Base de dados : MEDLINE
Pesquisa : D12.776.157.530.450.250.812.750 [Categoria DeCS]
Referências encontradas : 350 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 35 ir para página                         

  1 / 350 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28615288
[Au] Autor:Severance AC; Sandoval PJ; Wright SH
[Ad] Endereço:Department of Physiology, College of Medicine, University of Arizona, Tucson, Arizona.
[Ti] Título:Correlation between Apparent Substrate Affinity and OCT2 Transport Turnover.
[So] Source:J Pharmacol Exp Ther;362(3):405-412, 2017 Sep.
[Is] ISSN:1521-0103
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Organic cation (OC) transporter 2 (OCT2) mediates the first step in the renal secretion of many cationic drugs: basolateral uptake from blood into proximal tubule cells. The impact of this process on the pharmacokinetics of drug clearance as estimated using a physiologically-based pharmacokinetic approach relies on an accurate understanding of the kinetics of transport because the ratio of the maximal rate of transport to the Michaelis constant (i.e., J / K ) provides an estimate of the intrinsic clearance (Cl ) used in in vitro-in vivo extrapolation of experimentally determined transport data. Although the multispecificity of renal OC secretion, including that of the OCT2 transporter, is widely acknowledged, the possible relationship between relative affinity of the transporter for its diverse substrates and the maximal rates of their transport has received little attention. In this study, we determined the J and apparent Michaelis constant (K ) values for six structurally distinct OCT2 substrates and found a strong correlation between J and K ; high-affinity substrates [K values <50 M, including 1-methyl-4-phenylpyridinium, or 1-methyl-4-phenylpyridinium (MPP), and cimetidine] displayed systematically lower J values (<50 pmol cm min ) than did low-affinity substrates (K >200 M, including choline and metformin). Similarly, preloading OCT2-expressing cells with low-affinity substrates resulted in systematically larger -stimulated rates of MPP uptake than did preloading with high-affinity substrates. The data are quantitatively consistent with the hypothesis that dissociation of bound substrate from the transporter is rate limiting in establishing maximal rates of OCT2-mediated transport. This systematic relationship may provide a means to estimate Cl for drugs for which transport data are lacking.
[Mh] Termos MeSH primário: Proteínas de Transporte de Cátions Orgânicos/metabolismo
[Mh] Termos MeSH secundário: Animais
Transporte Biológico Ativo/genética
Células CHO
Cátions/metabolismo
Cricetinae
Cricetulus
Seres Humanos
Cinética
Proteínas de Transporte de Cátions Orgânicos/genética
Preparações Farmacêuticas/metabolismo
Membro 5 da Família 22 de Carreadores de Soluto
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cations); 0 (Organic Cation Transport Proteins); 0 (Pharmaceutical Preparations); 0 (SLC22A5 protein, human); 0 (Solute Carrier Family 22 Member 5)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170616
[St] Status:MEDLINE
[do] DOI:10.1124/jpet.117.242552


  2 / 350 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28298333
[Au] Autor:Shaw A; Jeromson S; Watterson KR; Pediani JD; Gallagher IJ; Whalley T; Dreczkowski G; Brooks N; Galloway SD; Hamilton DL
[Ad] Endereço:Physiology, Exercise and Nutrition Research Group, Faculty of Health Sciences and Sport, University of Stirling, Stirling, United Kingdom.
[Ti] Título:Multiple AMPK activators inhibit l-carnitine uptake in C2C12 skeletal muscle myotubes.
[So] Source:Am J Physiol Cell Physiol;312(6):C689-C696, 2017 Jun 01.
[Is] ISSN:1522-1563
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mutations in the gene that encodes the principal l-carnitine transporter, OCTN2, can lead to a reduced intracellular l-carnitine pool and the disease Primary Carnitine Deficiency. l-Carnitine supplementation is used therapeutically to increase intracellular l-carnitine. As AMPK and insulin regulate fat metabolism and substrate uptake, we hypothesized that AMPK-activating compounds and insulin would increase l-carnitine uptake in C2C12 myotubes. The cells express all three OCTN transporters at the mRNA level, and immunohistochemistry confirmed expression at the protein level. Contrary to our hypothesis, despite significant activation of PKB and 2DG uptake, insulin did not increase l-carnitine uptake at 100 nM. However, l-carnitine uptake was modestly increased at a dose of 150 nM insulin. A range of AMPK activators that increase intracellular calcium content [caffeine (10 mM, 5 mM, 1 mM, 0.5 mM), A23187 (10 µM)], inhibit mitochondrial function [sodium azide (75 µM), rotenone (1 µM), berberine (100 µM), DNP (500 µM)], or directly activate AMPK [AICAR (250 µM)] were assessed for their ability to regulate l-carnitine uptake. All compounds tested significantly inhibited l-carnitine uptake. Inhibition by caffeine was not dantrolene (10 µM) sensitive despite dantrolene inhibiting caffeine-mediated calcium release. Saturation curve analysis suggested that caffeine did not competitively inhibit l-carnitine transport. To assess the potential role of AMPK in this process, we assessed the ability of the AMPK inhibitor Compound C (10 µM) to rescue the effect of caffeine. Compound C offered a partial rescue of l-carnitine uptake with 0.5 mM caffeine, suggesting that AMPK may play a role in the inhibitory effects of caffeine. However, caffeine likely inhibits l-carnitine uptake by alternative mechanisms independently of calcium release. PKA activation or direct interference with transporter function may play a role.
[Mh] Termos MeSH primário: Carnitina/antagonistas & inibidores
Ativadores de Enzimas/farmacologia
Mioblastos/efeitos dos fármacos
Proteínas de Transporte de Cátions Orgânicos/metabolismo
[Mh] Termos MeSH secundário: Proteínas Quinases Ativadas por AMP/genética
Proteínas Quinases Ativadas por AMP/metabolismo
Aminoimidazol Carboxamida/análogos & derivados
Aminoimidazol Carboxamida/farmacologia
Animais
Berberina/farmacologia
Transporte Biológico/efeitos dos fármacos
Cafeína/farmacologia
Calcimicina/farmacologia
Cálcio/metabolismo
Carnitina/metabolismo
Linhagem Celular
Dantroleno/farmacologia
Ativação Enzimática/efeitos dos fármacos
Expressão Gênica
Insulina/farmacologia
Camundongos
Mioblastos/citologia
Mioblastos/enzimologia
Proteínas de Transporte de Cátions Orgânicos/genética
Isoformas de Proteínas/agonistas
Isoformas de Proteínas/genética
Isoformas de Proteínas/metabolismo
Ribonucleotídeos/farmacologia
Rotenona/farmacologia
Azida Sódica/farmacologia
Membro 5 da Família 22 de Carreadores de Soluto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enzyme Activators); 0 (Insulin); 0 (Organic Cation Transport Proteins); 0 (Protein Isoforms); 0 (Ribonucleotides); 0 (Slc22a5 protein, mouse); 0 (Solute Carrier Family 22 Member 5); 03L9OT429T (Rotenone); 0I8Y3P32UF (Berberine); 360-97-4 (Aminoimidazole Carboxamide); 37H9VM9WZL (Calcimycin); 3G6A5W338E (Caffeine); 968JJ8C9DV (Sodium Azide); EC 2.7.11.31 (AMP-Activated Protein Kinases); F0X88YW0YK (AICA ribonucleotide); F64QU97QCR (Dantrolene); S7UI8SM58A (Carnitine); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170317
[St] Status:MEDLINE
[do] DOI:10.1152/ajpcell.00026.2016


  3 / 350 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28295041
[Au] Autor:Lahrouchi N; Lodder EM; Mansouri M; Tadros R; Zniber L; Adadi N; Clur SB; van Spaendonck-Zwarts KY; Postma AV; Sefiani A; Ratbi I; Bezzina CR
[Ad] Endereço:Department of Clinical and Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
[Ti] Título:Exome sequencing identifies primary carnitine deficiency in a family with cardiomyopathy and sudden death.
[So] Source:Eur J Hum Genet;25(6):783-787, 2017 Jun.
[Is] ISSN:1476-5438
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Pediatric cardiomyopathy is a rare but severe disease with high morbidity and mortality. The causes are poorly understood and can only be established in one-third of cases. Recent advances in genetic technologies, specifically next-generation sequencing, now allow for the detection of genetic causes of cardiomyopathy in a systematic and unbiased manner. This is particularly important given the large clinical variability among pediatric cardiomyopathy patients and the large number of genes (>100) implicated in the disorder. We report on the performance of whole-exome sequencing in members of a consanguineous family with a history of pediatric hypertrophic cardiomyopathy and sudden cardiac death, which led to the identification of a homozygous stop variant in the SLC22A5 gene, implicated in primary carnitine deficiency, as the likely genetic cause. Targeted carnitine tandem mass spectrometry analysis in the patient revealed complete absence of plasma-free carnitine and only trace levels of total carnitine, further supporting the causality of the SLC22A5 variant. l-carnitine supplementation in the proband led to a rapid and marked clinical improvement. This case illustrates the use of exome sequencing as a systematic and unbiased diagnostic tool in pediatric cardiomyopathy, providing an efficient route to the identification of the underlying cause, which lead to appropriate treatment and prevention of premature death.
[Mh] Termos MeSH primário: Cardiomiopatias/genética
Carnitina/deficiência
Códon de Terminação/genética
Proteínas de Transporte de Cátions Orgânicos/genética
[Mh] Termos MeSH secundário: Adulto
Cardiomiopatias/diagnóstico
Cardiomiopatias/tratamento farmacológico
Carnitina/sangue
Carnitina/uso terapêutico
Morte Súbita
Exoma
Feminino
Seres Humanos
Lactente
Masculino
Mutação
Linhagem
Membro 5 da Família 22 de Carreadores de Soluto
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Codon, Terminator); 0 (Organic Cation Transport Proteins); 0 (SLC22A5 protein, human); 0 (Solute Carrier Family 22 Member 5); S7UI8SM58A (Carnitine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170316
[St] Status:MEDLINE
[do] DOI:10.1038/ejhg.2017.22


  4 / 350 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28257821
[Au] Autor:Jurkiewicz D; Michalec K; Skowronek K; Nalecz KA
[Ad] Endereço:Laboratory of Transport Through Biomembranes, Nencki Institute of Experimental Biology of Polish Academy of Sciences, 3 Pasteur Street, 02-093 Warsaw, Poland.
[Ti] Título:Tight junction protein ZO-1 controls organic cation/carnitine transporter OCTN2 (SLC22A5) in a protein kinase C-dependent way.
[So] Source:Biochim Biophys Acta;1864(5):797-805, 2017 05.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:OCTN2 (SLC22A5) is an organic cation/carnitine transporter belonging to the solute carrier transporters (SLC) family. OCTN2 is ubiquitously expressed and its presence was shown in various brain cells, including the endothelial cells forming blood-brain barrier, where it was mainly detected at abluminal membrane and in proximity of tight junctions (TJ). Since OCTN2 contains a PDZ-binding domain, the present study was focused on a possible role of transporter interaction with a TJ-associated protein ZO-1, containing PDZ domains and detected in rat Octn2 proteome. We showed previously that activation of protein kinase C (PKC) in rat astrocytes regulates Octn2 surface presence and activity. Regulation of a wild type Octn2 and its deletion mutant without a PDZ binding motif were studied in heterologous expression system in HEK293 cells. Plasma membrane presence of overexpressed Octn2 did not depend on either PKC activation or presence of PDZ-binding motif, anyhow, as assayed in proximity ligation assay, the truncation of PDZ binding motif resulted in a strongly diminished Octn2/ZO-1 interaction and in a decreased transporter activity. The same effects on Octn2 activity were detected upon PKC activation, what correlated with ZO-1 phosphorylation. It is postulated that ZO-1, when not phosphorylated by PKC, keeps Octn2 in an active state, while elimination of this binding in ΔPDZ mutant or after ZO-1 phosphorylation leads to diminution of Octn2 activity.
[Mh] Termos MeSH primário: Proteínas de Transporte de Cátions Orgânicos/metabolismo
Proteína Quinase C/metabolismo
Proteína da Zônula de Oclusão-1/fisiologia
[Mh] Termos MeSH secundário: Animais
Cães
Células HEK293
Seres Humanos
Células Madin Darby de Rim Canino
Fosforilação
Ligação Proteica
Transdução de Sinais
Membro 5 da Família 22 de Carreadores de Soluto
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Organic Cation Transport Proteins); 0 (SLC22A5 protein, human); 0 (Solute Carrier Family 22 Member 5); 0 (TJP1 protein, human); 0 (Zonula Occludens-1 Protein); EC 2.7.11.13 (Protein Kinase C)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170305
[St] Status:MEDLINE


  5 / 350 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28234466
[Au] Autor:Wang G; Chen H; Zhao D; Ding D; Sun M; Kou L; Luo C; Zhang D; Yi X; Dong J; Wang J; Liu X; He Z; Sun J
[Ad] Endereço:School of Pharmacy, Shenyang Pharmaceutical University , Wenhua Road, Shenyang 110016, China.
[Ti] Título:Combination of l-Carnitine with Lipophilic Linkage-Donating Gemcitabine Derivatives as Intestinal Novel Organic Cation Transporter 2-Targeting Oral Prodrugs.
[So] Source:J Med Chem;60(6):2552-2561, 2017 Mar 23.
[Is] ISSN:1520-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Novel organic cation transporter 2 (OCTN2, SLC22A5) is responsible for the uptake of carnitine through the intestine and, therefore, might be a promising molecular target for designing oral prodrugs. Poor permeability and rapid metabolism have greatly restricted the oral absorption of gemcitabine. We here describe the design of intestinal OCTN2-targeting prodrugs of gemcitabine by covalent coupling of l-carnitine to its N4-amino group via different lipophilic linkages. Because of the high OCTN2 affinity, the hexane diacid-linked prodrug demonstrated significantly improved stability (3-fold), cellular permeability (15-fold), and oral bioavailability (5-fold), while causing no toxicity as compared to gemcitabine. In addition, OCTN2-targeting prodrugs can simultaneously improve the permeability, solubility, and metabolic stability of gemcitabine. In summary, we present the first evidence that OCTN2 can act as a new molecular target for oral prodrug delivery and, importantly, the linkage carbon chain length is a key factor in modifying the affinity of the substrate for OCTN2.
[Mh] Termos MeSH primário: Antimetabólitos Antineoplásicos/química
Antimetabólitos Antineoplásicos/farmacocinética
Desoxicitidina/análogos & derivados
Proteínas de Transporte de Cátions Orgânicos/metabolismo
Pró-Fármacos/química
Pró-Fármacos/farmacocinética
[Mh] Termos MeSH secundário: Animais
Antimetabólitos Antineoplásicos/metabolismo
Células CACO-2
Carnitina/química
Carnitina/metabolismo
Carnitina/farmacocinética
Desoxicitidina/química
Desoxicitidina/metabolismo
Desoxicitidina/farmacocinética
Células HEK293
Seres Humanos
Camundongos
Simulação de Acoplamento Molecular
Pró-Fármacos/metabolismo
Membro 5 da Família 22 de Carreadores de Soluto
Distribuição Tecidual
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antimetabolites, Antineoplastic); 0 (Organic Cation Transport Proteins); 0 (Prodrugs); 0 (SLC22A5 protein, human); 0 (Solute Carrier Family 22 Member 5); 0W860991D6 (Deoxycytidine); B76N6SBZ8R (gemcitabine); S7UI8SM58A (Carnitine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170225
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jmedchem.7b00049


  6 / 350 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28186590
[Au] Autor:Lin Y; Lin W; Yu K; Zheng F; Zheng Z; Fu Q
[Ad] Endereço:Neonatal Disease Screening Center in Quanzhou, Quanzhou Women's and Children's Hospital, Quanzhou, Fujian 362000, China. wrightlym@sina.com.
[Ti] Título:[Mutational analysis of SLC22A5 gene in eight patients with systemic primary carnitine deficiency].
[So] Source:Zhonghua Yi Xue Yi Chuan Xue Za Zhi;34(1):35-39, 2017 Feb 10.
[Is] ISSN:1003-9406
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:OBJECTIVE: To investigate the mutations of SLC22A5 gene in patients with systemic primary carnitine deficiency (CDSP). METHODS: High liquid chromatography tandem mass spectrometry (HPLC/MS/MS) was applied to screen congenital genetic metabolic disease and eight patients with CDSP were diagnosed among 77 511 samples. The SLC22A5 gene mutation was detected using massarray technology and sanger sequencing. Using SIFT and PolyPhen-2 to predict the function of protein for novel variations. RESULTS: Total detection rate of gene mutation is 100% in the eight patients with CDSP. Seven patients had compound heterozygous mutations and one patient had homozygous mutations. Six different mutations were identified, including one nonsense mutation [c.760C>T(p.R254X)] and five missense mutations[c.51C>G(p.F17L), c.250T>A(p.Y84N), c.1195C>T(p.R399W), c.1196G>A(p.R399Q), c.1400C>G(p.S467C)]. The c.250T>A(p.Y84N) was a novel variation, the novel variation was predicted to have affected protein structure and function. The c.760C>T (p.R254X)was the most frequently seen mutation, which was followed by the c.1400C>G(p.S467C). CONCLUSION: This study confirmed the diagnosis of eight patients with CDSP on the gene level. Six mutations were found in the SLC22A5 gene, including one novel mutation which expanded the mutational spectrum of the SLC22A5 gene.
[Mh] Termos MeSH primário: Cardiomiopatias/genética
Carnitina/deficiência
Hiperamonemia/genética
Doenças Musculares/genética
Mutação
Proteínas de Transporte de Cátions Orgânicos/genética
[Mh] Termos MeSH secundário: Adulto
Sequência de Aminoácidos
Sequência de Bases
Cardiomiopatias/diagnóstico
Cardiomiopatias/metabolismo
Carnitina/genética
Carnitina/metabolismo
Análise Mutacional de DNA/métodos
Feminino
Frequência do Gene
Genótipo
Seres Humanos
Hiperamonemia/diagnóstico
Hiperamonemia/metabolismo
Recém-Nascido
Masculino
Doenças Musculares/diagnóstico
Doenças Musculares/metabolismo
Proteínas de Transporte de Cátions Orgânicos/metabolismo
Reprodutibilidade dos Testes
Sensibilidade e Especificidade
Homologia de Sequência de Aminoácidos
Membro 5 da Família 22 de Carreadores de Soluto
Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Organic Cation Transport Proteins); 0 (SLC22A5 protein, human); 0 (Solute Carrier Family 22 Member 5); S7UI8SM58A (Carnitine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170211
[St] Status:MEDLINE
[do] DOI:10.3760/cma.j.issn.1003-9406.2017.01.008


  7 / 350 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27983775
[Au] Autor:Liepinsh E; Makarova E; Sevostjanovs E; Hartmane D; Cirule H; Zharkova-Malkova O; Grinberga S; Dambrova M
[Ad] Endereço:Latvian Institute of Organic Synthesis, Riga, Latvia.
[Ti] Título:Carnitine and γ-Butyrobetaine Stimulate Elimination of Meldonium due to Competition for OCTN2-mediated Transport.
[So] Source:Basic Clin Pharmacol Toxicol;120(5):450-456, 2017 May.
[Is] ISSN:1742-7843
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Meldonium (3-(2,2,2-trimethylhydrazinium)propionate) is the most potent clinically used inhibitor of organic cation transporter 2 (OCTN2). Inhibition of OCTN2 leads to a decrease in carnitine and acylcarnitine contents in tissues and energy metabolism optimization-related cardioprotective effects. The recent inclusion of meldonium in the World Anti-Doping Agency List of Prohibited Substances and Methods has raised questions about the pharmacokinetics of meldonium and its unusually long elimination time. Therefore, in this study, the rate of meldonium washout after the end of the treatment was tested with and without administration of carnitine, γ-butyrobetaine (GBB) and furosemide to evaluate the importance of competition for OCTN2 transport in mice. Here, we show that carnitine and GBB administration during the washout period effectively stimulated the elimination of meldonium. GBB induced a more pronounced effect on meldonium elimination than carnitine due to the higher affinity of GBB for OCTN2. The diuretic effect of furosemide did not significantly affect the elimination of meldonium, carnitine and GBB. In conclusion, the competition of meldonium, carnitine and GBB for OCTN2-mediated transport determines the pharmacokinetic properties of meldonium. Thus, due to their affinity for OCTN2, GBB and carnitine but not furosemide stimulated meldonium elimination. During long-term treatment, OCTN2-mediated transport ensures a high muscle content of meldonium, while tissue clearance depends on relatively slow diffusion, thus resulting in the unusually long complete elimination period of meldonium.
[Mh] Termos MeSH primário: Betaína/análogos & derivados
Carnitina/administração & dosagem
Metilidrazinas/farmacocinética
Proteínas de Transporte de Cátions Orgânicos/metabolismo
[Mh] Termos MeSH secundário: Animais
Betaína/administração & dosagem
Betaína/farmacocinética
Betaína/farmacologia
Transporte Biológico/efeitos dos fármacos
Carnitina/farmacocinética
Carnitina/farmacologia
Furosemida/administração & dosagem
Furosemida/farmacologia
Masculino
Metilidrazinas/farmacologia
Camundongos
Proteínas de Transporte de Cátions Orgânicos/antagonistas & inibidores
Membro 5 da Família 22 de Carreadores de Soluto
Distribuição Tecidual
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Methylhydrazines); 0 (Organic Cation Transport Proteins); 0 (Slc22a5 protein, mouse); 0 (Solute Carrier Family 22 Member 5); 3SCV180C9W (Betaine); 407-64-7 (gamma-butyrobetaine); 73H7UDN6EC (3-(2,2,2-trimethylhydrazine)propionate); 7LXU5N7ZO5 (Furosemide); S7UI8SM58A (Carnitine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161217
[St] Status:MEDLINE
[do] DOI:10.1111/bcpt.12729


  8 / 350 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27733576
[Au] Autor:Ingoglia F; Visigalli R; Rotoli BM; Barilli A; Riccardi B; Puccini P; Milioli M; Di Lascia M; Bernuzzi G; Dall'Asta V
[Ad] Endereço:Department of Biomedical, Biotechnological and Translational Sciences, University of Parma, Parma, Italy.
[Ti] Título:Human macrophage differentiation induces OCTN2-mediated L-carnitine transport through stimulation of mTOR-STAT3 axis.
[So] Source:J Leukoc Biol;101(3):665-674, 2017 Mar.
[Is] ISSN:1938-3673
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:l-Carnitine, in addition to playing a fundamental role in the ß-oxidation of fatty acids, has been recently identified as a modulator of immune function, although the mechanisms that underlie this role remain to be clarified. In this study, we addressed the modulation of l-carnitine transport and expression of related transporters during differentiation of human monocytes to macrophages. Whereas monocytes display a modest uptake of l-carnitine, GM-CSF-induced differentiation massively increased the saturable Na -dependent uptake of l-carnitine. Kinetic and inhibition analyses demonstrate that in macrophage l-carnitine transport is mediated by a high-affinity component (K ∼4 µM) that is identifiable with the operation of OCTN2 transporter and a low-affinity component (K > 10 mM) that is identifiable with system A for neutral amino acids. Consistently, both SLC22A5/OCTN2 and SLC38A2/SNAT2 are induced during the differentiation of monocytes to macrophages at gene and protein levels. Elucidation of GM-CSF signaling demonstrates that the cytokine causes the activation of mTOR kinase, leading to the phosphorylation and activation of STAT3, which, in turn, is responsible for OCTN2 transcription. SLC22A5/OCTN2 therefore emerges as a novel member of the set of genes markers of macrophage differentiation.
[Mh] Termos MeSH primário: Carnitina/metabolismo
Diferenciação Celular
Macrófagos/citologia
Macrófagos/metabolismo
Proteínas de Transporte de Cátions Orgânicos/metabolismo
Fator de Transcrição STAT3/metabolismo
Transdução de Sinais
Serina-Treonina Quinases TOR/metabolismo
[Mh] Termos MeSH secundário: Transporte Biológico
Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo
Seres Humanos
Cinética
Modelos Biológicos
Monócitos/citologia
Proteínas de Transporte de Cátions Orgânicos/genética
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Membro 5 da Família 22 de Carreadores de Soluto
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Organic Cation Transport Proteins); 0 (RNA, Messenger); 0 (SLC22A5 protein, human); 0 (STAT3 Transcription Factor); 0 (Solute Carrier Family 22 Member 5); 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor); EC 2.7.1.1 (TOR Serine-Threonine Kinases); S7UI8SM58A (Carnitine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161014
[St] Status:MEDLINE
[do] DOI:10.1189/jlb.1A0616-254R


  9 / 350 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27537937
[Au] Autor:Juraszek B; Nalecz KA
[Ad] Endereço:Laboratory of Transport through Biomembranes, Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Warsaw, Poland.
[Ti] Título:Protein phosphatase PP2A - a novel interacting partner of carnitine transporter OCTN2 (SLC22A5) in rat astrocytes.
[So] Source:J Neurochem;139(4):537-551, 2016 Nov.
[Is] ISSN:1471-4159
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:l-Carnitine is essential for translocation of fatty acids for their mitochondrial ß-oxidation, a process shown in the brain to take place in astrocytes. Organic cation and carnitine plasma membrane transporter OCTN2 (SLC22A5) is present in astrocytes. OCTN2 activity and localization were previously shown to be regulated by protein kinase C (PKC), although no phosphorylation of the transporter was detected. In this study, mass spectrometry was used to identify rOctn2-interacting partners in astrocytes: several cytoskeletal, ribosomal, mitochondrial, heat-shock proteins, as well as proteins involved in trafficking and signaling pathways. The analysis of signaling proteins shows that Octn2 co-precipitated with PP2A phosphatase catalytical (C) and structural (A) subunits, and with its regulatory B"' subunits - striatin, SG2NA, and zinedin. The Octn2/PP2A complex is mainly detected in endoplasmic reticulum. PKC activation increases both, carnitine transport and, as shown by immunofluorescence and surface biotinylation, transporter presence in plasma membrane. It also results in phosphorylation of SG2NA, zinedin, and catalytical subunit, although co-precipitation, immunocytochemistry, and proximity ligation assay experiments showed that only the amount of SG2NA decreased in the complex with Octn2. PP2A inhibition with okadaic acid does not lead to Octn2 phosphorylation; however, it abolishes observed effects of PKC activation. We postulate that PKC phosphorylates SG2NA, resulting in its dissociation from the complex and transfer of Octn2 to the plasma membrane, leading to increased transporter activity. The observed interaction could affect brain functioning in vivo, both in fatty acid metabolism and in control of carnitine homeostasis, known to change in certain brain pathologies.
[Mh] Termos MeSH primário: Astrócitos/metabolismo
Proteínas de Transporte de Cátions Orgânicos/metabolismo
Proteína Fosfatase 2/metabolismo
[Mh] Termos MeSH secundário: Animais
Astrócitos/efeitos dos fármacos
Membrana Celular/efeitos dos fármacos
Membrana Celular/metabolismo
Células Cultivadas
Ácido Okadáico/farmacologia
Ligação Proteica/fisiologia
Proteína Fosfatase 2/antagonistas & inibidores
Ratos
Ratos Wistar
Membro 5 da Família 22 de Carreadores de Soluto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Organic Cation Transport Proteins); 0 (Slc22a5 protein, rat); 0 (Solute Carrier Family 22 Member 5); 1W21G5Q4N2 (Okadaic Acid); EC 3.1.3.16 (Protein Phosphatase 2)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160819
[St] Status:MEDLINE
[do] DOI:10.1111/jnc.13777


  10 / 350 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27503646
[Au] Autor:Yang X; Ma Z; Zhou S; Weng Y; Lei H; Zeng S; Li L; Jiang H
[Ad] Endereço:Laboratory of Pharmaceutical Analysis and Drug Metabolism, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.
[Ti] Título:Multiple Drug Transporters Are Involved in Renal Secretion of Entecavir.
[So] Source:Antimicrob Agents Chemother;60(10):6260-70, 2016 Oct.
[Is] ISSN:1098-6596
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Entecavir (ETV) is a first-line antiviral agent for the treatment of chronic hepatitis B virus infection. Renal excretion is the major elimination path of ETV, in which tubular secretion plays the key role. However, the secretion mechanism has not been clarified. We speculated that renal transporters mediated the secretion of ETV. Therefore, the aim of our study was to elucidate which transporters contribute to the renal disposition of ETV. Our results revealed that ETV (50 µM) remarkably reduced the accumulation of probe substrates in MDCK cells stably expressing human multidrug and toxin efflux extrusion proteins (hMATE1/2-K), organic cation transporter 2 (hOCT2), and carnitine/organic cation transporters (hOCTNs) and increased the substrate accumulation in cells transfected with multidrug resistance-associated protein 2 (hMRP2) or multidrug resistance protein 1 (hMDR1). Moreover, ETV was proved to be a substrate of the above-described transporters. In transwell studies, the transport of ETV in MDCK-hOCT2-hMATE1 showed a distinct directionality from BL (hOCT2) to AP (hMATE1), and the cellular accumulation of ETV in cells expressing hMATE1 was dramatically lower than that of the mock-treated cells. The accumulation of ETV in mouse primary renal tubular cells was obviously affected by inhibitors of organic anion transporter 1/3 (Oat1/3), Oct2, Octn1/2, and Mrp2. Therefore, the renal uptake of ETV is likely mediated by OAT1/3 and OCT2 while the efflux is mediated by MATEs, MDR1, and MRP2, and OCTN1/2 may participate in both renal secretion and reabsorption.
[Mh] Termos MeSH primário: Guanina/análogos & derivados
Rim/efeitos dos fármacos
Proteínas de Membrana Transportadoras/metabolismo
[Mh] Termos MeSH secundário: Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo
Animais
Cães
Guanina/farmacocinética
Seres Humanos
Rim/metabolismo
Células Madin Darby de Rim Canino
Masculino
Proteínas de Membrana Transportadoras/genética
Camundongos Endogâmicos ICR
Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética
Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo
Proteínas de Transporte de Cátions Orgânicos/genética
Proteínas de Transporte de Cátions Orgânicos/metabolismo
Transportador 2 de Cátion Orgânico
Membro 5 da Família 22 de Carreadores de Soluto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ATP-Binding Cassette, Sub-Family B, Member 1); 0 (MATE1 protein, human); 0 (MATE2-K protein, human); 0 (Membrane Transport Proteins); 0 (Multidrug Resistance-Associated Proteins); 0 (Organic Cation Transport Proteins); 0 (Organic Cation Transporter 2); 0 (SLC22A2 protein, human); 0 (SLC22A4 protein, human); 0 (SLC22A5 protein, human); 0 (Solute Carrier Family 22 Member 5); 4AF605U6JN (multidrug resistance-associated protein 2); 5968Y6H45M (entecavir); 5Z93L87A1R (Guanine)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160810
[St] Status:MEDLINE
[do] DOI:10.1128/AAC.00986-16



página 1 de 35 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