Base de dados : MEDLINE
Pesquisa : D12.776.395.207 [Categoria DeCS]
Referências encontradas : 1749 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 175 ir para página                         

  1 / 1749 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29324756
[Au] Autor:Haight T; Bryan RN; Meirelles O; Tracy R; Fornage M; Richard M; Nasrallah I; Yaffe K; Jacobs DR; Lewis C; Schreiner P; Sidney S; Davatzikos C; Launer LJ
[Ad] Endereço:Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MD United States of America.
[Ti] Título:Associations of plasma clusterin and Alzheimer's disease-related MRI markers in adults at mid-life: The CARDIA Brain MRI sub-study.
[So] Source:PLoS One;13(1):e0190478, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Clinical and epidemiological studies of older persons have implicated clusterin in Alzheimer's disease (AD) pathogenesis. In the context of identifying early biomarkers of risk, we examined associations of plasma clusterin and characteristics of AD in middle-aged individuals from the community. MATERIALS AND METHODS: Subjects were 639 cognitively normal individuals (mean age 50 ± 3.5) from the Coronary Artery Risk Development in Young Adults (CARDIA) Brain MRI sub-study. Clusterin was quantified using ELISA (mean 255± 31 ng/ml). Associations were assessed between clusterin and volumes of brain regions known to atrophy in early AD, including entorhinal cortex (ECV), hippocampus (HV), and medial temporal lobe (MTLV) volumes (cm3). Total brain volume (TBV) and volumes of structures affected in later AD were examined for comparison. RESULTS: In multivariable models, higher clusterin had a negative non-linear association with ECV (combined left and right hemispheres), and this association was influenced by the highest clusterin levels. Compared to mean clusterin, 1 and 2 standard deviation (SD) level increases in clusterin were associated with -2.1% (95% CI: -3.3,-0.9) and -7.3% (95% CI: -11.3,-3.3) lower ECV, respectively. Similar relationships were observed between clusterin and HV, although the relationship was stronger for left-side HV than the right-side. However, the association was not significant after adjusting for covariates. Negative non-linear associations between clusterin and MTLV were strongest for the left side: compared to mean clusterin, 1 and 2 SD level increases in clusterin were associated with -0.9% (95% CI: -1.9, 0.1) and -3.7% (95% CI: -7.1, -0.3) lower MTLV. There were no significant associations between clusterin and brain structures affected in later AD. CONCLUSIONS: In middle-aged adults unselected for AD, plasma clusterin was associated with lower volume of the entorhinal cortex, an area that atrophies early in AD. Clusterin could be informative as part of a multi-component preclinical marker for AD.
[Mh] Termos MeSH primário: Doença de Alzheimer/sangue
Biomarcadores/sangue
Clusterina/sangue
Imagem por Ressonância Magnética/métodos
[Mh] Termos MeSH secundário: Doença de Alzheimer/diagnóstico por imagem
Doença de Alzheimer/genética
Ensaio de Imunoadsorção Enzimática
Feminino
Seres Humanos
Masculino
Meia-Idade
Polimorfismo de Nucleotídeo Único
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, U.S. GOV'T, P.H.S.
[Nm] Nome de substância:
0 (Biomarkers); 0 (CLU protein, human); 0 (Clusterin)
[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:180112
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190478


  2 / 1749 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29253572
[Au] Autor:Kim YS; Jin HO; Hong SE; Song JY; Hwang CS; Park IC
[Ad] Endereço:Human Resource Biobank, Cheil General Hospital & Women's Healthcare Center, DanKook University College of Medicine, 17, Seoae-ro 1-gil, Jung-gu, Seoul, 04619, Republic of Korea.
[Ti] Título:Silencing of secretory clusterin sensitizes NSCLC cells to V-ATPase inhibitors by downregulating survivin.
[So] Source:Biochem Biophys Res Commun;495(2):2004-2009, 2018 01 08.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Secretory clusterin (sCLU) is a stress-associated protein that confers resistance to therapy when overexpressed. In this study, we observed that the V-ATPase inhibitors bafilomycin A1 and concanamycin A significantly stimulated sCLU protein expression. Knockdown of sCLU with siRNA sensitized non-small cell lung cancer (NSCLC) cells to bafilomycin A1, suggesting that sCLU expression renders cells resistant to V-ATPase inhibitors. The dual PI3K/AKT and mTOR inhibitor BEZ235 suppressed sCLU expression and enhanced cell sensitivity induced by bafilomycin A1. Notably, sCLU knockdown further decreased the expression of the survivin protein by bafilomycin A1, and the ectopic expression of survivin alleviated the cell sensitivity by bafilomycin A1 and sCLU depletion, suggesting that increased sensitivity to sCLU depletion in the cells with V-ATPase inhibitors is due, at least in part, to the down-regulation of survivin. Taken together, we demonstrated that the depletion of sCLU expression enhances the sensitivity of NSCLC cells to V-ATPase inhibitors by decreasing survivin expression. Inhibition of the PI3K/AKT/mTOR pathway enhances the sensitivity of NSCLC cells to V-ATPase inhibitors, leading to decreased sCLU and survivin expression. Thus, we suggest that a combination of PI3K/AKT/mTOR inhibitors with V-ATPase inhibitors might be an effective approach for NSCLC treatment.
[Mh] Termos MeSH primário: Antineoplásicos/administração & dosagem
Carcinoma Pulmonar de Células não Pequenas/terapia
Clusterina/genética
Terapia Genética/métodos
Proteínas Inibidoras de Apoptose/metabolismo
Neoplasias Pulmonares/terapia
ATPases Vacuolares Próton-Translocadoras/antagonistas & inibidores
[Mh] Termos MeSH secundário: Células A549
Apoptose/efeitos dos fármacos
Carcinoma Pulmonar de Células não Pequenas/genética
Carcinoma Pulmonar de Células não Pequenas/patologia
Sobrevivência Celular/efeitos dos fármacos
Terapia Combinada/métodos
Regulação para Baixo/efeitos dos fármacos
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Regulação Neoplásica da Expressão Gênica/genética
Inativação Gênica
Seres Humanos
Neoplasias Pulmonares/genética
Neoplasias Pulmonares/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (BIRC5 protein, human); 0 (CLU protein, human); 0 (Clusterin); 0 (Inhibitor of Apoptosis Proteins); EC 3.6.1.- (Vacuolar Proton-Translocating ATPases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180214
[Lr] Data última revisão:
180214
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171219
[St] Status:MEDLINE


  3 / 1749 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29229391
[Au] Autor:Park JS; Shim YJ; Kang BH; Lee WK; Min BH
[Ad] Endereço:Department of Pharmacology, College of Medicine, Korea University, Seoul, Republic of Korea.
[Ti] Título:Hepatocyte-specific clusterin overexpression attenuates diet-induced nonalcoholic steatohepatitis.
[So] Source:Biochem Biophys Res Commun;495(2):1775-1781, 2018 01 08.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Clusterin is a multifunctional glycoprotein that plays important roles and is up-regulated in liver diseases such as hepatitis and hepatocellular carcinoma. However, little is known about the significance of clusterin in the pathogenesis of non-alcoholic steatohepatitis (NASH). The aim of this study is to examine the role of clusterin in progression of steatohepatitis in mice fed a methionine and choline deficient (MCD) diet. We generated hepatocyte-specific clusterin overexpression (hCLU-tg) mice, and hCLU-tg mice showed lower levels of hepatic triglycerides, less infiltration of macrophages and reduction of TNF-α, activation of Nrf-2 than wild-type littermates fed the MCD diet. Also, sustained clusterin expression in liver ameliorated hepatic fibrogenesis by reducing the activation of hepatic stellate cells by MCD diet. Sustained expression of clusterin in liver functioned as a preconditioning stimulus and prevented MCD diet-induced severe steatohepatitis injury via Nrf2 activation. These results demonstrate a novel function of clusterin as an immune preconditioning regulator in various inflammatory diseases including steatohepatitis.
[Mh] Termos MeSH primário: Clusterina/metabolismo
Hepatócitos/metabolismo
Hepatopatia Gordurosa não Alcoólica/prevenção & controle
[Mh] Termos MeSH secundário: Animais
Deficiência de Colina/complicações
Deficiência de Colina/metabolismo
Clusterina/genética
Dieta/efeitos adversos
Modelos Animais de Doenças
Fígado/metabolismo
Fígado/patologia
Masculino
Metionina/deficiência
Camundongos
Camundongos Transgênicos
Fator 2 Relacionado a NF-E2/metabolismo
Hepatopatia Gordurosa não Alcoólica/etiologia
Hepatopatia Gordurosa não Alcoólica/metabolismo
Estresse Oxidativo
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Clu protein, mouse); 0 (Clusterin); 0 (NF-E2-Related Factor 2); 0 (Nfe2l2 protein, mouse); 0 (RNA, Messenger); AE28F7PNPL (Methionine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171213
[St] Status:MEDLINE


  4 / 1749 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28934225
[Au] Autor:Mackin D; Fave X; Zhang L; Yang J; Jones AK; Ng CS; Court L
[Ad] Endereço:Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States of America.
[Ti] Título:Harmonizing the pixel size in retrospective computed tomography radiomics studies.
[So] Source:PLoS One;12(9):e0178524, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Consistent pixel sizes are of fundamental importance for assessing texture features that relate intensity and spatial information in radiomics studies. To correct for the effects of variable pixel sizes, we combined image resampling with Butterworth filtering in the frequency domain and tested the correction on computed tomography (CT) scans of lung cancer patients reconstructed 5 times with pixel sizes varying from 0.59 to 0.98 mm. One hundred fifty radiomics features were calculated for each preprocessing and field-of-view combination. Intra-patient agreement and inter-patient agreement were compared using the overall concordance correlation coefficient (OCCC). To further evaluate the corrections, hierarchical clustering was used to identify patient scans before and after correction. To assess the general applicability of the corrections, they were applied to 17 CT scans of a radiomics phantom. The reduction in the inter-scanner variability relative to non-small cell lung cancer patient scans was quantified. The variation in pixel sizes caused the intra-patient variability to be large (OCCC <95%) relative to the inter-patient variability in 79% of the features. However, with the resampling and filtering corrections, the intra-patient variability was relatively large in only 10% of the features. With the filtering correction, 8 of 8 patients were correctly clustered, in contrast to only 2 of 8 without the correction. In the phantom study, resampling and filtering the images of a rubber particle cartridge substantially reduced variability in 61% of the radiomics features and substantially increased variability in only 6% of the features. Surprisingly, resampling without filtering tended to increase the variability. In conclusion, applying a correction based on resampling and Butterworth low-pass filtering in the frequency domain effectively reduced variability in CT radiomics features caused by variations in pixel size. This correction may also reduce the variability introduced by other CT scan acquisition parameters.
[Mh] Termos MeSH primário: Processamento de Imagem Assistida por Computador/métodos
Tomografia Computadorizada por Raios X
[Mh] Termos MeSH secundário: Artefatos
Clusterina
Seres Humanos
Estudos Retrospectivos
Razão Sinal-Ruído
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Clusterin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171018
[Lr] Data última revisão:
171018
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170922
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0178524


  5 / 1749 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28902909
[Au] Autor:Vange P; Bruland T; Doseth B; Fossmark R; Sousa MML; Beisvag V; Sørdal Ø; Qvigstad G; Waldum HL; Sandvik AK; Bakke I
[Ad] Endereço:Department of Clinical and Molecular Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
[Ti] Título:The cytoprotective protein clusterin is overexpressed in hypergastrinemic rodent models of oxyntic preneoplasia and promotes gastric cancer cell survival.
[So] Source:PLoS One;12(9):e0184514, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The cytoprotective protein clusterin is often dysregulated during tumorigenesis, and in the stomach, upregulation of clusterin marks emergence of the oxyntic atrophy (loss of acid-producing parietal cells)-associated spasmolytic polypeptide-expressing metaplasia (SPEM). The hormone gastrin is important for normal function and maturation of the gastric oxyntic mucosa and hypergastrinemia might be involved in gastric carcinogenesis. Gastrin induces expression of clusterin in adenocarcinoma cells. In the present study, we examined the expression patterns and gastrin-mediated regulation of clusterin in gastric tissue from: humans; rats treated with proton pump (H+/K+-ATPase) inhibitors and/or a gastrin receptor (CCK2R) antagonist; H+/K+-ATPase ß-subunit knockout (H/K-ß KO) mice; and Mongolian gerbils infected with Helicobacter pylori and given a CCK2R antagonist. Biological function of secretory clusterin was studied in human gastric cancer cells. Clusterin was highly expressed in neuroendocrine cells in normal oxyntic mucosa of humans and rodents. In response to hypergastrinemia, expression of clusterin increased significantly and its localization shifted to basal groups of proliferative cells in the mucous neck cell-chief cell lineage in all animal models. That shift was partially inhibited by antagonizing the CCK2R in rats and gerbils. The oxyntic mucosa of H/K-ß KO mice contained areas with clusterin-positive mucous cells resembling SPEM. In gastric adenocarcinomas, clusterin mRNA expression was higher in diffuse tumors containing signet ring cells compared with diffuse tumors without signet ring cells, and clusterin seemed to be secreted by tumor cells. In gastric cancer cell lines, gastrin increased secretion of clusterin, and both gastrin and secretory clusterin promoted survival after starvation- and chemotherapy-induced stress. Overall, our results indicate that clusterin is overexpressed in hypergastrinemic rodent models of oxyntic preneoplasia and stimulates gastric cancer cell survival.
[Mh] Termos MeSH primário: Clusterina/fisiologia
Regulação Neoplásica da Expressão Gênica
Células Parietais Gástricas/patologia
Neoplasias Gástricas/patologia
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Animais
Carcinogênese/genética
Carcinogênese/metabolismo
Linhagem Celular Tumoral
Clusterina/genética
Clusterina/metabolismo
Feminino
Gastrinas/metabolismo
Gastrinas/fisiologia
Perfilação da Expressão Gênica
Gerbillinae
Seres Humanos
Masculino
Camundongos Knockout
Meia-Idade
Células Parietais Gástricas/metabolismo
Inibidores da Bomba de Prótons/farmacologia
Ratos
Ratos Sprague-Dawley
Receptor de Colecistocinina B/antagonistas & inibidores
Neoplasias Gástricas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Clusterin); 0 (Gastrins); 0 (Proton Pump Inhibitors); 0 (Receptor, Cholecystokinin B)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170914
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184514


  6 / 1749 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28784314
[Au] Autor:Wang Y; Jia Y; Yan L; Fu J; Hao M; Chen W; Yao B; Zhao P; Zhou Z
[Ad] Endereço:Department of Toxicology, School of Public Health, Peking University Health Science Center, Beijing 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, School of Public Health, Peking University Health Science Center, Beijing 100191, PR China.
[Ti] Título:Clusterin and neuropilin-2 as potential biomarkers of tumor progression in benzo[a]pyrene-transformed 16HBE cells xenografted nude mouse model.
[So] Source:Chem Biol Interact;275:145-151, 2017 Sep 25.
[Is] ISSN:1872-7786
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Benzo[a]pyrene (BaP) is a ubiquitous environment contaminant and its exposure could increase incidence of human lung cancer. In order to confirm and compare potential biomarkers of BaP-induce carcinogenesis and tumor progression, time-dependent changes of clusterin (CLU) and neuropilin-2 (NRP2) levels were evaluated in sera of BaP-transformed 16HBE cell line T-16HBE-C1 cells xenografted nude mice. Performance of CLU and NRP2 on tissue classification and tumor progression forecast was also calculated. Levels of CLU and NRP2 were significant elevated in both culture supernatant of T-16HBE-C1 cells and sera of T-16HBE-C1 cells xenografted nude mice compared with control. CLU and NRP2 were both found positively stained in tumor tissue. CLU and NRP2 alone could well predicate tumor progression in nude mice and CLU appeared to be more sensitive than NRP2. When both of them combined, performance of predication would improve. In conclusion, CLU and NRP2 could serve as potential biomarkers of tumor progression in nude mice xenografted with T-16HBE-C1 cells.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/sangue
Transformação Celular Neoplásica
Clusterina/sangue
Neoplasias/fisiopatologia
Neuropilina-2/sangue
[Mh] Termos MeSH secundário: Animais
Área Sob a Curva
Benzo(a)pireno/toxicidade
Biomarcadores Tumorais/análise
Carcinógenos/toxicidade
Linhagem Celular
Clusterina/análise
Progressão da Doença
Seres Humanos
Imuno-Histoquímica
Modelos Lineares
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Nus
Neuropilina-2/análise
Curva ROC
Transplante Heterólogo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (Carcinogens); 0 (Clusterin); 0 (Neuropilin-2); 3417WMA06D (Benzo(a)pyrene)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170809
[St] Status:MEDLINE


  7 / 1749 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28767729
[Au] Autor:Vargas A; Kim HS; Baral E; Yu WQ; Craft CM; Lee EJ
[Ad] Endereço:Mary D. Allen Laboratory for Vision Research, USC Roski Eye Institute, Department of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, California, United States of America.
[Ti] Título:Protective effect of clusterin on rod photoreceptor in rat model of retinitis pigmentosa.
[So] Source:PLoS One;12(8):e0182389, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Retinitis Pigmentosa (RP) begins with the death of rod photoreceptors and is slowly followed by a gradual loss of cones and a rearrangement of the remaining retinal neurons. Clusterin is a chaperone protein that protects cells and is involved in various pathophysiological stresses, including retinal degeneration. Using a well-established transgenic rat model of RP (rhodopsin S334ter), we investigated the effects of clusterin on rod photoreceptor survival. To investigate the role of clusterin in S334ter-line3 retinas, Voronoi analysis and immunohistochemistry were used to evaluate the geometry of rod distribution. Additionally, immunoblot analysis, Bax activation, STAT3 and Akt phosphorylation were used to evaluate the pathway involved in rod cell protection. In this study, clusterin (10µg/ml) intravitreal treatment produced robust preservation of rod photoreceptors in S334ter-line3 retina. The mean number of rods in 1mm2 was significantly greater in clusterin injected RP retinas (postnatal (P) 30, P45, P60, & P75) than in age-matched saline injected RP retinas (P<0.01). Clusterin activated Akt, STAT3 and significantly reduced Bax activity; in addition to inducing phosphorylated STAT3 in Müller cells, which suggests it may indirectly acts on photoreceptors. Thus, clusterin treatment may interferes with mechanisms leading to rod death by suppressing cell death through activation of Akt and STAT3, followed by Bax suppression. Novel insights into the pathway of how clusterin promotes the rod cell survival suggest this treatment may be a potential therapeutic strategy to slow progression of vision loss in human RP.
[Mh] Termos MeSH primário: Clusterina/administração & dosagem
Proteínas Proto-Oncogênicas c-akt/metabolismo
Células Fotorreceptoras Retinianas Bastonetes/efeitos dos fármacos
Retinite Pigmentosa/tratamento farmacológico
Fator de Transcrição STAT3/metabolismo
Proteína X Associada a bcl-2/metabolismo
[Mh] Termos MeSH secundário: Animais
Sobrevivência Celular/efeitos dos fármacos
Clusterina/farmacologia
Modelos Animais de Doenças
Regulação da Expressão Gênica/efeitos dos fármacos
Seres Humanos
Injeções Intravítreas
Fosforilação
Ratos
Células Fotorreceptoras Retinianas Bastonetes/patologia
Retinite Pigmentosa/genética
Transdução de Sinais/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bax protein, rat); 0 (Clusterin); 0 (STAT3 Transcription Factor); 0 (Stat3 protein, rat); 0 (bcl-2-Associated X Protein); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
[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:170803
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0182389


  8 / 1749 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28710283
[Au] Autor:Constantinescu P; Brown RA; Wyatt AR; Ranson M; Wilson MR
[Ti] Título:Amorphous protein aggregates stimulate plasminogen activation, leading to release of cytotoxic fragments that are clients for extracellular chaperones.
[So] Source:J Biol Chem;292(35):14425-14437, 2017 Sep 01.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The misfolding of proteins and their accumulation in extracellular tissue compartments as insoluble amyloid or amorphous protein aggregates are a hallmark feature of many debilitating protein deposition diseases such as Alzheimer's disease, prion diseases, and type II diabetes. The plasminogen activation system is best known as an extracellular fibrinolytic system but was previously reported to also be capable of degrading amyloid fibrils. Here we show that amorphous protein aggregates interact with tissue-type plasminogen activator and plasminogen, via an exposed lysine-dependent mechanism, to efficiently generate plasmin. The insoluble aggregate-bound plasmin is shielded from inhibition by α -antiplasmin and degrades amorphous protein aggregates to release smaller, soluble but relatively hydrophobic fragments of protein (plasmin-generated protein fragments (PGPFs)) that are cytotoxic. , both endothelial and microglial cells bound and internalized PGPFs before trafficking them to lysosomes. Clusterin and α -macroglobulin bound to PGPFs to significantly ameliorate their toxicity. On the basis of these findings, we hypothesize that, as part of the extracellular proteostasis system, the plasminogen activation system may work synergistically with extracellular chaperones to safely clear large and otherwise pathological protein aggregates from the body.
[Mh] Termos MeSH primário: Fibrinolisina/metabolismo
Microglia/efeitos dos fármacos
Fragmentos de Peptídeos/toxicidade
Ativadores de Plasminogênio/toxicidade
Agregados Proteicos
Ativador de Plasminogênio Tecidual/metabolismo
alfa 2-Antiplasmina/metabolismo
[Mh] Termos MeSH secundário: Substituição de Aminoácidos
Animais
Linhagem Celular
Sobrevivência Celular/efeitos dos fármacos
Clusterina/química
Clusterina/metabolismo
Conalbumina/química
Conalbumina/metabolismo
Endotélio Vascular/efeitos dos fármacos
Endotélio Vascular/metabolismo
Endotélio Vascular/patologia
Endotélio Vascular/ultraestrutura
Fibrinolisina/antagonistas & inibidores
Fibrinolisina/química
Seres Humanos
Interações Hidrofóbicas e Hidrofílicas
Camundongos
Microglia/metabolismo
Microglia/patologia
Microglia/ultraestrutura
Mutação
Fragmentos de Peptídeos/química
Fragmentos de Peptídeos/genética
Fragmentos de Peptídeos/metabolismo
Plasminogênio/química
Plasminogênio/metabolismo
Ativadores de Plasminogênio/química
Ativadores de Plasminogênio/genética
Ativadores de Plasminogênio/metabolismo
Proteínas Recombinantes/química
Proteínas Recombinantes/metabolismo
Solubilidade
Superóxido Dismutase-1/química
Superóxido Dismutase-1/genética
Superóxido Dismutase-1/metabolismo
Ativador de Plasminogênio Tecidual/química
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CLU protein, human); 0 (Clusterin); 0 (Peptide Fragments); 0 (Protein Aggregates); 0 (Recombinant Proteins); 0 (SERPINF2 protein, human); 0 (SOD1 protein, human); 0 (alpha-2-Antiplasmin); 1391-06-6 (Conalbumin); 9001-91-6 (Plasminogen); EC 1.15.1.1 (Superoxide Dismutase-1); EC 3.4.21.- (Plasminogen Activators); EC 3.4.21.68 (PLAT protein, human); EC 3.4.21.68 (Tissue Plasminogen Activator); EC 3.4.21.7 (Fibrinolysin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170716
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.786657


  9 / 1749 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28671679
[Au] Autor:Fliegert R; Bauche A; Wolf Pérez AM; Watt JM; Rozewitz MD; Winzer R; Janus M; Gu F; Rosche A; Harneit A; Flato M; Moreau C; Kirchberger T; Wolters V; Potter BVL; Guse AH
[Ad] Endereço:The Calcium Signalling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
[Ti] Título:2'-Deoxyadenosine 5'-diphosphoribose is an endogenous TRPM2 superagonist.
[So] Source:Nat Chem Biol;13(9):1036-1044, 2017 Sep.
[Is] ISSN:1552-4469
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Transient receptor potential melastatin 2 (TRPM2) is a ligand-gated Ca -permeable nonselective cation channel. Whereas physiological stimuli, such as chemotactic agents, evoke controlled Ca signals via TRPM2, pathophysiological stimuli such as reactive oxygen species and genotoxic stress result in prolonged TRPM2-mediated Ca entry and, consequently, apoptosis. To date, adenosine 5'-diphosphoribose (ADPR) has been assumed to be the main agonist for TRPM2. Here we show that 2'-deoxy-ADPR was a significantly better TRPM2 agonist, inducing 10.4-fold higher whole-cell currents at saturation. Mechanistically, this increased activity was caused by a decreased rate of inactivation and higher average open probability. Using high-performance liquid chromatography (HPLC) and mass spectrometry, we detected endogenous 2'-deoxy-ADPR in Jurkat T lymphocytes. Consistently, cytosolic nicotinamide mononucleotide adenylyltransferase 2 (NMNAT-2) and nicotinamide adenine dinucleotide (NAD)-glycohydrolase CD38 sequentially catalyzed the synthesis of 2'-deoxy-ADPR from nicotinamide mononucleotide (NMN) and 2'-deoxy-ATP in vitro. Thus, 2'-deoxy-ADPR is an endogenous TRPM2 superagonist that may act as a cell signaling molecule.
[Mh] Termos MeSH primário: Adenosina Difosfato Ribose/análogos & derivados
Clusterina/agonistas
[Mh] Termos MeSH secundário: ADP-Ribosil Ciclase 1/química
Adenosina Difosfato Ribose/química
Adenosina Difosfato Ribose/farmacologia
Cromatografia Líquida de Alta Pressão
Seres Humanos
Peróxido de Hidrogênio/química
Células Jurkat
Estrutura Molecular
Transdução de Sinais/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (2'-deoxyadenosine diphosphate ribose); 0 (Clusterin); 20762-30-5 (Adenosine Diphosphate Ribose); BBX060AN9V (Hydrogen Peroxide); EC 3.2.2.6 (ADP-ribosyl Cyclase 1)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170704
[St] Status:MEDLINE
[do] DOI:10.1038/nchembio.2415


  10 / 1749 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28532624
[Au] Autor:Yamamoto S; Toda T; Yonezawa R; Negoro T; Shimizu S
[Ad] Endereço:Division of Pharmacology, Faculty of Pharmaceutical Sciences, Teikyo Heisei University, Tokyo, 164-8530, Japan.
[Ti] Título:Tyrphostin AG-related compounds attenuate H O -induced TRPM2-dependent and -independent cellular responses.
[So] Source:J Pharmacol Sci;134(1):68-74, 2017 May.
[Is] ISSN:1347-8648
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:PURPOSE: TRPM2 is a Ca -permeable channel that is activated by H O . TRPM2-mediated Ca signaling has been implicated in the aggravation of inflammatory diseases. Therefore, the development of TRPM2 inhibitors to prevent the aggravation of these diseases is expected. We recently reported that some Tyrphostin AG-related compounds inhibited the H O -induced activation of TRPM2 by scavenging the intracellular hydroxyl radical. In the present study, we examined the effects of AG-related compounds on H O -induced cellular responses in human monocytic U937 cells, which functionally express TRPM2. METHODS: The effects of AG-related compounds on H O -induced changes in intracellular Ca concentrations, extracellular signal-regulated kinase (ERK) activation, and CXCL8 secretion were assessed using U937 cells. RESULTS: Ca influxes via TRPM2 in response to H O were blocked by AG-related compounds. AG-related compounds also inhibited the H O -induced activation of ERK, and subsequent secretion of CXCL8 mediated by TRPM2-dependent and -independent mechanisms. CONCLUSION: Our results show that AG-related compounds inhibit H O -induced CXCL8 secretion following ERK activation, which is mediated by TRPM2-dependent and -independent mechanisms in U937 cells. We previously reported that AG-related compounds blocked H O -induced TRPM2 activation by scavenging the hydroxyl radical. The inhibitory effects of AG-related compounds on TRPM2-independent responses may be due to scavenging of the hydroxyl radical.
[Mh] Termos MeSH primário: Clusterina/metabolismo
Peróxido de Hidrogênio/farmacologia
Interleucina-8/metabolismo
Canais de Cátion TRPM/metabolismo
Tirfostinas/farmacologia
[Mh] Termos MeSH secundário: Cálcio/metabolismo
Ativação Enzimática
MAP Quinases Reguladas por Sinal Extracelular/metabolismo
Seres Humanos
Peróxido de Hidrogênio/metabolismo
L-Lactato Desidrogenase/metabolismo
Estresse Oxidativo
Canais de Cátion TRPM/química
Tirfostinas/química
Células U937
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Clusterin); 0 (IL8 protein, human); 0 (Interleukin-8); 0 (TRPM Cation Channels); 0 (Tyrphostins); BBX060AN9V (Hydrogen Peroxide); EC 1.1.1.27 (L-Lactate Dehydrogenase); EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170713
[Lr] Data última revisão:
170713
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170524
[St] Status:MEDLINE



página 1 de 175 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