Base de dados : MEDLINE
Pesquisa : G03.143.310 [Categoria DeCS]
Referências encontradas : 30324 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 3033 ir para página                         

  1 / 30324 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29031613
[Au] Autor:Majd H; King MS; Smith AC; Kunji ERS
[Ad] Endereço:Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.
[Ti] Título:Pathogenic mutations of the human mitochondrial citrate carrier SLC25A1 lead to impaired citrate export required for lipid, dolichol, ubiquinone and sterol synthesis.
[So] Source:Biochim Biophys Acta;1859(1):1-7, 2018 01.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Missense mutations of the human mitochondrial citrate carrier, encoded by the SLC25A1 gene, lead to an autosomal recessive neurometabolic disorder characterised by neonatal-onset encephalopathy with severe muscular weakness, intractable seizures, respiratory distress, and lack of psychomotor development, often resulting in early death. Here, we have measured the effect of all twelve known pathogenic mutations on the transport activity. The results show that nine mutations abolish transport of citrate completely, whereas the other three reduce the transport rate by >70%, indicating that impaired citrate transport is the most likely primary cause of the disease. Some mutations may be detrimental to the structure of the carrier, whereas others may impair key functional elements, such as the substrate binding site and the salt bridge network on the matrix side of the carrier. To understand the consequences of impaired citrate transport on metabolism, the substrate specificity was also determined, showing that the human citrate carrier predominantly transports citrate, isocitrate, cis-aconitate, phosphoenolpyruvate and malate. Although D-2- and L-2 hydroxyglutaric aciduria is a metabolic hallmark of the disease, it is unlikely that the citrate carrier plays a significant role in the removal of hydroxyglutarate from the cytosol for oxidation to oxoglutarate in the mitochondrial matrix. In contrast, computer simulations of central metabolism predict that the export of citrate from the mitochondrion cannot be fully compensated by other pathways, restricting the cytosolic production of acetyl-CoA that is required for the synthesis of lipids, sterols, dolichols and ubiquinone, which in turn explains the severe disease phenotypes.
[Mh] Termos MeSH primário: Proteínas de Transporte de Ânions
Ácido Cítrico/metabolismo
Simulação por Computador
Dolicol
Proteínas Mitocondriais
Modelos Biológicos
Mutação de Sentido Incorreto
Esteróis
Ubiquinona
[Mh] Termos MeSH secundário: Proteínas de Transporte de Ânions/química
Proteínas de Transporte de Ânions/genética
Proteínas de Transporte de Ânions/metabolismo
Transporte Biológico Ativo/genética
Encefalopatias Metabólicas Congênitas/enzimologia
Encefalopatias Metabólicas Congênitas/genética
Domínio Catalítico
Dolicol/biossíntese
Dolicol/química
Dolicol/genética
Seres Humanos
Proteínas Mitocondriais/química
Proteínas Mitocondriais/genética
Proteínas Mitocondriais/metabolismo
Esteróis/biossíntese
Esteróis/química
Esteróis/metabolismo
Ubiquinona/biossíntese
Ubiquinona/química
Ubiquinona/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anion Transport Proteins); 0 (Mitochondrial Proteins); 0 (Slc25a1 protein, human); 0 (Sterols); 1339-63-5 (Ubiquinone); 2067-66-5 (Dolichol); 2968PHW8QP (Citric Acid)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171017
[St] Status:MEDLINE


  2 / 30324 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27770219
[Au] Autor:Marshall LE; Koomullil R; Frost AR; Berry JL
[Ad] Endereço:Department of Biomedical Engineering, University of Alabama at Birmingham, Shelby Biomedical Research Bldg. Rm. 802, 1825 University Blvd, Birmingham, AL, 35294, USA.
[Ti] Título:Computational and Experimental Analysis of Fluid Transport Through Three-Dimensional Collagen-Matrigel Hydrogels.
[So] Source:Ann Biomed Eng;45(4):1027-1038, 2017 04.
[Is] ISSN:1573-9686
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A preclinical testing model for cancer therapeutics that replicates in vivo physiology is needed to accurately describe drug delivery and efficacy prior to clinical trials. To develop an in vitro model of breast cancer that mimics in vivo drug/nutrient delivery as well as physiological size and bio-composition, it is essential to describe the mass transport quantitatively. The objective of the present study was to develop in vitro and computational models to measure mass transport from a perfusion system into a 3D extracellular matrix (ECM). A perfusion-flow bioreactor system was used to control and quantify the mass transport of a macromolecule within an ECM hydrogel with embedded through-channels. The material properties, fluid mechanics, and structure of the construct quantified in the in vitro model were input into, and served as validation of, the computational fluid dynamics (CFD) simulation. Results showed that advection and diffusion played a complementary role in mass transport. As the CFD simulation becomes more complex with embedded blood vessels and cancer cells, it will become more recapitulative of in vivo breast cancers. This study is a step toward development of a preclinical testing platform that will be more predictive of patient response to therapeutics than two-dimensional cell culture.
[Mh] Termos MeSH primário: Neoplasias da Mama
Colágeno
Simulação por Computador
Hidrogéis
Laminina
Modelos Biológicos
Neovascularização Patológica
Proteoglicanas
[Mh] Termos MeSH secundário: Transporte Biológico Ativo
Neoplasias da Mama/irrigação sanguínea
Neoplasias da Mama/metabolismo
Neoplasias da Mama/patologia
Combinação de Medicamentos
Feminino
Seres Humanos
Hidrodinâmica
Neovascularização Patológica/metabolismo
Neovascularização Patológica/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Drug Combinations); 0 (Hydrogels); 0 (Laminin); 0 (Proteoglycans); 119978-18-6 (matrigel); 9007-34-5 (Collagen)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161023
[St] Status:MEDLINE
[do] DOI:10.1007/s10439-016-1748-6


  3 / 30324 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28468637
[Au] Autor:Kigen G; Edwards G
[Ad] Endereço:Department of Pharmacology and Toxicology, Moi University School of Medicine, P.O. Box 4606, 30100, Eldoret, Kenya. kigengfk@gmail.com.
[Ti] Título:Drug-transporter mediated interactions between anthelminthic and antiretroviral drugs across the Caco-2 cell monolayers.
[So] Source:BMC Pharmacol Toxicol;18(1):20, 2017 May 04.
[Is] ISSN:2050-6511
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Drug interactions between antiretroviral drugs (ARVs) and anthelminthic drugs, ivermectin (IVM) and praziquantel (PZQ) were assessed by investigating their permeation through the Caco-2 cell monolayers in a transwell. The impact of anthelminthics on the transport of ARVs was determined by assessing the apical to basolateral (AP → BL) [passive] and basolateral to apical (BL → AP) [efflux] directions alone, and in presence of an anthelminthic. The reverse was conducted for the assessment of the influence of ARVs on anthelminthics. METHODS: Samples from the AP and BL compartments were taken at 60, 120, 180 and 240 min and quantified either by HPLC or radiolabeled assay using a liquid scintillating counter for the respective drugs. Transepithelial resistance (TEER) was used to assess the integrity of the monolayers. The amount of compound transported per second (apparent permeability, Papp) was calculated for both AP to BL (Papp ), and BL to AP (Papp ) movements. Samples collected after 60 min were used to determine the efflux ratio (ER), quotient of secretory permeability and absorptive permeability (PappBL-AP/PappAP-BL). The reverse, (PappAP-BL/PappBL-AP) constituted the uptake ratio. The impact of SQV, EFV and NVP on the transport of both IVM and PZQ were investigated. The effect of LPV on the transport of IVM was also determined. The influence of IVM on the transport of SQV, NVP, LPV and EFV; as well as the effect PZQ on the transport of SQV of was also investigated, and a two-tailed p value of <0.05 was considered significant. RESULTS: IVM significantly inhibited the efflux transport (BL → AP movement) of LPV (ER; 6.7 vs. 0.8, p = 0.0038) and SQV (ER; 3.1 vs. 1.2 p = 0.00328); and increased the efflux transport of EFV (ER; 0.7 vs. 0.9, p = 0.031) suggesting the possibility of drug transporter mediated interactions between the two drugs. NVP increased the efflux transport of IVM (ER; 0.8 vs. 1.8, p = 0.0094). CONCLUSIONS: The study provides in vitro evidence of potential interactions between IVM, an anthelminthic drug with antiretroviral drugs; LPV, SQV, NVP and EFV. Further investigations should be conducted to investigate the possibility of in vivo interactions.
[Mh] Termos MeSH primário: Anti-Helmínticos/metabolismo
Antirretrovirais/metabolismo
Ivermectina/metabolismo
Praziquantel/metabolismo
[Mh] Termos MeSH secundário: Transporte Biológico Ativo
Células CACO-2
Interações Medicamentosas
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anthelmintics); 0 (Anti-Retroviral Agents); 6490C9U457 (Praziquantel); 70288-86-7 (Ivermectin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1186/s40360-017-0129-6


  4 / 30324 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29293497
[Au] Autor:Marín de Mas I; Aguilar E; Zodda E; Balcells C; Marin S; Dallmann G; Thomson TM; Papp B; Cascante M
[Ad] Endereço:Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, Universitat de Barcelona, Barcelona, Spain.
[Ti] Título:Model-driven discovery of long-chain fatty acid metabolic reprogramming in heterogeneous prostate cancer cells.
[So] Source:PLoS Comput Biol;14(1):e1005914, 2018 01.
[Is] ISSN:1553-7358
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Epithelial-mesenchymal-transition promotes intra-tumoral heterogeneity, by enhancing tumor cell invasiveness and promoting drug resistance. We integrated transcriptomic data for two clonal subpopulations from a prostate cancer cell line (PC-3) into a genome-scale metabolic network model to explore their metabolic differences and potential vulnerabilities. In this dual cell model, PC-3/S cells express Epithelial-mesenchymal-transition markers and display high invasiveness and low metastatic potential, while PC-3/M cells present the opposite phenotype and higher proliferative rate. Model-driven analysis and experimental validations unveiled a marked metabolic reprogramming in long-chain fatty acids metabolism. While PC-3/M cells showed an enhanced entry of long-chain fatty acids into the mitochondria, PC-3/S cells used long-chain fatty acids as precursors of eicosanoid metabolism. We suggest that this metabolic reprogramming endows PC-3/M cells with augmented energy metabolism for fast proliferation and PC-3/S cells with increased eicosanoid production impacting angiogenesis, cell adhesion and invasion. PC-3/S metabolism also promotes the accumulation of docosahexaenoic acid, a long-chain fatty acid with antiproliferative effects. The potential therapeutic significance of our model was supported by a differential sensitivity of PC-3/M cells to etomoxir, an inhibitor of long-chain fatty acid transport to the mitochondria.
[Mh] Termos MeSH primário: Ácidos Graxos/metabolismo
Neoplasias da Próstata/metabolismo
[Mh] Termos MeSH secundário: Ácido Araquidônico/metabolismo
Transporte Biológico Ativo/efeitos dos fármacos
Linhagem Celular Tumoral
Proliferação Celular
Biologia Computacional
Ácidos Docosa-Hexaenoicos/metabolismo
Eicosanoides/metabolismo
Transição Epitelial-Mesenquimal
Compostos de Epóxi/farmacologia
Ácidos Graxos/química
Seres Humanos
Masculino
Redes e Vias Metabólicas
Mitocôndrias/metabolismo
Modelos Biológicos
Invasividade Neoplásica
Neoplasias da Próstata/tratamento farmacológico
Neoplasias da Próstata/patologia
Transcriptoma
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Eicosanoids); 0 (Epoxy Compounds); 0 (Fatty Acids); 25167-62-8 (Docosahexaenoic Acids); 27YG812J1I (Arachidonic Acid); MSB3DD2XP6 (etomoxir)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180210
[Lr] Data última revisão:
180210
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180103
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pcbi.1005914


  5 / 30324 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29323106
[Au] Autor:Samanta K; Mirams GR; Parekh AB
[Ad] Endereço:Department of Physiology, Anatomy and Genetics, Oxford University, Parks Road, Oxford, OX1 3PT, UK.
[Ti] Título:Sequential forward and reverse transport of the Na Ca exchanger generates Ca oscillations within mitochondria.
[So] Source:Nat Commun;9(1):156, 2018 01 11.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Mitochondrial Ca homoeostasis regulates aerobic metabolism and cell survival. Ca flux into mitochondria is mediated by the mitochondrial calcium uniporter (MCU) channel whereas Ca export is often through an electrogenic Na -Ca exchanger. Here, we report remarkable functional versatility in mitochondrial Na -Ca exchange under conditions where mitochondria are depolarised. Following physiological stimulation of cell-surface receptors, mitochondrial Na -Ca exchange initially operates in reverse mode, transporting cytosolic Ca into the matrix. As matrix Ca rises, the exchanger reverts to its forward mode state, extruding Ca . Transitions between reverse and forward modes generate repetitive oscillations in matrix Ca . We further show that reverse mode Na -Ca activity is regulated by the mitochondrial fusion protein mitofusin 2. Our results demonstrate that reversible switching between transport modes of an ion exchanger molecule generates functionally relevant oscillations in the levels of the universal Ca messenger within an organelle.
[Mh] Termos MeSH primário: Cálcio/metabolismo
Mitocôndrias/metabolismo
Trocador de Sódio e Cálcio/metabolismo
[Mh] Termos MeSH secundário: Animais
Transporte Biológico Ativo/fisiologia
Linhagem Celular
Seres Humanos
Potencial da Membrana Mitocondrial
Modelos Biológicos
Permeabilidade
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Sodium-Calcium Exchanger); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180202
[Lr] Data última revisão:
180202
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180112
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02638-2


  6 / 30324 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
[PMID]:29215240
[Au] Autor:Poryadin GV; Vlasov AP; Trofimov VA; Vlasova TI; Kamkina OV; Grigoryev AG; Vlasov PA
[Ti] Título:[Hemoglobin oxygen transport capacity in surgical endotoxicosis ].
[So] Source:Patol Fiziol Eksp Ter;60(1):23-7, 2016 Jan-Mar.
[Is] ISSN:0031-2991
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Ab] Resumo:In surgical endointoxication hemoglobin oxygen transport capacity of red blood cells (hemoglobin affinity ligands: the ability to bind and release ligands) is reduced and is associated with the severity of endogenous intoxication. Violation of oxygen transport function of hemoglobin at endogenous intoxication is associated with conformational changes of a biomolecule, and its possible influence on reactive oxygen species, which confirmed in experiments in vitro: under the influence of oxygen-iron ascorbate ability of hemoglobin deteriorates. Largely similar structural and functional changes in hemoglobin occur in patients with surgical endotoxicosis.
[Mh] Termos MeSH primário: Endotoxemia/metabolismo
Eritrócitos/metabolismo
Hemoglobinas/metabolismo
Oxigênio/metabolismo
Complicações Pós-Operatórias/metabolismo
[Mh] Termos MeSH secundário: Adulto
Transporte Biológico Ativo
Endotoxemia/etiologia
Eritrócitos/patologia
Feminino
Seres Humanos
Masculino
Meia-Idade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hemoglobins); S88TT14065 (Oxygen)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171221
[Lr] Data última revisão:
171221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171208
[St] Status:MEDLINE


  7 / 30324 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29054412
[Au] Autor:Duck KA; Simpson IA; Connor JR
[Ad] Endereço:Department of Neurosurgery, Penn State Hershey Medical Center, Hershey, PA, United States.
[Ti] Título:Regulatory mechanisms for iron transport across the blood-brain barrier.
[So] Source:Biochem Biophys Res Commun;494(1-2):70-75, 2017 Dec 09.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Many critical metabolic functions in the brain require adequate and timely delivery of iron. However, most studies when considering brain iron uptake have ignored the iron requirements of the endothelial cells that form the blood-brain barrier (BBB). Moreover, current models of BBB iron transport do not address regional regulation of brain iron uptake or how neurons, when adapting to metabolic demands, can acquire more iron. In this study, we demonstrate that both iron-poor transferrin (apo-Tf) and the iron chelator, deferoxamine, stimulate release of iron from iron-loaded endothelial cells in an in vitro BBB model. The role of the endosomal divalent metal transporter 1 (DMT1) in BBB iron acquisition and transport has been questioned. Here, we show that inhibition of DMT1 alters the transport of iron and Tf across the endothelial cells. These data support an endosome-mediated model of Tf-bound iron uptake into the brain and identifies mechanisms for local regional regulation of brain iron uptake. Moreover, our data provide an explanation for the disparity in the ratio of Tf to iron transport into the brain that has confounded the field.
[Mh] Termos MeSH primário: Barreira Hematoencefálica/metabolismo
Ferro/metabolismo
[Mh] Termos MeSH secundário: Animais
Transporte Biológico Ativo/efeitos dos fármacos
Barreira Hematoencefálica/efeitos dos fármacos
Encéfalo/irrigação sanguínea
Encéfalo/metabolismo
Proteínas de Transporte de Cátions/antagonistas & inibidores
Proteínas de Transporte de Cátions/metabolismo
Bovinos
Células Cultivadas
Endossomos/metabolismo
Células Endoteliais/metabolismo
Hepcidinas/metabolismo
Microvasos/metabolismo
Modelos Neurológicos
Transferrina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cation Transport Proteins); 0 (Hepcidins); 0 (Transferrin); 0 (solute carrier family 11- (proton-coupled divalent metal ion transporters), member 2); E1UOL152H7 (Iron)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171113
[Lr] Data última revisão:
171113
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171022
[St] Status:MEDLINE


  8 / 30324 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29050941
[Au] Autor:Nooron N; Athipornchai A; Suksamrarn A; Chiabchalard A
[Ad] Endereço:Ph.D. program in Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
[Ti] Título:Mahanine enhances the glucose-lowering mechanisms in skeletal muscle and adipocyte cells.
[So] Source:Biochem Biophys Res Commun;494(1-2):101-106, 2017 Dec 09.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Insulin resistance is a major defect underlying type 2 diabetes development. Skeletal muscle tissue and adipocyte tissue are the major sites of postprandial glucose disposal, and enhancing glucose uptake into this tissue may decrease insulin resistance in type 2 diabetes patients. Mahanine (3,11-dihydro-3,5-dimethyl-3-(4-methyl-3-pentenyl)pyrano[3,2-a]carbazol-9-ol) has been reported to be a major bioactive carbazole alkaloid that has many biological activities including antitumor, anti-inflammatory, antioxidant and anti-diabetic activities. However, the molecular mechanism and signaling pathways mediating the anti-diabetic effects of mahanine require further investigation. Therefore, the aim of this study was to investigate the effects of mahanine, a carbazole alkaloid from Murraya koenigii, on glucose uptake and glucose transporter 4 (GLUT4) translocation in skeletal muscle and adipocyte cells. Mahanine treatment promoted a dose dependent increased in glucose uptake in L6 myotubes and adipocyte cells via activation of the Akt signaling pathway. Mahanine induced Akt-activation was reversed by co-treatment with wortmannin, an Akt inhibitor. Moreover, it was found that mahanine significantly enhanced GLUT4 translocation to the plasma membrane in L6 myotubes. These results suggest that increased activation of the Akt signaling pathway lead to increased plasma membrane GLUT4 content and increased glucose uptake. These data strongly suggest that mahanine has anti-diabetic potential for treating diabetes.
[Mh] Termos MeSH primário: Adipócitos/efeitos dos fármacos
Adipócitos/metabolismo
Carbazóis/farmacologia
Glucose/metabolismo
Hipoglicemiantes/farmacologia
Músculo Esquelético/efeitos dos fármacos
Músculo Esquelético/metabolismo
[Mh] Termos MeSH secundário: Células 3T3-L1
Proteínas Quinases Ativadas por AMP/metabolismo
Animais
Transporte Biológico Ativo/efeitos dos fármacos
Carbazóis/administração & dosagem
Linhagem Celular
Membrana Celular/efeitos dos fármacos
Membrana Celular/metabolismo
Sobrevivência Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Transportador de Glucose Tipo 4/metabolismo
Hipoglicemiantes/administração & dosagem
Resistência à Insulina
Camundongos
Fibras Musculares Esqueléticas/efeitos dos fármacos
Fibras Musculares Esqueléticas/metabolismo
Proteínas Proto-Oncogênicas c-akt/metabolismo
Transdução de Sinais/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carbazoles); 0 (Glucose Transporter Type 4); 0 (Hypoglycemic Agents); 0 (Slc2a4 protein, mouse); 0 (mahanine); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); EC 2.7.11.31 (AMP-Activated Protein Kinases); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171021
[St] Status:MEDLINE


  9 / 30324 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28934248
[Au] Autor:Liu W; Tang FL; Lin S; Zhao K; Mei L; Ye J; Xiong WC
[Ad] Endereço:Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, Georgia, United States of America.
[Ti] Título:Vps35-deficiency impairs SLC4A11 trafficking and promotes corneal dystrophy.
[So] Source:PLoS One;12(9):e0184906, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Vps35 (vacuolar protein sorting 35) is a major component of retromer that selectively promotes endosome-to-Golgi retrieval of transmembrane proteins. Dysfunction of retromer is a risk factor for the pathogenesis of Parkinson's disease (PD) and Alzheimer's disease (AD). However, Vps35/retromer's function in the eye or the contribution of Vps35-deficiency to eye degenerative disorders remains to be explored. Here we provide evidence for a critical role of Vps35 in mouse corneal dystrophy. Vps35 is expressed in mouse and human cornea. Mouse cornea from Vps35 heterozygotes (Vps35+/-) show features of dystrophy, such as loss of both endothelial and epithelial cell densities, disorganizations of endothelial, stroma, and epithelial cells, excrescences in the Descemet membrane, and corneal edema. Additionally, corneal epithelial cell proliferation was reduced in Vps35-deficient mice. Intriguingly, cell surface targeting of SLC4A11, a membrane transport protein (OH- /H+ /NH3 /H2O) of corneal endothelium, whose mutations have been identified in patients with corneal dystrophy, was impaired in Vps35-deficient cells and cornea. Taken together, these results suggest that SLC4A11 appears to be a Vps35/retromer cargo, and Vps35-regulation of SLC4A11 trafficking may underlie Vps35/retromer regulation of corneal dystrophy.
[Mh] Termos MeSH primário: Proteínas de Transporte de Ânions/metabolismo
Transporte Biológico Ativo/fisiologia
Córnea/metabolismo
Distrofias Hereditárias da Córnea/metabolismo
Simportadores/metabolismo
Proteínas de Transporte Vesicular/deficiência
[Mh] Termos MeSH secundário: Animais
Western Blotting
Proliferação Celular/fisiologia
Córnea/patologia
Distrofias Hereditárias da Córnea/patologia
Modelos Animais de Doenças
Células Epiteliais/metabolismo
Células Epiteliais/patologia
Imunofluorescência
Células HEK293
Seres Humanos
Camundongos Transgênicos
Microscopia Confocal
Retina/metabolismo
Retina/patologia
Transfecção
Proteínas de Transporte Vesicular/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anion Transport Proteins); 0 (Slc4a11 protein, mouse); 0 (Symporters); 0 (Vesicular Transport Proteins); 0 (Vps35 protein, mouse)
[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:170922
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184906


  10 / 30324 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28883039
[Au] Autor:Huynh W; Vale RD
[Ad] Endereço:Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA.
[Ti] Título:Disease-associated mutations in human BICD2 hyperactivate motility of dynein-dynactin.
[So] Source:J Cell Biol;216(10):3051-3060, 2017 Oct 02.
[Is] ISSN:1540-8140
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Bicaudal D2 (BICD2) joins dynein with dynactin into a ternary complex (termed DDB) capable of processive movement. Point mutations in the gene have been identified in patients with a dominant form of spinal muscular atrophy, but how these mutations cause disease is unknown. To investigate this question, we have developed in vitro motility assays with purified DDB and BICD2's membrane vesicle partner, the GTPase Rab6a. Rab6a-GTP, either in solution or bound to artificial liposomes, released BICD2 from an autoinhibited state and promoted robust dynein-dynactin transport. In these assays, BICD2 mutants showed an enhanced ability to form motile DDB complexes. Increased retrograde transport by BICD2 mutants also was observed in cells using an inducible organelle transport assay. When overexpressed in rat hippocampal neurons, the hyperactive BICD2 mutants decreased neurite growth. Our results reveal that dominant mutations in BICD2 hyperactivate DDB motility and suggest that an imbalance of minus versus plus end-directed microtubule motility in neurons may underlie spinal muscular atrophy.
[Mh] Termos MeSH primário: Complexo Dinactina/metabolismo
Dineínas/metabolismo
Proteínas Associadas aos Microtúbulos/genética
Proteínas Associadas aos Microtúbulos/metabolismo
Mutação Puntual
[Mh] Termos MeSH secundário: Animais
Transporte Biológico Ativo/genética
Linhagem Celular
Complexo Dinactina/genética
Dineínas/genética
Hipocampo/metabolismo
Hipocampo/patologia
Seres Humanos
Camundongos
Complexos Multiproteicos/genética
Complexos Multiproteicos/metabolismo
Atrofia Muscular Espinal/genética
Atrofia Muscular Espinal/metabolismo
Atrofia Muscular Espinal/patologia
Neuritos/metabolismo
Neuritos/patologia
Ratos
Suínos
Proteínas rab de Ligação ao GTP/genética
Proteínas rab de Ligação ao GTP/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (BICD2 protein, human); 0 (Dynactin Complex); 0 (Microtubule-Associated Proteins); 0 (Multiprotein Complexes); 0 (Rab6 protein); EC 3.6.4.2 (Dyneins); EC 3.6.5.2 (rab GTP-Binding Proteins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170909
[St] Status:MEDLINE
[do] DOI:10.1083/jcb.201703201



página 1 de 3033 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