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  1 / 1999 MEDLINE  
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[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 / 1999 MEDLINE  
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[PMID]:28455615
[Au] Autor:Meng S; Wu H; Wang L; Zhang B; Bai L
[Ad] Endereço:State Key Laboratory of Microbial Metabolism and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China.
[Ti] Título:Enhancement of antibiotic productions by engineered nitrate utilization in actinomycetes.
[So] Source:Appl Microbiol Biotechnol;101(13):5341-5352, 2017 Jul.
[Is] ISSN:1432-0614
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Nitrate is necessary for primary and secondary metabolism of actinomycetes and stimulates the production of a few antibiotics, such as lincomycin and rifamycin. However, the mechanism of this nitrate-stimulating effect was not fully understood. Two putative ABC-type nitrate transporters were identified in Streptomyces lincolnensis NRRL2936 and verified to be involved in lincomycin biosynthesis. With nitrate supplementation, the transcription of nitrogen assimilation genes, nitrate-specific ABC1 transporter genes, and lincomycin exporter gene lmrA was found to be enhanced and positively regulated by the global regulator GlnR, whose expression was also improved. Moreover, heterologous expression of ABC2 transporter genes in Streptomyces coelicolor M145 resulted in an increased actinorhodin production. Further incorporation of a nitrite-specific transporter gene nirC, as in nirC-ABC2 cassette, led to an even higher actinorhodin production. Similarly, the titers of salinomycin, ansamitocin, lincomycin, and geldanamycin were increased with the integration of this cassette to Streptomyces albus BK3-25, Actinosynnema pretiosum ATCC31280, S. lincolnensis LC-G, and Streptomyces hygroscopicus XM201, respectively. Our work expanded the nitrate-stimulating effect to many antibiotic producers by utilizing the nirC-ABC2 cassette for enhanced nitrate utilization, which could become a general tool for titer increase of antibiotics in actinomycetes.
[Mh] Termos MeSH primário: Actinobacteria/genética
Antibacterianos/biossíntese
Lincomicina/biossíntese
Nitratos/metabolismo
Streptomyces/genética
[Mh] Termos MeSH secundário: Actinobacteria/metabolismo
Proteínas de Transporte de Ânions/genética
Antraquinonas/metabolismo
Antibacterianos/metabolismo
Proteínas de Bactérias/genética
Regulação Bacteriana da Expressão Gênica
Nitrogênio/metabolismo
Piranos/metabolismo
Streptomyces/metabolismo
Streptomyces coelicolor/genética
Transativadores/genética
Transativadores/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anion Transport Proteins); 0 (Anthraquinones); 0 (Anti-Bacterial Agents); 0 (Bacterial Proteins); 0 (GlnR protein, Streptomyces coelicolor); 0 (NirC protein, Bacteria); 0 (Nitrates); 0 (Pyrans); 0 (Trans-Activators); 62UXS86T64 (salinomycin); BOD072YW0F (Lincomycin); G4HH387T6Z (actinorhodin); N762921K75 (Nitrogen)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180104
[Lr] Data última revisão:
180104
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE
[do] DOI:10.1007/s00253-017-8292-7


  3 / 1999 MEDLINE  
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[PMID]:28543431
[Au] Autor:Wang M; Chai N; Sha B; Guo M; Zhuang J; Xu F; Li F
[Ad] Endereço:The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, P. R. China.
[Ti] Título:The effect of substrate stiffness on cancer cell volume homeostasis.
[So] Source:J Cell Physiol;233(2):1414-1423, 2018 Feb.
[Is] ISSN:1097-4652
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Existing studies on the mechanism of cell volume regulation are mainly relevant to ion channels and osmosis in extracellular fluid. Recently, accumulating evidence has shown that cellular mechanical microenvironment also influences the cell volume. Herein, we investigated the regulation of substrate stiffness on the cell volume homeostasis of MCF-7 cells and their following migration behaviors. We found that cell volume increases with increasing substrate stiffness, which could be affected by blocking the cell membrane anion permeability and dopamine receptor. In addition, the cell migration is significantly inhibited by decreasing the cell volume using tamoxifen and such inhibition effect on migration is enhanced by increasing substrate stiffness. The cell membrane anion permeability might be the linker between cellular mechanical microenvironment and cellular volume homeostasis regulation. This work revealed the regulation of substrate stiffness on cell volume homeostasis for the first time, which would provide a new perspective into the understanding of cancer metastasis and a promising anti-cancer therapy through regulation of cell volume homeostasis.
[Mh] Termos MeSH primário: Resinas Acrílicas/química
Neoplasias da Mama/metabolismo
Membrana Celular/metabolismo
Tamanho Celular
Osmorregulação
[Mh] Termos MeSH secundário: Ácido 4,4'-Di-Isotiocianoestilbeno-2,2'-Dissulfônico/farmacologia
Proteínas de Transporte de Ânions/antagonistas & inibidores
Proteínas de Transporte de Ânions/metabolismo
Antineoplásicos Hormonais/farmacologia
Benzazepinas/farmacologia
Neoplasias da Mama/tratamento farmacológico
Neoplasias da Mama/patologia
Adesão Celular
Membrana Celular/efeitos dos fármacos
Membrana Celular/patologia
Permeabilidade da Membrana Celular
Movimento Celular
Tamanho Celular/efeitos dos fármacos
Colágeno/metabolismo
Feminino
Seres Humanos
Hidrogéis
Soluções Hipotônicas/farmacologia
Células MCF-7
Osmorregulação/efeitos dos fármacos
Porosidade
Receptores de Dopamina D1/antagonistas & inibidores
Receptores de Dopamina D1/metabolismo
Tamoxifeno/farmacologia
Microambiente Tumoral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acrylic Resins); 0 (Anion Transport Proteins); 0 (Antineoplastic Agents, Hormonal); 0 (Benzazepines); 0 (DRD1 protein, human); 0 (Hydrogels); 0 (Hypotonic Solutions); 0 (Receptors, Dopamine D1); 0 (SCH 23390); 094ZI81Y45 (Tamoxifen); 9003-05-8 (polyacrylamide); 9007-34-5 (Collagen); Q1O6DSW23R (4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171128
[Lr] Data última revisão:
171128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170526
[St] Status:MEDLINE
[do] DOI:10.1002/jcp.26026


  4 / 1999 MEDLINE  
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[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


  5 / 1999 MEDLINE  
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[PMID]:28812582
[Au] Autor:Schell JC; Wisidagama DR; Bensard C; Zhao H; Wei P; Tanner J; Flores A; Mohlman J; Sorensen LK; Earl CS; Olson KA; Miao R; Waller TC; Delker D; Kanth P; Jiang L; DeBerardinis RJ; Bronner MP; Li DY; Cox JE; Christofk HR; Lowry WE; Thummel CS; Rutter J
[Ad] Endereço:Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA.
[Ti] Título:Control of intestinal stem cell function and proliferation by mitochondrial pyruvate metabolism.
[So] Source:Nat Cell Biol;19(9):1027-1036, 2017 Sep.
[Is] ISSN:1476-4679
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Most differentiated cells convert glucose to pyruvate in the cytosol through glycolysis, followed by pyruvate oxidation in the mitochondria. These processes are linked by the mitochondrial pyruvate carrier (MPC), which is required for efficient mitochondrial pyruvate uptake. In contrast, proliferative cells, including many cancer and stem cells, perform glycolysis robustly but limit fractional mitochondrial pyruvate oxidation. We sought to understand the role this transition from glycolysis to pyruvate oxidation plays in stem cell maintenance and differentiation. Loss of the MPC in Lgr5-EGFP-positive stem cells, or treatment of intestinal organoids with an MPC inhibitor, increases proliferation and expands the stem cell compartment. Similarly, genetic deletion of the MPC in Drosophila intestinal stem cells also increases proliferation, whereas MPC overexpression suppresses stem cell proliferation. These data demonstrate that limiting mitochondrial pyruvate metabolism is necessary and sufficient to maintain the proliferation of intestinal stem cells.
[Mh] Termos MeSH primário: Proliferação Celular
Drosophila melanogaster/metabolismo
Glicólise
Intestinos/metabolismo
Mitocôndrias/metabolismo
Ácido Pirúvico/metabolismo
Células-Tronco/metabolismo
[Mh] Termos MeSH secundário: Acrilatos/farmacologia
Animais
Proteínas de Transporte de Ânions/antagonistas & inibidores
Proteínas de Transporte de Ânions/genética
Proteínas de Transporte de Ânions/metabolismo
Diferenciação Celular
Proliferação Celular/efeitos dos fármacos
Células Cultivadas
Proteínas de Drosophila/genética
Proteínas de Drosophila/metabolismo
Drosophila melanogaster/citologia
Genótipo
Seres Humanos
Intestinos/citologia
Intestinos/efeitos dos fármacos
Ácido Láctico/metabolismo
Camundongos Knockout
Mitocôndrias/efeitos dos fármacos
Proteínas de Transporte da Membrana Mitocondrial/antagonistas & inibidores
Proteínas de Transporte da Membrana Mitocondrial/genética
Proteínas de Transporte da Membrana Mitocondrial/metabolismo
Proteínas Mitocondriais/metabolismo
Fenótipo
Interferência de RNA
Receptores Acoplados a Proteínas-G/genética
Receptores Acoplados a Proteínas-G/metabolismo
Transdução de Sinais
Células-Tronco/efeitos dos fármacos
Fatores de Tempo
Técnicas de Cultura de Tecidos
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acrylates); 0 (Anion Transport Proteins); 0 (Drosophila Proteins); 0 (Lgr5 protein, mouse); 0 (MPC1 protein, Drosophila); 0 (MPC1 protein, human); 0 (MPC1 pyruvate carrier protein, mouse); 0 (Mitochondrial Membrane Transport Proteins); 0 (Mitochondrial Proteins); 0 (Receptors, G-Protein-Coupled); 33X04XA5AT (Lactic Acid); 56396-35-1 (2-cyano-3-(1-phenylindol-3-yl)acrylate); 8558G7RUTR (Pyruvic Acid)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171004
[Lr] Data última revisão:
171004
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170817
[St] Status:MEDLINE
[do] DOI:10.1038/ncb3593


  6 / 1999 MEDLINE  
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[PMID]:28812580
[Au] Autor:Flores A; Schell J; Krall AS; Jelinek D; Miranda M; Grigorian M; Braas D; White AC; Zhou JL; Graham NA; Graeber T; Seth P; Evseenko D; Coller HA; Rutter J; Christofk HR; Lowry WE
[Ad] Endereço:Department of Molecular Cell and Developmental Biology, UCLA, 90095, USA.
[Ti] Título:Lactate dehydrogenase activity drives hair follicle stem cell activation.
[So] Source:Nat Cell Biol;19(9):1017-1026, 2017 Sep.
[Is] ISSN:1476-4679
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Although normally dormant, hair follicle stem cells (HFSCs) quickly become activated to divide during a new hair cycle. The quiescence of HFSCs is known to be regulated by a number of intrinsic and extrinsic mechanisms. Here we provide several lines of evidence to demonstrate that HFSCs utilize glycolytic metabolism and produce significantly more lactate than other cells in the epidermis. Furthermore, lactate generation appears to be critical for the activation of HFSCs as deletion of lactate dehydrogenase (Ldha) prevented their activation. Conversely, genetically promoting lactate production in HFSCs through mitochondrial pyruvate carrier 1 (Mpc1) deletion accelerated their activation and the hair cycle. Finally, we identify small molecules that increase lactate production by stimulating Myc levels or inhibiting Mpc1 carrier activity and can topically induce the hair cycle. These data suggest that HFSCs maintain a metabolic state that allows them to remain dormant and yet quickly respond to appropriate proliferative stimuli.
[Mh] Termos MeSH primário: Proliferação Celular
Senescência Celular
Glicólise
Folículo Piloso/enzimologia
L-Lactato Desidrogenase/metabolismo
Ácido Láctico/metabolismo
Células-Tronco/enzimologia
[Mh] Termos MeSH secundário: Acrilatos/farmacologia
Animais
Proteínas de Transporte de Ânions/antagonistas & inibidores
Proteínas de Transporte de Ânions/genética
Proteínas de Transporte de Ânions/metabolismo
Proliferação Celular/efeitos dos fármacos
Senescência Celular/efeitos dos fármacos
Feminino
Genótipo
Glicólise/efeitos dos fármacos
Folículo Piloso/citologia
Folículo Piloso/efeitos dos fármacos
Isoenzimas/deficiência
Isoenzimas/genética
Isoenzimas/metabolismo
L-Lactato Desidrogenase/deficiência
L-Lactato Desidrogenase/genética
Masculino
Camundongos Endogâmicos C57BL
Camundongos Knockout
Proteínas de Transporte da Membrana Mitocondrial/antagonistas & inibidores
Proteínas de Transporte da Membrana Mitocondrial/genética
Proteínas de Transporte da Membrana Mitocondrial/metabolismo
Fenótipo
Proteínas Proto-Oncogênicas c-myc/metabolismo
Transdução de Sinais
Células-Tronco/efeitos dos fármacos
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acrylates); 0 (Anion Transport Proteins); 0 (Isoenzymes); 0 (MPC1 pyruvate carrier protein, mouse); 0 (Mitochondrial Membrane Transport Proteins); 0 (Myc protein, mouse); 0 (Proto-Oncogene Proteins c-myc); 33X04XA5AT (Lactic Acid); 56396-35-1 (2-cyano-3-(1-phenylindol-3-yl)acrylate); EC 1.1.1.27 (L-Lactate Dehydrogenase); EC 1.1.1.27.- (lactate dehydrogenase 5)
[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:170817
[St] Status:MEDLINE
[do] DOI:10.1038/ncb3575


  7 / 1999 MEDLINE  
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[PMID]:28738416
[Au] Autor:Zhang W; Ogando DG; Kim ET; Choi MJ; Li H; Tenessen JM; Bonanno JA
[Ad] Endereço:School of Optometry, Indiana University, Bloomington, Indiana, United States.
[Ti] Título:Conditionally Immortal Slc4a11-/- Mouse Corneal Endothelial Cell Line Recapitulates Disrupted Glutaminolysis Seen in Slc4a11-/- Mouse Model.
[So] Source:Invest Ophthalmol Vis Sci;58(9):3723-3731, 2017 Jul 01.
[Is] ISSN:1552-5783
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Purpose: To establish conditionally immortal mouse corneal endothelial cell lines with genetically matched Slc4a11+/+ and Slc4a11-/- mice as a model for investigating pathology and therapies for SLC4A11 associated congenital hereditary endothelial dystrophy (CHED) and Fuchs' endothelial corneal dystrophy. Methods: We intercrossed H-2Kb-tsA58 mice (Immortomouse) expressing an IFN-γ dependent and temperature-sensitive mutant of the SV40 large T antigen (tsTAg) with Slc4a11+/+ and Slc4a11-/- C57BL/6 mice. The growth characteristics of the cell lines was assessed by doubling time. Ion transport activities (Na+/H+ exchange, bicarbonate, lactate, and Slc4a11 ammonia transport) were analyzed by intracellular pH measurement. The metabolic status of the cell lines was assessed by analyzing TCA cycle intermediates via gas chromatography mass spectrometry (GC-MS). Results: The immortalized Slc4a11+/+ and Slc4a11-/- mouse corneal endothelial cells (MCECs) remained proliferative through passage 49 and maintained similar active ion transport activity. As expected, proliferation was temperature sensitive and IFN-γ dependent. Slc4a11-/- MCECs exhibited decreased proliferative capacity, reduced NH3:H+ transport, altered expression of glutaminolysis enzymes similar to the Slc4a11-/- mouse, and reduced proportion of TCA cycle intermediates derived from glutamine with compensatory increases in glucose flux compared with Slc4a11+/+ MCECs. Conclusions: This is the first report of the immortalization of MCECs. Ion transport of the immortalized endothelial cells remains active, except for NH3:H+ transporter activity in Slc4a11-/- MCECs. Furthermore, Slc4a11-/- MCECs recapitulate the glutaminolysis defects observed in Slc4a11-/- mouse corneal endothelium, providing an excellent tool to study the pathogenesis of SLC4A11 mutations associated with corneal endothelial dystrophies and to screen potential therapeutic agents.
[Mh] Termos MeSH primário: Proteínas de Transporte de Ânions/genética
Distrofias Hereditárias da Córnea/metabolismo
Epitélio Posterior/metabolismo
Glutamina/metabolismo
Simportadores/genética
[Mh] Termos MeSH secundário: Animais
Proteínas de Transporte de Ânions/metabolismo
Antígenos Transformantes de Poliomavirus/genética
Western Blotting
Linhagem Celular
Proliferação Celular/fisiologia
Distrofias Hereditárias da Córnea/genética
Distrofias Hereditárias da Córnea/patologia
Modelos Animais de Doenças
Epitélio Posterior/patologia
Feminino
Cromatografia Gasosa-Espectrometria de Massas
Transporte de Íons/fisiologia
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Camundongos Transgênicos
Reação em Cadeia da Polimerase em Tempo Real
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anion Transport Proteins); 0 (Antigens, Polyomavirus Transforming); 0 (Slc4a11 protein, mouse); 0 (Symporters); 0RH81L854J (Glutamine)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170728
[Lr] Data última revisão:
170728
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170725
[St] Status:MEDLINE
[do] DOI:10.1167/iovs.17-21781


  8 / 1999 MEDLINE  
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[PMID]:28679589
[Au] Autor:Toyoki D; Shibata S; Kuribayashi-Okuma E; Xu N; Ishizawa K; Hosoyamada M; Uchida S
[Ad] Endereço:Division of Nephrology, Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan; and.
[Ti] Título:Insulin stimulates uric acid reabsorption via regulating urate transporter 1 and ATP-binding cassette subfamily G member 2.
[So] Source:Am J Physiol Renal Physiol;313(3):F826-F834, 2017 Sep 01.
[Is] ISSN:1522-1466
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Accumulating data indicate that renal uric acid (UA) handling is altered in diabetes and by hypoglycemic agents. In addition, hyperinsulinemia is associated with hyperuricemia and hypouricosuria. However, the underlying mechanisms remain unclear. In this study, we aimed to investigate how diabetes and hypoglycemic agents alter the levels of renal urate transporters. In insulin-depleted diabetic rats with streptozotocin treatment, both UA excretion and fractional excretion of UA were increased, suggesting that tubular handling of UA is altered in this model. In the membrane fraction of the kidney, the expression of urate transporter 1 (URAT1) was significantly decreased, whereas that of ATP-binding cassette subfamily G member 2 (ABCG2) was increased, consistent with the increased renal UA clearance. Administration of insulin to the diabetic rats decreased UA excretion and alleviated UA transporter-level changes, while sodium glucose cotransporter 2 inhibitor (SGLT2i) ipragliflozin did not change renal UA handling in this model. To confirm the contribution of insulin in the regulation of urate transporters, normal rats received insulin and separately, ipragliflozin. Insulin significantly increased URAT1 and decreased ABCG2 levels, resulting in increased UA reabsorption. In contrast, the SGLT2i did not alter URAT1 or ABCG2 levels, although blood glucose levels were similarly reduced. Furthermore, we found that insulin significantly increased endogenous URAT1 levels in the membrane fraction of NRK-52E cells, the kidney epithelial cell line, demonstrating the direct effects of insulin on renal UA transport mechanisms. These results suggest a previously unrecognized mechanism for the anti-uricosuric effects of insulin and provide novel insights into the renal UA handling in the diabetic state.
[Mh] Termos MeSH primário: Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo
Proteínas de Transporte de Ânions/metabolismo
Diabetes Mellitus Experimental/tratamento farmacológico
Diabetes Mellitus Tipo 1/tratamento farmacológico
Hipoglicemiantes/farmacologia
Insulina/farmacologia
Túbulos Renais/efeitos dos fármacos
Reabsorção Renal/efeitos dos fármacos
Ácido Úrico/metabolismo
[Mh] Termos MeSH secundário: Animais
Glicemia/efeitos dos fármacos
Glicemia/metabolismo
Linhagem Celular
Diabetes Mellitus Experimental/induzido quimicamente
Diabetes Mellitus Experimental/metabolismo
Diabetes Mellitus Experimental/fisiopatologia
Diabetes Mellitus Tipo 1/induzido quimicamente
Diabetes Mellitus Tipo 1/metabolismo
Diabetes Mellitus Tipo 1/fisiopatologia
Glucosídeos/farmacologia
Túbulos Renais/metabolismo
Túbulos Renais/fisiopatologia
Masculino
Ratos Sprague-Dawley
Eliminação Renal/efeitos dos fármacos
Transportador 2 de Glucose-Sódio/antagonistas & inibidores
Transportador 2 de Glucose-Sódio/metabolismo
Estreptozocina
Tiofenos/farmacologia
Fatores de Tempo
Ácido Úrico/urina
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ATP Binding Cassette Transporter, Sub-Family G, Member 2); 0 (Abcg2 protein, rat); 0 (Anion Transport Proteins); 0 (Blood Glucose); 0 (Glucosides); 0 (Hypoglycemic Agents); 0 (Insulin); 0 (Sglt2 protein, rat); 0 (Sodium-Glucose Transporter 2); 0 (Thiophenes); 0 (URAT1 protein, rat); 268B43MJ25 (Uric Acid); 3N2N8OOR7X (ipragliflozin); 5W494URQ81 (Streptozocin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170707
[St] Status:MEDLINE
[do] DOI:10.1152/ajprenal.00012.2017


  9 / 1999 MEDLINE  
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[PMID]:28538737
[Au] Autor:Mendoza A; Fang V; Chen C; Serasinghe M; Verma A; Muller J; Chaluvadi VS; Dustin ML; Hla T; Elemento O; Chipuk JE; Schwab SR
[Ad] Endereço:Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York 10016, USA.
[Ti] Título:Lymphatic endothelial S1P promotes mitochondrial function and survival in naive T cells.
[So] Source:Nature;546(7656):158-161, 2017 06 01.
[Is] ISSN:1476-4687
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Effective adaptive immune responses require a large repertoire of naive T cells that migrate throughout the body, rapidly identifying almost any foreign peptide. Because the production of T cells declines with age, naive T cells must be long-lived. However, it remains unclear how naive T cells survive for years while constantly travelling. The chemoattractant sphingosine 1-phosphate (S1P) guides T cell circulation among secondary lymphoid organs, including spleen, lymph nodes and Peyer's patches, where T cells search for antigens. The concentration of S1P is higher in circulatory fluids than in lymphoid organs, and the S1P receptor (S1P R) directs the exit of T cells from the spleen into blood, and from lymph nodes and Peyer's patches into lymph. Here we show that S1P is essential not only for the circulation of naive T cells, but also for their survival. Using transgenic mouse models, we demonstrate that lymphatic endothelial cells support the survival of T cells by secreting S1P via the transporter SPNS2, that this S1P signals through S1P R on T cells, and that the requirement for S1P R is independent of the established role of the receptor in guiding exit from lymph nodes. S1P signalling maintains the mitochondrial content of naive T cells, providing cells with the energy to continue their constant migration. The S1P signalling pathway is being targeted therapeutically to inhibit autoreactive T cell trafficking, and these findings suggest that it may be possible simultaneously to target autoreactive or malignant cell survival.
[Mh] Termos MeSH primário: Células Endoteliais/metabolismo
Tecido Linfoide/citologia
Lisofosfolipídeos/metabolismo
Mitocôndrias/metabolismo
Esfingosina/análogos & derivados
Linfócitos T/citologia
[Mh] Termos MeSH secundário: Animais
Proteínas de Transporte de Ânions/metabolismo
Movimento Celular
Sobrevivência Celular
Feminino
Linfonodos/citologia
Linfonodos/imunologia
Tecido Linfoide/imunologia
Masculino
Camundongos
Camundongos Transgênicos
Nódulos Linfáticos Agregados/citologia
Nódulos Linfáticos Agregados/imunologia
Receptores de Lisoesfingolipídeo/metabolismo
Transdução de Sinais
Esfingosina/metabolismo
Baço/citologia
Baço/imunologia
Linfócitos T/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Anion Transport Proteins); 0 (Lysophospholipids); 0 (Receptors, Lysosphingolipid); 0 (Spns2 protein, mouse); 26993-30-6 (sphingosine 1-phosphate); NGZ37HRE42 (Sphingosine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171124
[Lr] Data última revisão:
171124
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170525
[St] Status:MEDLINE
[do] DOI:10.1038/nature22352


  10 / 1999 MEDLINE  
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[PMID]:28289181
[Au] Autor:Xu N; Hirohama D; Ishizawa K; Chang WX; Shimosawa T; Fujita T; Uchida S; Shibata S
[Ad] Endereço:From the Division of Nephrology, Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan (N.X., K.I., S.U., S.S.); Department of Nephrology, Tianjin First Central Hospital, China (N.X., W.X.C.); and Division of Clinical Epigenetics, Research Center for Advanced Science an
[Ti] Título:Hypokalemia and Pendrin Induction by Aldosterone.
[So] Source:Hypertension;69(5):855-862, 2017 May.
[Is] ISSN:1524-4563
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Aldosterone plays an important role in regulating Na-Cl reabsorption and blood pressure. Epithelial Na channel, Na -Cl cotransporter, and Cl /HCO exchanger pendrin are the major mediators of Na-Cl transport in the aldosterone-sensitive distal nephron. Existing evidence also suggests that plasma K concentration affects renal Na-Cl handling. In this study, we posited that hypokalemia modulates the effects of aldosterone on pendrin in hyperaldosteronism. Chronic aldosterone infusion in mice increased pendrin levels at the plasma membrane, and correcting hypokalemia in this model almost completely blocked pendrin upregulation. However, hypokalemia induced by a low-K diet resulted in pendrin downregulation along with reduced plasma aldosterone levels, indicating that both hypokalemia and aldosterone excess are necessary for pendrin induction. In contrast, decreased plasma K levels were sufficient to increase Na -Cl cotransporter levels. We found that phosphorylation of mineralocorticoid receptor that prevents aldosterone binding in intercalated cells was suppressed by hypokalemia, which resulted in enhanced pendrin response to aldosterone, explaining the coordinated action of aldosterone and hypokalemia in pendrin regulation. Finally, to address the physiological significance of our observations, we administered aldosterone to mice lacking pendrin. Notably, plasma K levels were significantly lower in pendrin knockout mice (2.7±0.1 mmol/L) than in wild-type mice (3.0±0.1 mmol/L) after aldosterone infusion, demonstrating that pendrin alleviates hypokalemia in a state of aldosterone excess. These data indicate that the decreased plasma K levels promote pendrin induction by aldosterone, which, in concert with Na -Cl cotransporter, counteracts the progression of hypokalemia but promotes hypertension in primary aldosterone excess.
[Mh] Termos MeSH primário: Aldosterona/farmacologia
Proteínas de Transporte de Ânions/metabolismo
Pressão Sanguínea/fisiologia
Hipopotassemia/metabolismo
Rim/metabolismo
[Mh] Termos MeSH secundário: Aldosterona/sangue
Animais
Proteínas de Transporte de Ânions/genética
Pressão Sanguínea/efeitos dos fármacos
Membrana Celular/efeitos dos fármacos
Membrana Celular/metabolismo
Dieta
Regulação para Baixo/efeitos dos fármacos
Hipertensão/metabolismo
Hipopotassemia/genética
Rim/efeitos dos fármacos
Camundongos
Camundongos Knockout
Fosforilação/efeitos dos fármacos
Receptores de Mineralocorticoides/metabolismo
Simportadores de Cloreto de Sódio/genética
Simportadores de Cloreto de Sódio/metabolismo
Regulação para Cima/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anion Transport Proteins); 0 (Receptors, Mineralocorticoid); 0 (Slc26a4 protein, mouse); 0 (Sodium Chloride Symporters); 4964P6T9RB (Aldosterone)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170428
[Lr] Data última revisão:
170428
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170315
[St] Status:MEDLINE
[do] DOI:10.1161/HYPERTENSIONAHA.116.08519



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