disrupt the Nexin-Dynein Regulatory Complex.
[So] Source:Am J Hum Genet;97(4):546-54, 2015 Oct 01.
[Is] ISSN:1537-6605
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Multiciliated epithelial cells protect the upper and lower airways from chronic bacterial infections by moving mucus and debris outward. Congenital disorders of ciliary beating, referred to as primary ciliary dyskinesia (PCD), are characterized by deficient mucociliary clearance and severe, recurrent respiratory infections. Numerous genetic defects, most of which can be detected by transmission electron microscopy (TEM), are so far known to cause different abnormalities of the ciliary axoneme. However, some defects are not regularly discernable by TEM because the ciliary architecture of the axoneme remains preserved. This applies in particular to isolated defects of the nexin links, also known as the nexin-dynein regulatory complex (N-DRC), connecting the peripheral outer microtubular doublets. Immunofluorescence analyses of respiratory cells from PCD-affected individuals detected a N-DRC defect. Genome-wide exome sequence analyses identified recessive loss-of-function mutations in GAS8 encoding DRC4 in three independent PCD-affected families.
[Mh] Termos MeSH primário: Proteínas do Citoesqueleto/genética
Dineínas/antagonistas & inibidores
Síndrome de Kartagener/etiologia
Complexos Multiproteicos/antagonistas & inibidores
Mutação/genética
Proteínas de Neoplasias/genética
Nexinas de Proteases/antagonistas & inibidores
[Mh] Termos MeSH secundário: Adulto
Animais
Western Blotting
Criança
Cílios/fisiologia
Dineínas/genética
Exoma/genética
Feminino
Seres Humanos
Peptídeos e Proteínas de Sinalização Intracelular/fisiologia
Síndrome de Kartagener/patologia
Masculino
Camundongos
Camundongos Knockout
Microscopia Eletrônica de Transmissão
Microscopia de Fluorescência
Complexos Multiproteicos/genética
Mucosa Nasal/citologia
Mucosa Nasal/metabolismo
Óxido Nítrico/análise
Linhagem
Fenótipo
Prognóstico
Nexinas de Proteases/genética
Sistema Respiratório
Adulto Jovem
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cytoskeletal Proteins); 0 (GAS8 protein, human); 0 (Intracellular Signaling Peptides and Proteins); 0 (Lnk protein, mouse); 0 (Multiprotein Complexes); 0 (Neoplasm Proteins); 0 (Protease Nexins); 31C4KY9ESH (Nitric Oxide); EC 3.6.4.2 (Dyneins)
[Em] Mês de entrada:1601
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150922
[St] Status:MEDLINE


  3 / 458 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:24085025
[Au] Autor:Fisher MJ
[Ad] Endereço:From the Departments of Neurology, Anatomy & Neurobiology, and Pathology & Laboratory Medicine, UC Irvine School of Medicine, Irvine, CA.
[Ti] Título:Brain regulation of thrombosis and hemostasis: from theory to practice.
[So] Source:Stroke;44(11):3275-85, 2013 Nov.
[Is] ISSN:1524-4628
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Encéfalo/fisiologia
Hemostasia/fisiologia
Acidente Vascular Cerebral/prevenção & controle
Acidente Vascular Cerebral/terapia
Trombose/complicações
[Mh] Termos MeSH secundário: Animais
Antitrombina III/metabolismo
Coagulação Sanguínea
Encéfalo/fisiopatologia
Hemorragia Cerebral/patologia
Modelos Animais de Doenças
Epoprostenol/metabolismo
Seres Humanos
Microcirculação
Óxido Nítrico/metabolismo
Inibidor 1 de Ativador de Plasminogênio/metabolismo
Nexinas de Proteases/metabolismo
Trombomodulina/metabolismo
Tromboplastina/metabolismo
Ativador de Plasminogênio Tecidual/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; REVIEW
[Nm] Nome de substância:
0 (Plasminogen Activator Inhibitor 1); 0 (Protease Nexins); 0 (Thrombomodulin); 31C4KY9ESH (Nitric Oxide); 9000-94-6 (Antithrombin III); 9035-58-9 (Thromboplastin); DCR9Z582X0 (Epoprostenol); EC 3.4.21.68 (Tissue Plasminogen Activator)
[Em] Mês de entrada:1312
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:131003
[St] Status:MEDLINE
[do] DOI:10.1161/STROKEAHA.113.000736


  4 / 458 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:23569216
[Au] Autor:Yamamoto R; Song K; Yanagisawa HA; Fox L; Yagi T; Wirschell M; Hirono M; Kamiya R; Nicastro D; Sale WS
[Ad] Endereço:Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.
[Ti] Título:The MIA complex is a conserved and novel dynein regulator essential for normal ciliary motility.
[So] Source:J Cell Biol;201(2):263-78, 2013 Apr 15.
[Is] ISSN:1540-8140
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Axonemal dyneins must be precisely regulated and coordinated to produce ordered ciliary/flagellar motility, but how this is achieved is not understood. We analyzed two Chlamydomonas reinhardtii mutants, mia1 and mia2, which display slow swimming and low flagellar beat frequency. We found that the MIA1 and MIA2 genes encode conserved coiled-coil proteins, FAP100 and FAP73, respectively, which form the modifier of inner arms (MIA) complex in flagella. Cryo-electron tomography of mia mutant axonemes revealed that the MIA complex was located immediately distal to the intermediate/light chain complex of I1 dynein and structurally appeared to connect with the nexin-dynein regulatory complex. In axonemes from mutants that lack both the outer dynein arms and the MIA complex, I1 dynein failed to assemble, suggesting physical interactions between these three axonemal complexes and a role for the MIA complex in the stable assembly of I1 dynein. The MIA complex appears to regulate I1 dynein and possibly outer arm dyneins, which are both essential for normal motility.
[Mh] Termos MeSH primário: Movimento Celular
Chlamydomonas reinhardtii/citologia
Cílios/metabolismo
Sequência Conservada
Dineínas/metabolismo
Complexos Multiproteicos/metabolismo
Proteínas de Plantas/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Axonema/metabolismo
Sequência de Bases
Chlamydomonas reinhardtii/genética
Chlamydomonas reinhardtii/metabolismo
Chlamydomonas reinhardtii/ultraestrutura
Cílios/ultraestrutura
Dineínas/química
Genes de Plantas
Microtúbulos/metabolismo
Modelos Biológicos
Modelos Moleculares
Dados de Sequência Molecular
Mutação/genética
Fenótipo
Proteínas de Plantas/química
Proteínas de Plantas/genética
Nexinas de Proteases/metabolismo
Ligação Proteica
Estabilidade Proteica
Transporte Proteico
Sequências Repetitivas de Aminoácidos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Multiprotein Complexes); 0 (Plant Proteins); 0 (Protease Nexins); EC 3.6.4.2 (Dyneins)
[Em] Mês de entrada:1306
[Cu] Atualização por classe:161019
[Lr] Data última revisão:
161019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130410
[St] Status:MEDLINE
[do] DOI:10.1083/jcb.201211048


  5 / 458 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:20805453
[Au] Autor:Bianchini G; Qi Y; Alvarez RH; Iwamoto T; Coutant C; Ibrahim NK; Valero V; Cristofanilli M; Green MC; Radvanyi L; Hatzis C; Hortobagyi GN; Andre F; Gianni L; Symmans WF; Pusztai L
[Ad] Endereço:Department of Breast Medical Oncology, Unit 1354, The University of Texas M. D. Anderson Cancer Center, PO Box 301439, Houston,TX 77230-1439, USA.
[Ti] Título:Molecular anatomy of breast cancer stroma and its prognostic value in estrogen receptor-positive and -negative cancers.
[So] Source:J Clin Oncol;28(28):4316-23, 2010 Oct 01.
[Is] ISSN:1527-7755
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: The purpose of this study was to identify genes enriched in breast cancer stroma, assess the stromal gene expression differences between estrogen receptor (ER) -positive and -negative cancers, and separately determine their prognostic value in these two subtypes of breast cancers. METHODS: We compared gene expression profiles of pairs of fine-needle (stroma-poor) and core-needle (stroma-rich) biopsies from 37 cancers to identify stroma-associated genes. We defined stromal metagenes and tested their prognostic values in 684 node-negative patients who received no systemic adjuvant therapy and 259 tamoxifen-treated patients. RESULTS: We identified 293 probe sets overexpressed in core biopsies; these included five highly coexpressed gene clusters (metagenes) corresponding to immune functions and extracellular matrix components. These genes showed quantitative and qualitative differences between ER-positive and ER-negative cancers. A B-cell/plasma cell metagene showed strong prognostic value in ER-positive highly proliferative cancers, a lesser prognostic value in ER-negative cancers, and no prognostic value in ER-positive cancers with low proliferation. The hazard ratio for distant relapse in the lowest compared with the highest tertile of the pooled prognostic data set was 4.29 (95% CI, 2.04 to 9.01; P = .001) in ER-positive cancers and 3.34 (95% CI, 1.60 to 6.97; P = .001) in ER-negative cancers. This remained significant in multivariate analysis including routine variables and other genomic prognostic scores. As a result of quantitative differences in this metagene between ER-positive and ER-negative cancers, different thresholds apply in the two subgroups. Other stromal metagenes had inconsistent prognostic value. CONCLUSION: Among ER-negative and ER-positive highly proliferative cancers, a subset of tumors with high expression of a B-cell/plasma cell metagene carries a favorable prognosis.
[Mh] Termos MeSH primário: Neoplasias da Mama/genética
Receptores Estrogênicos/genética
[Mh] Termos MeSH secundário: Precursor de Proteína beta-Amiloide/genética
Antineoplásicos Hormonais/uso terapêutico
Linfócitos B/patologia
Biópsia por Agulha Fina
Neoplasias da Mama/tratamento farmacológico
Neoplasias da Mama/patologia
Distribuição de Qui-Quadrado
Colágeno Tipo IV/genética
Proteínas da Matriz Extracelular
Feminino
Perfilação da Expressão Gênica
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Metagenoma/genética
Recidiva Local de Neoplasia
Proteínas de Transferência de Fosfolipídeos/genética
Prognóstico
Modelos de Riscos Proporcionais
Estudos Prospectivos
Nexinas de Proteases
Proteínas Serina-Treonina Quinases/genética
Receptores de Superfície Celular/genética
Receptores de Fatores de Crescimento Transformadores beta/genética
Análise de Sobrevida
Tamoxifeno/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Amyloid beta-Protein Precursor); 0 (Antineoplastic Agents, Hormonal); 0 (COL4A2 protein, human); 0 (Collagen Type IV); 0 (ECM1 protein, human); 0 (Extracellular Matrix Proteins); 0 (PLTP protein, human); 0 (Phospholipid Transfer Proteins); 0 (Protease Nexins); 0 (Receptors, Cell Surface); 0 (Receptors, Estrogen); 0 (Receptors, Transforming Growth Factor beta); 094ZI81Y45 (Tamoxifen); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); EC 2.7.11.30 (transforming growth factor-beta type II receptor)
[Em] Mês de entrada:1011
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:100901
[St] Status:MEDLINE
[do] DOI:10.1200/JCO.2009.27.2419


  6 / 458 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:20736374
[Au] Autor:Xu D; McKee CM; Cao Y; Ding Y; Kessler BM; Muschel RJ
[Ad] Endereço:Gray Institute of Radiation Oncology and Biology, University of Oxford, Oxford, UK.
[Ti] Título:Matrix metalloproteinase-9 regulates tumor cell invasion through cleavage of protease nexin-1.
[So] Source:Cancer Res;70(17):6988-98, 2010 Sep 01.
[Is] ISSN:1538-7445
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Matrix metalloproteinase-9 (MMP-9) expression is known to enhance the invasion and metastasis of tumor cells. In previous work based on a proteomic screen, we identified the serpin protease nexin-1 (PN-1) as a potential target of MMP-9. Here, we show that PN-1 is a substrate for MMP-9 and establish a link between PN-1 degradation by MMP-9 and regulation of invasion. PN-1 levels increased in prostate carcinoma cells after downregulation of MMP-9 and in tissues of MMP-9-deficient mice, consistent with PN-1 degradation by MMP-9. We identified three MMP-9 cleavage sites in PN-1 and showed that mutations in those sites made PN-1 more resistant to MMP-9. Urokinase plasminogen activator (uPA) is inhibited by PN-1. MMP-9 augmented uPA activity in the medium of PC3-ML cells by degrading PN-1. Prostate cancer cells, overexpressing PN-1 or treated with MMP-9 shRNA, had reduced cell invasion in Matrigel. PN-1 siRNA restored uPA activity and the invasive capacity. PN-1 mutated in the serpin inhibitory domain, the reactive center loop, failed to inhibit uPA and to reduce Matrigel invasion. This study shows a novel molecular pathway in which MMP-9 regulates uPA activity and tumor cell invasion through cleavage of PN-1.
[Mh] Termos MeSH primário: Precursor de Proteína beta-Amiloide/metabolismo
Metaloproteinase 9 da Matriz/metabolismo
Neoplasias da Próstata/enzimologia
Neoplasias da Próstata/patologia
Receptores de Superfície Celular/metabolismo
Serpinas/metabolismo
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Seres Humanos
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Invasividade Neoplásica
Nexinas de Proteases
RNA Interferente Pequeno/genética
Serpina E2
Ativador de Plasminogênio Tipo Uroquinase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Amyloid beta-Protein Precursor); 0 (Protease Nexins); 0 (RNA, Small Interfering); 0 (Receptors, Cell Surface); 0 (SERPINE2 protein, human); 0 (Serpin E2); 0 (Serpine2 protein, mouse); 0 (Serpins); EC 3.4.21.73 (Urokinase-Type Plasminogen Activator); EC 3.4.24.35 (Matrix Metalloproteinase 9)
[Em] Mês de entrada:1010
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:100826
[St] Status:MEDLINE
[do] DOI:10.1158/0008-5472.CAN-10-0242


  7 / 458 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:20720123
[Au] Autor:Fukumoto H; Takahashi H; Tarui N; Matsui J; Tomita T; Hirode M; Sagayama M; Maeda R; Kawamoto M; Hirai K; Terauchi J; Sakura Y; Kakihana M; Kato K; Iwatsubo T; Miyamoto M
[Ad] Endereço:Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Yodogawa-ku, Osaka 532-8686, Japan. Fukumoto_Hiroaki@takeda.co.jp
[Ti] Título:A noncompetitive BACE1 inhibitor TAK-070 ameliorates Abeta pathology and behavioral deficits in a mouse model of Alzheimer's disease.
[So] Source:J Neurosci;30(33):11157-66, 2010 Aug 18.
[Is] ISSN:1529-2401
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We discovered a nonpeptidic compound, TAK-070, that inhibited BACE1, a rate-limiting protease for the generation of Abeta peptides that are considered causative for Alzheimer's disease (AD), in a noncompetitive manner. TAK-070 bound to full-length BACE1, but not to truncated BACE1 lacking the transmembrane domain. Short-term oral administration of TAK-070 decreased the brain levels of soluble Abeta, increased that of neurotrophic sAPPalpha by approximately 20%, and normalized the behavioral impairments in cognitive tests in Tg2576 mice, an APP transgenic mouse model of AD. Six-month chronic treatment decreased cerebral Abeta deposition by approximately 60%, preserving the pharmacological efficacy on soluble Abeta and sAPPalpha levels. These results support the feasibility of BACE1 inhibition with a noncompetitive inhibitor as disease-modifying as well as symptomatic therapy for AD.
[Mh] Termos MeSH primário: Doença de Alzheimer/tratamento farmacológico
Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores
Ácido Aspártico Endopeptidases/antagonistas & inibidores
Compostos de Bifenilo/farmacologia
Encéfalo/efeitos dos fármacos
Transtornos Cognitivos/tratamento farmacológico
Inibidores Enzimáticos/farmacologia
Naftalenos/farmacologia
[Mh] Termos MeSH secundário: Doença de Alzheimer/metabolismo
Doença de Alzheimer/patologia
Secretases da Proteína Precursora do Amiloide/genética
Secretases da Proteína Precursora do Amiloide/metabolismo
Peptídeos beta-Amiloides/metabolismo
Peptídeos beta-Amiloides/secreção
Precursor de Proteína beta-Amiloide/genética
Precursor de Proteína beta-Amiloide/metabolismo
Precursor de Proteína beta-Amiloide/secreção
Animais
Ácido Aspártico Endopeptidases/genética
Ácido Aspártico Endopeptidases/metabolismo
Compostos de Bifenilo/química
Encéfalo/metabolismo
Encéfalo/patologia
Linhagem Celular Tumoral
Transtornos Cognitivos/metabolismo
Transtornos Cognitivos/patologia
Modelos Animais de Doenças
Inibidores Enzimáticos/química
Estudos de Viabilidade
Feminino
Seres Humanos
Masculino
Aprendizagem em Labirinto/efeitos dos fármacos
Camundongos
Camundongos Transgênicos
Naftalenos/química
Nexinas de Proteases
Distribuição Aleatória
Receptores de Superfície Celular/genética
Receptores de Superfície Celular/metabolismo
Recognição (Psicologia)/efeitos dos fármacos
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (APP protein, human); 0 (Amyloid beta-Peptides); 0 (Amyloid beta-Protein Precursor); 0 (Biphenyl Compounds); 0 (Enzyme Inhibitors); 0 (Naphthalenes); 0 (Protease Nexins); 0 (Receptors, Cell Surface); 0 (TAK-070); EC 3.4.- (Amyloid Precursor Protein Secretases); EC 3.4.23.- (Aspartic Acid Endopeptidases); EC 3.4.23.46 (Bace1 protein, mouse)
[Em] Mês de entrada:1009
[Cu] Atualização por classe:101118
[Lr] Data última revisão:
101118
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:100820
[St] Status:MEDLINE
[do] DOI:10.1523/JNEUROSCI.2884-10.2010


  8 / 458 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:20707388
[Au] Autor:Meng F; Abedini A; Plesner A; Verchere CB; Raleigh DP
[Ad] Endereço:Department of Chemistry, State University of New York at Stony Brook, Stony Brook, New York 11794-3400, USA.
[Ti] Título:The flavanol (-)-epigallocatechin 3-gallate inhibits amyloid formation by islet amyloid polypeptide, disaggregates amyloid fibrils, and protects cultured cells against IAPP-induced toxicity.
[So] Source:Biochemistry;49(37):8127-33, 2010 Sep 21.
[Is] ISSN:1520-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Islet amyloid polypeptide (IAPP, amylin) is the major protein component of the islet amyloid deposits associated with type 2 diabetes. The polypeptide lacks a well-defined structure in its monomeric state but readily assembles to form amyloid. Amyloid fibrils formed from IAPP, intermediates generated in the assembly of IAPP amyloid, or both are toxic to ß-cells, suggesting that islet amyloid formation may contribute to the pathology of type 2 diabetes. There are relatively few reported inhibitors of amyloid formation by IAPP. Here we show that the tea-derived flavanol, (-)-epigallocatechin 3-gallate [(2R,3R)-5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-1-benzopyran-3-yl 3,4,5-trihydroxybenzoate] (EGCG), is an effective inhibitor of in vitro IAPP amyloid formation and disaggregates preformed amyloid fibrils derived from IAPP. The compound is thus one of a very small set of molecules which have been shown to disaggregate IAPP amyloid fibrils. Fluorescence-detected thioflavin-T binding assays and transmission electron microscopy confirm that the compound inhibits unseeded amyloid fibril formation as well as disaggregates IAPP amyloid. Seeding studies show that the complex formed by IAPP and EGCG does not seed amyloid formation by IAPP. In this regard, the behavior of IAPP is similar to the reported interactions of Aß and α-synuclein with EGCG. Alamar blue assays and light microscopy indicate that the compound protects cultured rat INS-1 cells against IAPP-induced toxicity. Thus, EGCG offers an interesting lead structure for further development of inhibitors of IAPP amyloid formation and compounds that disaggregate IAPP amyloid.
[Mh] Termos MeSH primário: Amiloide/antagonistas & inibidores
Amiloide/metabolismo
[Mh] Termos MeSH secundário: Amiloide/química
Precursor de Proteína beta-Amiloide
Animais
Catequina/análogos & derivados
Técnicas de Cultura de Células
Diabetes Mellitus Tipo 2/metabolismo
Diabetes Mellitus Tipo 2/patologia
Flavonoides
Polipeptídeo Amiloide das Ilhotas Pancreáticas
Microscopia Eletrônica de Transmissão
Fenóis
Polifenóis
Nexinas de Proteases
Ratos
Receptores de Superfície Celular
Tiazóis
alfa-Sinucleína/análise
alfa-Sinucleína/metabolismo
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Amyloid); 0 (Amyloid beta-Protein Precursor); 0 (Flavonoids); 0 (Islet Amyloid Polypeptide); 0 (Phenols); 0 (Polyphenols); 0 (Protease Nexins); 0 (Receptors, Cell Surface); 0 (Thiazoles); 0 (alpha-Synuclein); 2390-54-7 (thioflavin T); 8R1V1STN48 (Catechin); BQM438CTEL (epigallocatechin gallate)
[Em] Mês de entrada:1010
[Cu] Atualização por classe:161019
[Lr] Data última revisão:
161019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:100817
[St] Status:MEDLINE
[do] DOI:10.1021/bi100939a


  9 / 458 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:20693289
[Au] Autor:Li H; Wang Z; Wang B; Guo Q; Dolios G; Tabuchi K; Hammer RE; Südhof TC; Wang R; Zheng H
[Ad] Endereço:Huffington Center on Aging, Baylor College of Medicine, Houston, Texas 77030, USA.
[Ti] Título:Genetic dissection of the amyloid precursor protein in developmental function and amyloid pathogenesis.
[So] Source:J Biol Chem;285(40):30598-605, 2010 Oct 01.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Proteolytic processing of the amyloid precursor protein (APP) generates large soluble APP derivatives, ß-amyloid (Aß) peptides, and APP intracellular domain. Expression of the extracellular sequences of APP or its Caenorhabditis elegans counterpart has been shown to be sufficient in partially rescuing the CNS phenotypes of the APP-deficient mice and the lethality of the apl-1 null C. elegans, respectively, leaving open the question as what is the role of the highly conserved APP intracellular domain? To address this question, we created an APP knock-in allele in which the mouse Aß sequence was replaced by the human Aß. A frameshift mutation was introduced that replaced the last 39 residues of the APP sequence. We demonstrate that the C-terminal mutation does not overtly affect APP processing and amyloid pathology. In contrast, crossing the mutant allele with APP-like protein 2 (APLP2)-null mice results in similar neuromuscular synapse defects and early postnatal lethality as compared with mice doubly deficient in APP and APLP2, demonstrating an indispensable role of the APP C-terminal domain in these development activities. Our results establish an essential function of the conserved APP intracellular domain in developmental regulation, and this activity can be genetically uncoupled from APP processing and Aß pathogenesis.
[Mh] Termos MeSH primário: Alelos
Doença de Alzheimer/metabolismo
Precursor de Proteína beta-Amiloide/metabolismo
Junção Neuromuscular/metabolismo
Receptores de Superfície Celular/metabolismo
[Mh] Termos MeSH secundário: Doença de Alzheimer/genética
Doença de Alzheimer/patologia
Precursor de Proteína beta-Amiloide/genética
Animais
Caenorhabditis elegans/genética
Caenorhabditis elegans/metabolismo
Proteínas de Caenorhabditis elegans/genética
Proteínas de Caenorhabditis elegans/metabolismo
Modelos Animais de Doenças
Mutação da Fase de Leitura
Técnicas de Introdução de Genes
Seres Humanos
Masculino
Proteínas de Membrana/genética
Proteínas de Membrana/metabolismo
Camundongos
Camundongos Knockout
Junção Neuromuscular/genética
Junção Neuromuscular/patologia
Nexinas de Proteases
Estrutura Terciária de Proteína
Receptores de Superfície Celular/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (APL-1 protein, C elegans); 0 (APP protein, human); 0 (Amyloid beta-Protein Precursor); 0 (Aplp2 protein, mouse); 0 (Caenorhabditis elegans Proteins); 0 (Membrane Proteins); 0 (Protease Nexins); 0 (Receptors, Cell Surface)
[Em] Mês de entrada:1010
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:100810
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M110.137729


  10 / 458 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:20687525
[Au] Autor:Domínguez JL; Christopeit T; Villaverde MC; Gossas T; Otero JM; Nyström S; Baraznenok V; Lindström E; Danielson UH; Sussman F
[Ad] Endereço:Departamento de Química Orgánica, Facultad de Química, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
[Ti] Título:Effect of the protonation state of the titratable residues on the inhibitor affinity to BACE-1.
[So] Source:Biochemistry;49(34):7255-63, 2010 Aug 31.
[Is] ISSN:1520-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACE-1 is one of the aspartic proteases involved in the cleavage of beta amyloid peptide, an initial step in the formation of amyloid plaques whose toxicity induces neuron death in Alzheimer's disease patients. One of the central issues in the search of novel BACE-1 inhibitors is the optimum pH for the binding of inhibitors to the enzyme. It is known that the enzyme has optimal catalytic activity at acidic pH, while cell active inhibitors may bind optimally at higher pH. In this work we determine the effect of the pH on the affinities of a set of inhibitors, with a variety of chemical motifs, for the ectodomain region of BACE-1 by a surface plasmon resonance (SPR) biosensor based assay. In order to understand the molecular interactions that underlie the diverse optimum pH for the binding of the various inhibitors as observed experimentally, we have calculated the titration curves for a set of BACE-1 ligand complexes. The results indicate that the pK(a) values of the titratable residues of the protein depend on the nature of the ligand involved, in disagreement with previous work. The enzyme-inhibitor structures with the resulting protonation states at pH values 4.5 and 7.4 served as the starting point for the prediction of the pH-dependent binding ranking. Our calculations reproduced the entire affinity ranking observed upon pH increase and most of the binding trends among inhibitors, especially at low pH. Finally, our cell-based assays indicate a possible correlation between high inhibitor affinity at both acidic and neutral pH values, with optimal cell response, a result that may open new venues for the search of potent BACE-1 inhibitors that are active at the cellular level.
[Mh] Termos MeSH primário: Inibidores Enzimáticos/química
Fenômenos Físicos
[Mh] Termos MeSH secundário: Precursor de Proteína beta-Amiloide
Inibidores Enzimáticos/farmacologia
Seres Humanos
Ligantes
Nexinas de Proteases
Estrutura Terciária de Proteína
Receptores de Superfície Celular
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., INTRAMURAL
[Nm] Nome de substância:
0 (Amyloid beta-Protein Precursor); 0 (Enzyme Inhibitors); 0 (Ligands); 0 (Protease Nexins); 0 (Receptors, Cell Surface)
[Em] Mês de entrada:1009
[Cu] Atualização por classe:161125
[Lr] Data última revisão:
161125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:100807
[St] Status:MEDLINE
[do] DOI:10.1021/bi100637n



página 1 de 46 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