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[PMID]:28731330
[Au] Autor:Colas C; Schlessinger A; Pajor AM
[Ad] Endereço:Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai , New York, New York 10029, United States.
[Ti] Título:Mapping Functionally Important Residues in the Na /Dicarboxylate Cotransporter, NaDC1.
[So] Source:Biochemistry;56(33):4432-4441, 2017 Aug 22.
[Is] ISSN:1520-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Transporters from the SLC13 family couple the transport of two to four Na ions with a di- or tricarboxylate, such as succinate or citrate. We have previously modeled mammalian members of the SLC13 family, including the Na /dicarboxylate cotransporter NaDC1 (SLC13A2), based on a structure of the bacterial homologue VcINDY in an inward-facing conformation with one sodium ion bound at the Na1 site. In the study presented here, we modeled the outward-facing conformation of rabbit and human NaDC1 (rbNaDC1 and hNaDC1, respectively) using an outward-facing model of VcINDY as a template and identified residues in or near the putative Na2 and Na3 cation binding sites. Guided by the structural models in both conformations, we performed site-directed mutagenesis in rbNaDC1 for residues proposed to be in the Na or substrate binding sites. Cysteine substitution of T474 in the predicted Na2 binding site results in an inactive protein. The M539C mutant has a low apparent affinity for both sodium and lithium cations, suggesting that M539 may form part of the putative Na3 binding site. The Y432C and T86C mutants have increased K values for succinate, supporting their proposed location in the outward-facing substrate binding site. In addition, cysteine labeling by MTSEA-biotin shows that Y432C is accessible from the outside of the cell, and the accessibility changes in the presence or absence of Na . The results of this study improve our understanding of substrate and ion recognition in the mammalian members of the SLC13 family and provide a framework for developing conformationally specific inhibitors against these transporters.
[Mh] Termos MeSH primário: Transportadores de Ácidos Dicarboxílicos/química
Lítio/química
Modelos Moleculares
Transportadores de Ânions Orgânicos Dependentes de Sódio/química
Sódio/química
Ácido Succínico/química
Simportadores/química
[Mh] Termos MeSH secundário: Substituição de Aminoácidos
Animais
Sítios de Ligação
Cátions Monovalentes/química
Cátions Monovalentes/metabolismo
Transportadores de Ácidos Dicarboxílicos/genética
Transportadores de Ácidos Dicarboxílicos/metabolismo
Células HEK293
Seres Humanos
Lítio/metabolismo
Mutação de Sentido Incorreto
Transportadores de Ânions Orgânicos Dependentes de Sódio/genética
Transportadores de Ânions Orgânicos Dependentes de Sódio/metabolismo
Mapeamento de Peptídeos
Coelhos
Sódio/metabolismo
Ácido Succínico/metabolismo
Simportadores/genética
Simportadores/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cations, Monovalent); 0 (Dicarboxylic Acid Transporters); 0 (Organic Anion Transporters, Sodium-Dependent); 0 (SLC13A2 protein, human); 0 (Symporters); 9FN79X2M3F (Lithium); 9NEZ333N27 (Sodium); AB6MNQ6J6L (Succinic Acid)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170831
[Lr] Data última revisão:
170831
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170722
[St] Status:MEDLINE
[do] DOI:10.1021/acs.biochem.7b00503


  2 / 372 MEDLINE  
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[PMID]:28662289
[Au] Autor:Lin YY; Yu MW; Lin SM; Lee SD; Chen CL; Chen DS; Chen PJ
[Ad] Endereço:Graduate Institute of Clinical Medicine, National Taiwan University, Taipei, Taiwan.
[Ti] Título:Genome-wide association analysis identifies a GLUL haplotype for familial hepatitis B virus-related hepatocellular carcinoma.
[So] Source:Cancer;123(20):3966-3976, 2017 Oct 15.
[Is] ISSN:1097-0142
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: A family history of liver cancer increases the risk of developing hepatocellular carcinoma (HCC) by 2-fold to 10-fold among patients with chronic hepatitis B virus (HBV). Previous genome-wide association studies have identified many possible susceptible loci associated with sporadic HBV-related HCC. However, despite family history being a well-known risk factor for HBV-related HCC, to the authors' knowledge its genetic mechanisms and associating loci remain largely unknown or unexplored, most likely due to the relative rarity of familial HCC and the difficulty of sample collection. METHODS: The authors conducted a genome-wide association study with 139 male cases with familial HBV-related HCC and 139 non-HCC male controls with chronic HBV. The results were corroborated further with an independent cohort of 101 patients with familial HBV-related HCC and comparison with both the 1000 Genomes Project and the Taiwan Biobank. RESULTS: A total of 51 risk single-nucleotide polymorphisms (P≤1E-04) were identified in the association analyses, which included 2 clusters of associated single-nucleotide polymorphisms and haplotypes at 1q25.3 (glutamate-ammonia ligase [GLUL]/transmembrane epididymal protein 1 [TEDDM1]/long intergenic non-protein-coding RNA 272 [LINC00272]/regulator of G-protein signaling-like 1 [RGSL1]) and 17q11.2 (solute carrier family 13 member 2 [SLC13A2]/forkhead box N1 [FOXN1]). Both the GLUL and SLC13A2/FOXN1 haplotypes have large effect sizes and were found to be different from those found from genome-wide association studies of sporadic HCCs. CONCLUSIONS: To the authors' knowledge, the current study is the first genome-wide association study to identify genetic factors for familial HBV-related HCC. The results identified 2 large effect susceptible haplotypes located at GLUL and SLC13A2/FOXN1. The current study findings also suggest different genetic susceptibility between familial and sporadic HBV-related HCC. Cancer 2017;123:3966-76. © 2017 American Cancer Society.
[Mh] Termos MeSH primário: Carcinoma Hepatocelular/genética
Glutamato-Amônia Ligase/genética
Neoplasias Hepáticas/genética
[Mh] Termos MeSH secundário: Adulto
Idoso
Grupo com Ancestrais do Continente Asiático/genética
Estudos de Casos e Controles
Transportadores de Ácidos Dicarboxílicos/genética
Fatores de Transcrição Forkhead/genética
Predisposição Genética para Doença
Estudo de Associação Genômica Ampla
Genótipo
Haplótipos
Hepatite B Crônica/complicações
Seres Humanos
Masculino
Proteínas de Membrana/genética
Meia-Idade
Transportadores de Ânions Orgânicos Dependentes de Sódio/genética
Polimorfismo de Nucleotídeo Único
Proteínas/genética
RNA Longo não Codificante/genética
Simportadores/genética
Taiwan
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dicarboxylic Acid Transporters); 0 (Forkhead Transcription Factors); 0 (Membrane Proteins); 0 (Organic Anion Transporters, Sodium-Dependent); 0 (Proteins); 0 (RGSL1 protein, human); 0 (RNA, Long Noncoding); 0 (SLC13A2 protein, human); 0 (Symporters); 0 (TEDDM1 protein, human); 0 (Whn protein); EC 6.3.1.2 (Glutamate-Ammonia Ligase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171011
[Lr] Data última revisão:
171011
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170630
[St] Status:MEDLINE
[do] DOI:10.1002/cncr.30851


  3 / 372 MEDLINE  
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[PMID]:28570579
[Au] Autor:Kulyté A; Ehrlund A; Arner P; Dahlman I
[Ad] Endereço:Lipid laboratory, Department of Medicine H7, Karolinska Institutet, Stockholm, Sweden.
[Ti] Título:Global transcriptome profiling identifies KLF15 and SLC25A10 as modifiers of adipocytes insulin sensitivity in obese women.
[So] Source:PLoS One;12(6):e0178485, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Although the mechanisms linking obesity to insulin resistance (IR) and type 2 diabetes (T2D) are not entirely understood, it is likely that alterations of adipose tissue function are involved. The aim of this study was to identify new genes controlling insulin sensitivity in adipocytes from obese women with either insulin resistant (OIR) or sensitive (OIS) adipocytes. Insulin sensitivity was first determined by measuring lipogenesis in isolated adipocytes from abdominal subcutaneous white adipose tissue (WAT) in a large observational study. Lipogenesis was measured under conditions where glucose transport was the rate limiting step and reflects in vivo insulin sensitivity. We then performed microarray-based transcriptome profiling on subcutaneous WAT specimen from a subgroup of 9 lean, 21 OIS and 18 obese OIR women. We could identify 432 genes that were differentially expressed between the OIR and OIS group (FDR ≤5%). These genes are enriched in pathways related to glucose and amino acid metabolism, cellular respiration, and insulin signaling, and include genes such as SLC2A4, AKT2, as well as genes coding for enzymes in the mitochondria respiratory chain. Two IR-associated genes, KLF15 encoding a transcription factor and SLC25A10 encoding a dicarboxylate carrier, were selected for functional evaluation in adipocytes differentiated in vitro. Knockdown of KLF15 and SLC25A10 using siRNA inhibited insulin-stimulated lipogenesis in adipocytes. Transcriptome profiling of siRNA-treated cells suggested that KLF15 might control insulin sensitivity by influencing expression of PPARG, PXMP2, AQP7, LPL and genes in the mitochondrial respiratory chain. Knockdown of SLC25A10 had only modest impact on the transcriptome, suggesting that it might directly influence insulin sensitivity in adipocytes independently of transcription due to its important role in fatty acid synthesis. In summary, this study identifies novel genes associated with insulin sensitivity in adipocytes in women independently of obesity. KFL15 and SLC25A10 are inhibitors of insulin-stimulated lipogenesis under conditions when glucose transport is the rate limiting step.
[Mh] Termos MeSH primário: Adipócitos/metabolismo
Transportadores de Ácidos Dicarboxílicos/genética
Perfilação da Expressão Gênica
Resistência à Insulina
Fatores de Transcrição Kruppel-Like/genética
Obesidade/metabolismo
Transcriptoma
[Mh] Termos MeSH secundário: Adulto
Feminino
Técnicas de Silenciamento de Genes
Seres Humanos
Meia-Idade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dicarboxylic Acid Transporters); 0 (KLF5 protein, human); 0 (Kruppel-Like Transcription Factors); 0 (Slc25a10 protein, human)
[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:170602
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0178485


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[PMID]:28406943
[Au] Autor:Irizarry AR; Yan G; Zeng Q; Lucchesi J; Hamang MJ; Ma YL; Rong JX
[Ad] Endereço:Department of Pathology, Lilly Research Laboratories, Eli Lilly & Company, Indianapolis, IN, United States of America.
[Ti] Título:Defective enamel and bone development in sodium-dependent citrate transporter (NaCT) Slc13a5 deficient mice.
[So] Source:PLoS One;12(4):e0175465, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:There has been growing recognition of the essential roles of citrate in biomechanical properties of mineralized tissues, including teeth and bone. However, the sources of citrate in these tissues have not been well defined, and the contribution of citrate to the regulation of odontogenesis and osteogenesis has not been examined. Here, tooth and bone phenotypes were examined in sodium-dependent citrate transporter (NaCT) Slc13a5 deficient C57BL/6 mice at 13 and 32 weeks of age. Slc13a5 deficiency led to defective tooth development, characterized by absence of mature enamel, formation of aberrant enamel matrix, and dysplasia and hyperplasia of the enamel organ epithelium that progressed with age. These abnormalities were associated with fragile teeth with a possible predisposition to tooth abscesses. The lack of mature enamel was consistent with amelogenesis imperfecta. Furthermore, Slc13a5 deficiency led to decreased bone mineral density and impaired bone formation in 13-week-old mice but not in older mice. The findings revealed the potentially important role of citrate and Slc13a5 in the development and function of teeth and bone.
[Mh] Termos MeSH primário: Densidade Óssea/fisiologia
Ácido Cítrico/metabolismo
Esmalte Dentário/metabolismo
Transportadores de Ácidos Dicarboxílicos/metabolismo
Osteogênese/fisiologia
Simportadores/metabolismo
[Mh] Termos MeSH secundário: Animais
Transportadores de Ácidos Dicarboxílicos/deficiência
Camundongos
Camundongos Knockout
Simportadores/deficiência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dicarboxylic Acid Transporters); 0 (Slc13a5 protein, mouse); 0 (Symporters); 2968PHW8QP (Citric Acid)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170504
[Lr] Data última revisão:
170504
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170414
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0175465


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[PMID]:28288640
[Au] Autor:Yang L; Christakou E; Vang J; Lübeck M; Lübeck PS
[Ad] Endereço:Section for Sustainable Biotechnology, Department of Chemistry and Bioscience, Aalborg University Copenhagen, A. C. Meyers Vænge 15, 2450, Copenhagen SV, Denmark.
[Ti] Título:Overexpression of a C -dicarboxylate transporter is the key for rerouting citric acid to C -dicarboxylic acid production in Aspergillus carbonarius.
[So] Source:Microb Cell Fact;16(1):43, 2017 Mar 14.
[Is] ISSN:1475-2859
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: C -dicarboxylic acids, including malic acid, fumaric acid and succinic acid, are valuable organic acids that can be produced and secreted by a number of microorganisms. Previous studies on organic acid production by Aspergillus carbonarius, which is capable of producing high amounts of citric acid from varieties carbon sources, have revealed its potential as a fungal cell factory. Earlier attempts to reroute citric acid production into C -dicarboxylic acids have been with limited success. RESULTS: In this study, a glucose oxidase deficient strain of A. carbonarius was used as the parental strain to overexpress a native C -dicarboxylate transporter and the gene frd encoding fumarate reductase from Trypanosoma brucei individually and in combination. Impacts of the introduced genetic modifications on organic acid production were investigated in a defined medium and in a hydrolysate of wheat straw containing high concentrations of glucose and xylose. In the defined medium, overexpression of the C -dicarboxylate transporter alone and in combination with the frd gene significantly increased the production of C -dicarboxylic acids and reduced the accumulation of citric acid, whereas expression of the frd gene alone did not result in any significant change of organic acid production profile. In the wheat straw hydrolysate after 9 days of cultivation, similar results were obtained as in the defined medium. High amounts of malic acid and succinic acid were produced by the same strains. CONCLUSIONS: This study demonstrates that the key to change the citric acid production into production of C -dicarboxylic acids in A. carbonarius is the C -dicarboxylate transporter. Furthermore it shows that the C -dicarboxylic acid production by A. carbonarius can be further increased via metabolic engineering and also shows the potential of A. carbonarius to utilize lignocellulosic biomass as substrates for C -dicarboxylic acid production.
[Mh] Termos MeSH primário: Aspergillus/genética
Aspergillus/metabolismo
Ácido Cítrico/metabolismo
Transportadores de Ácidos Dicarboxílicos/genética
Transportadores de Ácidos Dicarboxílicos/metabolismo
Ácidos Dicarboxílicos/metabolismo
Regulação para Cima
[Mh] Termos MeSH secundário: Biomassa
Meios de Cultura/química
Glucose/metabolismo
Glucose Oxidase/genética
Glucose Oxidase/metabolismo
Lignina/metabolismo
Malatos/metabolismo
Engenharia Metabólica/métodos
Polissacarídeos/metabolismo
Succinato Desidrogenase/genética
Triticum/metabolismo
Trypanosoma brucei brucei/enzimologia
Trypanosoma brucei brucei/genética
Xilose/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Culture Media); 0 (Dicarboxylic Acid Transporters); 0 (Dicarboxylic Acids); 0 (Malates); 0 (Polysaccharides); 11132-73-3 (lignocellulose); 2968PHW8QP (Citric Acid); 817L1N4CKP (malic acid); 9005-53-2 (Lignin); A1TA934AKO (Xylose); EC 1.1.3.4 (Glucose Oxidase); EC 1.3.99.1 (Succinate Dehydrogenase); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170420
[Lr] Data última revisão:
170420
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170315
[St] Status:MEDLINE
[do] DOI:10.1186/s12934-017-0660-6


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[PMID]:28258579
[Au] Autor:Huang B; Wang H; Yang B
[Ad] Endereço:Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
[Ti] Título:Water Transport Mediated by Other Membrane Proteins.
[So] Source:Adv Exp Med Biol;969:251-261, 2017.
[Is] ISSN:0065-2598
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Water transport through membrane is so intricate that there are still some debates. (Aquaporins) AQPs are entirely accepted to allow water transmembrane movement depending on osmotic gradient. Cotransporters and uniporters , however, are also concerned in water homeotatsis. Urea transporter B (UT-B) has a single-channel water permeability that is similar to AQP1. Cystic fibrosis transmembrane conductance regulator (CFTR ) was initially thought as a water channel but now not believed to transport water directly. By cotranporters, water is transported by water osmosis coupling with substrates, which explains how water is transported across the isolated small intestine. This chapter provides information about water transport mediated by other membrane proteins except AQPs .
[Mh] Termos MeSH primário: Células Eucarióticas/metabolismo
Transportador 1 de Aminoácido Excitatório/metabolismo
Transportadores de Ácidos Monocarboxílicos/metabolismo
Simportadores/metabolismo
Água/metabolismo
[Mh] Termos MeSH secundário: Animais
Transporte Biológico
Regulador de Condutância Transmembrana em Fibrose Cística/genética
Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo
Transportadores de Ácidos Dicarboxílicos/genética
Transportadores de Ácidos Dicarboxílicos/metabolismo
Células Eucarióticas/citologia
Transportador 1 de Aminoácido Excitatório/genética
Regulação da Expressão Gênica
Seres Humanos
Proteínas de Membrana Transportadoras/genética
Proteínas de Membrana Transportadoras/metabolismo
Transportadores de Ácidos Monocarboxílicos/genética
Transportadores de Ânions Orgânicos Dependentes de Sódio/genética
Transportadores de Ânions Orgânicos Dependentes de Sódio/metabolismo
Concentração Osmolar
Transportador 1 de Glucose-Sódio/genética
Transportador 1 de Glucose-Sódio/metabolismo
Membro 2 da Família 12 de Carreador de Soluto/genética
Membro 2 da Família 12 de Carreador de Soluto/metabolismo
Simportadores/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (CFTR protein, human); 0 (Dicarboxylic Acid Transporters); 0 (Excitatory Amino Acid Transporter 1); 0 (Membrane Transport Proteins); 0 (Monocarboxylic Acid Transporters); 0 (Organic Anion Transporters, Sodium-Dependent); 0 (SLC12A7 protein, human); 0 (SLC13A2 protein, human); 0 (SLC1A3 protein, human); 0 (SLC5A1 protein, human); 0 (Sodium-Glucose Transporter 1); 0 (Solute Carrier Family 12, Member 2); 0 (Symporters); 0 (monocarboxylate transport protein 1); 0 (urea transporter); 059QF0KO0R (Water); 126880-72-6 (Cystic Fibrosis Transmembrane Conductance Regulator)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170305
[St] Status:MEDLINE
[do] DOI:10.1007/978-94-024-1057-0_17


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[PMID]:28025701
[Au] Autor:Unrean P
[Ad] Endereço:National Center for Genetic Engineering and Biotechnology (BIOTEC), 113 Thailand Science Park, Paholyothin Road, Klong 1, Klong Luang, Pathumthani, 12120, Thailand. pornkamol.unr@biotec.or.th.
[Ti] Título:Flux control-based design of furfural-resistance strains of Saccharomyces cerevisiae for lignocellulosic biorefinery.
[So] Source:Bioprocess Biosyst Eng;40(4):611-623, 2017 Apr.
[Is] ISSN:1615-7605
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:We have previously developed a dynamic flux balance analysis of Saccharomyces cerevisiae for elucidation of genome-wide flux response to furfural perturbation (Unrean and Franzen, Biotechnol J 10(8):1248-1258, 2015). Herein, the dynamic flux distributions were analyzed by flux control analysis to identify target overexpressed genes for improved yeast robustness against furfural. The flux control coefficient (FCC) identified overexpressing isocitrate dehydrogenase (IDH1), a rate-controlling flux for ethanol fermentation, and dicarboxylate carrier (DIC1), a limiting flux for cell growth, as keys of furfural-resistance phenotype. Consistent with the model prediction, strain characterization showed 1.2- and 2.0-fold improvement in ethanol synthesis and furfural detoxification rates, respectively, by IDH1 overexpressed mutant compared to the control. DIC1 overexpressed mutant grew at 1.3-fold faster and reduced furfural at 1.4-fold faster than the control under the furfural challenge. This study hence demonstrated the FCC-based approach as an effective tool for guiding the design of robust yeast strains.
[Mh] Termos MeSH primário: Transportadores de Ácidos Dicarboxílicos
Farmacorresistência Fúngica
Furaldeído/farmacologia
Isocitrato Desidrogenase
Lignina/metabolismo
Proteínas de Saccharomyces cerevisiae
Saccharomyces cerevisiae
[Mh] Termos MeSH secundário: Transportadores de Ácidos Dicarboxílicos/genética
Transportadores de Ácidos Dicarboxílicos/metabolismo
Farmacorresistência Fúngica/efeitos dos fármacos
Farmacorresistência Fúngica/genética
Isocitrato Desidrogenase/genética
Isocitrato Desidrogenase/metabolismo
Saccharomyces cerevisiae/genética
Saccharomyces cerevisiae/metabolismo
Proteínas de Saccharomyces cerevisiae/genética
Proteínas de Saccharomyces cerevisiae/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dicarboxylic Acid Transporters); 0 (Saccharomyces cerevisiae Proteins); 11132-73-3 (lignocellulose); 9005-53-2 (Lignin); DJ1HGI319P (Furaldehyde); EC 1.1.1.41 (Isocitrate Dehydrogenase)
[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:161228
[St] Status:MEDLINE
[do] DOI:10.1007/s00449-016-1725-3


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[PMID]:27927654
[Au] Autor:Lee HW; Handlogten ME; Osis G; Clapp WL; Wakefield DN; Verlander JW; Weiner ID
[Ad] Endereço:Division of Nephrology, Hypertension and Renal Transplantation, University of Florida College of Medicine, Gainesville, Florida.
[Ti] Título:Expression of sodium-dependent dicarboxylate transporter 1 (NaDC1/SLC13A2) in normal and neoplastic human kidney.
[So] Source:Am J Physiol Renal Physiol;312(3):F427-F435, 2017 Mar 01.
[Is] ISSN:1522-1466
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Regulated dicarboxylate transport is critical for acid-base homeostasis, prevention of calcium nephrolithiasis, regulation of collecting duct sodium chloride transport, and the regulation of blood pressure. Although luminal dicarboxylate reabsorption via NaDC1 (SLC13A2) is believed to be the primary mechanism regulating renal dicarboxylate transport, the specific localization of NaDC1 in the human kidney is currently unknown. This study's purpose was to determine NaDC1's expression in normal and neoplastic human kidneys. Immunoblot analysis demonstrated NaDC1 expression with an apparent molecular weight of ~61 kDa. Immunohistochemistry showed apical NaDC1 immunolabel in the proximal tubule of normal human kidney tissue; well-preserved proximal tubule brush border was clearly labeled. Apical NaDC1 expression was evident throughout the entire proximal tubule, including the initial proximal convoluted tubule, as identified by origination from the glomerular tuft, and extending through the terminal of the proximal tubule, the proximal straight tubule in the outer medulla. We confirmed proximal tubule localization by colocalization with the proximal tubule specific protein, NBCe1. NaDC1 immunolabel was not detected other than in the proximal tubule. In addition, NaDC1 immunolabel was not detected in tumors of presumed proximal tubule origin, clear cell and papillary renal cell carcinoma, or in tumors of nonproximal tubule origin, oncocytoma and chromophobe carcinoma. In summary, ) in the human kidney, apical NaDC1 immunolabel is present throughout the entire proximal tubule, and is not detectable in other renal cells; and ) NaDC1 immunolabel is not present in renal tumors. These studies provide important information regarding NaDC1's role in human dicarboxylate metabolism.
[Mh] Termos MeSH primário: Transportadores de Ácidos Dicarboxílicos/análise
Neoplasias Renais/química
Túbulos Renais Proximais/química
Transportadores de Ânions Orgânicos Dependentes de Sódio/análise
Simportadores/análise
[Mh] Termos MeSH secundário: Western Blotting
Seres Humanos
Imuno-Histoquímica
Neoplasias Renais/patologia
Túbulos Renais Proximais/patologia
Microvilosidades/química
Peso Molecular
Simportadores de Sódio-Bicarbonato/análise
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dicarboxylic Acid Transporters); 0 (Organic Anion Transporters, Sodium-Dependent); 0 (SLC13A2 protein, human); 0 (SLC4A4 protein, human); 0 (Sodium-Bicarbonate Symporters); 0 (Symporters)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171020
[Lr] Data última revisão:
171020
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161209
[St] Status:MEDLINE
[do] DOI:10.1152/ajprenal.00559.2016


  9 / 372 MEDLINE  
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[PMID]:27812114
[Au] Autor:Lourenço M; Ramiro RS; Güleresi D; Barroso-Batista J; Xavier KB; Gordo I; Sousa A
[Ad] Endereço:Instituto Gulbenkian de Ciência, Oeiras, Portugal.
[Ti] Título:A Mutational Hotspot and Strong Selection Contribute to the Order of Mutations Selected for during Escherichia coli Adaptation to the Gut.
[So] Source:PLoS Genet;12(11):e1006420, 2016 Nov.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The relative role of drift versus selection underlying the evolution of bacterial species within the gut microbiota remains poorly understood. The large sizes of bacterial populations in this environment suggest that even adaptive mutations with weak effects, thought to be the most frequently occurring, could substantially contribute to a rapid pace of evolutionary change in the gut. We followed the emergence of intra-species diversity in a commensal Escherichia coli strain that previously acquired an adaptive mutation with strong effect during one week of colonization of the mouse gut. Following this first step, which consisted of inactivating a metabolic operon, one third of the subsequent adaptive mutations were found to have a selective effect as high as the first. Nevertheless, the order of the adaptive steps was strongly affected by a mutational hotspot with an exceptionally high mutation rate of 10-5. The pattern of polymorphism emerging in the populations evolving within different hosts was characterized by periodic selection, which reduced diversity, but also frequency-dependent selection, actively maintaining genetic diversity. Furthermore, the continuous emergence of similar phenotypes due to distinct mutations, known as clonal interference, was pervasive. Evolutionary change within the gut is therefore highly repeatable within and across hosts, with adaptive mutations of selection coefficients as strong as 12% accumulating without strong constraints on genetic background. In vivo competitive assays showed that one of the second steps (focA) exhibited positive epistasis with the first, while another (dcuB) exhibited negative epistasis. The data shows that strong effect adaptive mutations continuously recur in gut commensal bacterial species.
[Mh] Termos MeSH primário: Adaptação Fisiológica/genética
Transportadores de Ácidos Dicarboxílicos/genética
Epistasia Genética
Proteínas de Escherichia coli/genética
Proteínas de Membrana Transportadoras/genética
[Mh] Termos MeSH secundário: Alelos
Animais
Escherichia coli/genética
Escherichia coli/patogenicidade
Evolução Molecular
Microbioma Gastrointestinal/genética
Variação Genética
Camundongos
Mutação
Seleção Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dicarboxylic Acid Transporters); 0 (Escherichia coli Proteins); 0 (FocA protein, E coli); 0 (Membrane Transport Proteins); 0 (dcuB protein, E coli)
[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:161105
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1006420


  10 / 372 MEDLINE  
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[PMID]:27415771
[Au] Autor:Unden G; Strecker A; Kleefeld A; Kim OB
[Ad] Endereço:Institute for Microbiology und Wine Research, Johannes Gutenberg-University, 55099 Mainz, Germany.
[Ti] Título:C4-Dicarboxylate Utilization in Aerobic and Anaerobic Growth.
[So] Source:EcoSal Plus;7(1), 2016 06.
[Is] ISSN:2324-6200
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:C4-dicarboxylates and the C4-dicarboxylic amino acid l-aspartate support aerobic and anaerobic growth of Escherichia coli and related bacteria. In aerobic growth, succinate, fumarate, D- and L-malate, L-aspartate, and L-tartrate are metabolized by the citric acid cycle and associated reactions. Because of the interruption of the citric acid cycle under anaerobic conditions, anaerobic metabolism of C4-dicarboxylates depends on fumarate reduction to succinate (fumarate respiration). In some related bacteria (e.g., Klebsiella), utilization of C4-dicarboxylates, such as tartrate, is independent of fumarate respiration and uses a Na+-dependent membrane-bound oxaloacetate decarboxylase. Uptake of the C4-dicarboxylates into the bacteria (and anaerobic export of succinate) is achieved under aerobic and anaerobic conditions by different sets of secondary transporters. Expression of the genes for C4-dicarboxylate metabolism is induced in the presence of external C4-dicarboxylates by the membrane-bound DcuS-DcuR two-component system. Noncommon C4-dicarboxylates like l-tartrate or D-malate are perceived by cytoplasmic one-component sensors/transcriptional regulators. This article describes the pathways of aerobic and anaerobic C4-dicarboxylate metabolism and their regulation. The citric acid cycle, fumarate respiration, and fumarate reductase are covered in other articles and discussed here only in the context of C4-dicarboxylate metabolism. Recent aspects of C4-dicarboxylate metabolism like transport, sensing, and regulation will be treated in more detail. This article is an updated version of an article published in 2004 in EcoSal Plus. The update includes new literature, but, in particular, the sections on the metabolism of noncommon C4-dicarboxylates and their regulation, on the DcuS-DcuR regulatory system, and on succinate production by engineered E. coli are largely revised or new.
[Mh] Termos MeSH primário: Transportadores de Ácidos Dicarboxílicos/metabolismo
Ácidos Dicarboxílicos/metabolismo
Proteínas de Escherichia coli/genética
Escherichia coli/crescimento & desenvolvimento
Escherichia coli/metabolismo
[Mh] Termos MeSH secundário: Aerobiose
Anaerobiose
Transporte Biológico
Carboxiliases/metabolismo
Ciclo do Ácido Cítrico
Transportadores de Ácidos Dicarboxílicos/genética
Escherichia coli/genética
Proteínas de Escherichia coli/metabolismo
Fumaratos/metabolismo
Regulação Bacteriana da Expressão Gênica
Seres Humanos
Klebsiella/metabolismo
Proteínas de Membrana Transportadoras/metabolismo
Ácido Succínico/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Dicarboxylic Acid Transporters); 0 (Dicarboxylic Acids); 0 (Escherichia coli Proteins); 0 (Fumarates); 0 (Membrane Transport Proteins); AB6MNQ6J6L (Succinic Acid); EC 4.1.1.- (Carboxy-Lyases); EC 4.1.1.3 (oxaloacetate decarboxylase)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171126
[Lr] Data última revisão:
171126
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160715
[St] Status:MEDLINE
[do] DOI:10.1128/ecosalplus.ESP-0021-2015



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