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[PMID]:28768834
[Au] Autor:Batistel F; Alharthi AS; Wang L; Parys C; Pan YX; Cardoso FC; Loor JJ
[Ad] Endereço:Division of Nutritional Sciences, Departments of Animal Sciences and.
[Ti] Título:Placentome Nutrient Transporters and Mammalian Target of Rapamycin Signaling Proteins Are Altered by the Methionine Supply during Late Gestation in Dairy Cows and Are Associated with Newborn Birth Weight.
[So] Source:J Nutr;147(9):1640-1647, 2017 Sep.
[Is] ISSN:1541-6100
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:To our knowledge, most research demonstrating a link between maternal nutrition and both fetal growth and offspring development after birth has been performed with nonruminants. Whether such relationships exist in large ruminants is largely unknown. We aimed to investigate whether increasing the methionine supply during late pregnancy would alter uteroplacental tissue nutrient transporters and mammalian target of rapamycin (mTOR) and their relation with newborn body weight. Multiparous Holstein cows were used in a randomized complete block design experiment. During the last 28 d of pregnancy, cows were fed a control diet or the control diet plus ethylcellulose rumen-protected methionine (0.9 g/kg dry matter intake) (Mepron; Evonik Nutrition & Care GmbH) to achieve a 2.8:1 ratio of lysine to methionine in the metabolizable protein reaching the small intestine. We collected placentome samples at parturition and used them to assess mRNA and protein expression and the phosphorylation status of mTOR pathway proteins. Newborn body weight was greater in the methionine group than in the control group (44.1 kg and 41.8 kg, respectively; ≤ 0.05). Increasing the methionine supply also resulted in greater feed intake (15.8 kg/d and 14.6 kg/d), plasma methionine (11.9 µM and 15.3 µM), and plasma insulin (1.16 µg/L and 0.81 µg/L) in cows during late pregnancy. As a result, mRNA expression of genes involved in neutral amino acid transport [solute carrier (SLC) family members , , , and ], glucose transport [ , , and ], and the mTOR pathway [mechanistic target of rapamycin and ribosomal protein S6 kinase B1] were upregulated ( ≤ 0.07) in methionine-supplemented cows. Among 6 proteins in the mTOR pathway, increasing the methionine supply led to greater ( ≤ 0.09) protein expression of α serine-threonine kinase (AKT), phosphorylated (p)-AKT, p-eukaryotic elongation factor 2, and the p-mTOR:mTOR ratio. Supplemental methionine during late gestation increases feed intake and newborn body weight in dairy cows, and this effect may be mediated by alterations in the uteroplacental transport of nondispensable and dispensable amino acids and glucose at least in part through changes in gene transcription and mTOR signaling.
[Mh] Termos MeSH primário: Fenômenos Fisiológicos da Nutrição Animal
Peso ao Nascer/efeitos dos fármacos
Metionina/farmacologia
Placenta/metabolismo
Fenômenos Fisiológicos da Nutrição Pré-Natal
Proteínas Carreadoras de Solutos/metabolismo
Serina-Treonina Quinases TOR/metabolismo
[Mh] Termos MeSH secundário: Animais
Animais Recém-Nascidos
Bovinos
Dieta/veterinária
Suplementos Nutricionais
Ingestão de Energia/efeitos dos fármacos
Feminino
Idade Gestacional
Glucose/metabolismo
Insulina/sangue
Intestino Delgado
Lisina/administração & dosagem
Metionina/administração & dosagem
Metionina/sangue
Gravidez
RNA Mensageiro/metabolismo
Distribuição Aleatória
Proteínas Carreadoras de Solutos/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Insulin); 0 (RNA, Messenger); 0 (Solute Carrier Proteins); AE28F7PNPL (Methionine); EC 2.7.1.1 (TOR Serine-Threonine Kinases); IY9XDZ35W2 (Glucose); K3Z4F929H6 (Lysine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170913
[Lr] Data última revisão:
170913
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170804
[St] Status:MEDLINE
[do] DOI:10.3945/jn.117.251876


  2 / 20 MEDLINE  
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[PMID]:28756021
[Au] Autor:Pereira SV; Ribeiro JD; Bertuzzo CS; Marson FAL
[Ad] Endereço:Department of Medical Genetics, Faculty of Medical Sciences, State University of Campinas, Tessália Vieira de Camargo, 126, Barão Geraldo, Cidade Universitária Zeferino Vaz, 13083-887 Campinas, São Paulo, Brazil. Electronic address: ste.vnp@hotmail.com.
[Ti] Título:Association of clinical severity of cystic fibrosis with variants in the SLC gene family (SLC6A14, SLC26A9, SLC11A1 and SLC9A3).
[So] Source:Gene;629:117-126, 2017 Sep 20.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Cystic fibrosis (CF) manifests with clinical and histopathological variability depending on environmental and genetic factors. Moreover, the genes encoding ion channels[rs3788766(SLC6A14), rs7512462(SLC26A9), rs17235416(SLC11A1) and rs17563161(SLC9A3)] have been insufficiently studied as modifier genes. Then, our objective was associate the variants in the genes of SLC family with 43 CF severity markers. METHODS: The variants were identified by real-time-PCR in 188 CF patients considering the CFTR genotype. Statistical analyses were performed by parametric and nonparametric tests. The correction by multiple testing was performed by the False Rate Discovery test, alpha=0.05. RESULTS: Depending on the CFTR mutations, we found association of: (i) rs3788766*CC with mucoid Pseudomonas aeruginosa (OR=0.171; 95%CI=0.029-0.696), non-mucoid P. aeruginosa (OR=0.283; 95%CI=0.094-0.853) and Staphyloccocus aureus (OR=4.443; 95%CI=1.019-40.64), largest FEF (p=0.041) and best response to bronchodilator for FEF (p=0.033) and FEV /FVC(p=0.044); (ii) rs3788766*CT with early start of pulmonary symptom (OR=3.524; 95%CI=1.229-10.1) and osteoporosis (OR=0.203; 95%CI=0.022-0.883); (iii) rs3788766*TT with lowest body mass index (OR=4.242; 95%CI=1.505-11.95), presence of mucoid P. aeruginosa (OR=3.176; 95%CI=1.29-7.819) and S. aureus (OR=0.116; 95%CI=0.004-0.881), highest Bhalla score (p=0.047) and lowest FEF (p=0.028) and FEF (p=0.031) values; (iv) rs7512462*CC with highest Shwachman-Kulczycki score (p=0.019), FVC(p=0.043), FEV (p=0.047), FEV /FVC(p=0.022), FEF (p=0.038) and FEF (p=0.016); (v) rs7512462*CT with lowest values of FVC(p=0.034), FEV (p=0.047), FEV /FVC(p=0.022), FEF (p=0.012), FEF (p=0.038), FEF (p=0.008), FEF (p=0.016) and ERV(p=0.023); (vi) rs7512462*TT with best response to the inhaled bronchodilator for FEV (p=0.011), FEF (p=0.019), FEF (p=0.036) and FEF (p=0.008); (vii) rs17234516*Normal allele with lowest value of SaO (p=0.010) and S. aureus (OR=3.333; 95%CI=1.085-10.24); (viii) rs17563161*GG with lowest age for onset of digestive symptoms (OR=2.564; 95%CI=1.234-5.33). CONCLUSIONS: The clinical and laboratory variability of CF were associated with the variants in the genes of SLC family in our sample.
[Mh] Termos MeSH primário: Fibrose Cística/genética
Fibrose Cística/patologia
Polimorfismo de Nucleotídeo Único
Proteínas Carreadoras de Solutos/genética
[Mh] Termos MeSH secundário: Regulador de Condutância Transmembrana em Fibrose Cística/genética
Seres Humanos
Reação em Cadeia da Polimerase em Tempo Real
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CFTR protein, human); 0 (Solute Carrier Proteins); 126880-72-6 (Cystic Fibrosis Transmembrane Conductance Regulator)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170828
[Lr] Data última revisão:
170828
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170731
[St] Status:MEDLINE


  3 / 20 MEDLINE  
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[PMID]:28425971
[Au] Autor:Medina AB; Banaszczak M; Ni Y; Aretz I; Meierhofer D
[Ad] Endereço:Max Planck Institute for Molecular Genetics, Ihnestraße 63-73, 14195 Berlin, Germany. andrebmedina@gmail.com.
[Ti] Título:ρ° Cells Feature De-Ubiquitination of SLC Transporters and Increased Levels and Fluxes of Amino Acids.
[So] Source:Int J Mol Sci;18(4), 2017 04 20.
[Is] ISSN:1422-0067
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Solute carrier (SLC) transporters are a diverse group of membrane transporter proteins that regulate the cellular flux and distribution of endogenous and xenobiotic compounds. Post-translational modifications (PTMs), such as ubiquitination, have recently emerged as one of the major regulatory mechanisms in protein function and localization. Previously, we showed that SLC amino acid transporters were on average 6-fold de-ubiquitinated and increased amino acid levels were detected in ρ° cells (lacking mitochondrial DNA, mtDNA) compared to parental cells. Here, we elucidated the altered functionality of SLC transporters and their dynamic ubiquitination status by measuring the uptake of several isotopically labeled amino acids in both human osteosarcoma 143B.TK- and ρ° cells. Our pulse chase analysis indicated that de-ubiquitinated amino acid transporters in ρ° cells were accompanied by an increased transport rate, which leads to higher levels of amino acids in the cell. Finding SLC transport enhancers is an aim of the pharmaceutical industry in order to compensate for loss of function mutations in these genes. Thus, the ubiquitination status of SLC transporters could be an indicator for their functionality, but evidence for a direct connection between de-ubiquitination and transporter activity has to be further elucidated.
[Mh] Termos MeSH primário: Aminoácidos/metabolismo
Proteínas Carreadoras de Solutos/metabolismo
[Mh] Termos MeSH secundário: Transporte Biológico
Linhagem Celular Tumoral
Seres Humanos
Metaboloma
Metabolômica/métodos
Processamento de Proteína Pós-Traducional
Ubiquitinação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acids); 0 (Solute Carrier Proteins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170421
[St] Status:MEDLINE


  4 / 20 MEDLINE  
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[PMID]:28375174
[Au] Autor:Mayati A; Moreau A; Le Vée M; Stieger B; Denizot C; Parmentier Y; Fardel O
[Ad] Endereço:Institut de Recherches en Santé, Environnement et Travail (IRSET), UMR INSERM U1085, Faculté de Pharmacie, 2 Avenue du Pr Léon Bernard, 35043 Rennes, France. abdullah.mayati@univ-rennes1.fr.
[Ti] Título:Protein Kinases C-Mediated Regulations of Drug Transporter Activity, Localization and Expression.
[So] Source:Int J Mol Sci;18(4), 2017 Apr 04.
[Is] ISSN:1422-0067
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Drug transporters are now recognized as major actors in pharmacokinetics, involved notably in drug-drug interactions and drug adverse effects. Factors that govern their activity, localization and expression are therefore important to consider. In the present review, the implications of protein kinases C (PKCs) in transporter regulations are summarized and discussed. Both solute carrier (SLC) and ATP-binding cassette (ABC) drug transporters can be regulated by PKCs-related signaling pathways. PKCs thus target activity, membrane localization and/or expression level of major influx and efflux drug transporters, in various normal and pathological types of cells and tissues, often in a PKC isoform-specific manner. PKCs are notably implicated in membrane insertion of bile acid transporters in liver and, in this way, are thought to contribute to cholestatic or choleretic effects of endogenous compounds or drugs. The exact clinical relevance of PKCs-related regulation of drug transporters in terms of drug resistance, pharmacokinetics, drug-drug interactions and drug toxicity remains however to be precisely determined. This issue is likely important to consider in the context of the development of new drugs targeting PKCs-mediated signaling pathways, for treating notably cancers, diabetes or psychiatric disorders.
[Mh] Termos MeSH primário: Transportadores de Cassetes de Ligação de ATP/metabolismo
Proteína Quinase C/metabolismo
Transdução de Sinais
Proteínas Carreadoras de Solutos/metabolismo
[Mh] Termos MeSH secundário: Transportadores de Cassetes de Ligação de ATP/genética
Transporte Biológico
Regulação da Expressão Gênica
Seres Humanos
Isoenzimas/metabolismo
Preparações Farmacêuticas/metabolismo
Fosforilação
Proteínas Carreadoras de Solutos/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Isoenzymes); 0 (Pharmaceutical Preparations); 0 (Solute Carrier Proteins); EC 2.7.11.13 (Protein Kinase C)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170601
[Lr] Data última revisão:
170601
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170405
[St] Status:MEDLINE


  5 / 20 MEDLINE  
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[PMID]:28350329
[Au] Autor:Nyquist MD; Prasad B; Mostaghel EA
[Ad] Endereço:Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. mnyquist@fredhutch.org.
[Ti] Título:Harnessing Solute Carrier Transporters for Precision Oncology.
[So] Source:Molecules;22(4), 2017 Mar 28.
[Is] ISSN:1420-3049
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Solute Carrier (SLC) transporters are a large superfamily of transmembrane carriers involved in the regulated transport of metabolites, nutrients, ions and drugs across cellular membranes. A subset of these solute carriers play a significant role in the cellular uptake of many cancer therapeutics, ranging from chemotherapeutics such as antimetabolites, topoisomerase inhibitors, platinum-based drugs and taxanes to targeted therapies such as tyrosine kinase inhibitors. SLC transporters are co-expressed in groups and patterns across normal tissues, suggesting they may comprise a coordinated regulatory circuit serving to mediate normal tissue functions. In cancer however, there are dramatic changes in expression patterns of SLC transporters. This frequently serves to feed the increased metabolic demands of the tumor cell for amino acids, nucleotides and other metabolites, but also presents a therapeutic opportunity, as increased transporter expression may serve to increase intracellular concentrations of substrate drugs. In this review, we examine the regulation of drug transporters in cancer and how this impacts therapy response, and discuss novel approaches to targeting therapies to specific cancers via tumor-specific aberrations in transporter expression. We propose that among the oncogenic changes in SLC transporter expression there exist emergent vulnerabilities that can be exploited therapeutically, extending the application of precision medicine from tumor-specific drug targets to tumor-specific determinants of drug uptake.
[Mh] Termos MeSH primário: Antineoplásicos/farmacocinética
Neoplasias/tratamento farmacológico
Proteínas Carreadoras de Solutos/metabolismo
[Mh] Termos MeSH secundário: Antineoplásicos/uso terapêutico
Transporte Biológico
Ensaios Clínicos como Assunto
Seres Humanos
Terapia de Alvo Molecular
Neoplasias/metabolismo
Medicina de Precisão
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Solute Carrier Proteins)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170826
[Lr] Data última revisão:
170826
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170329
[St] Status:MEDLINE


  6 / 20 MEDLINE  
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[PMID]:28214518
[Au] Autor:Rives ML; Javitch JA; Wickenden AD
[Ad] Endereço:Molecular and Cellular Pharmacology, Discovery Sciences, Janssen R&D, San Diego, CA 92121, United States.
[Ti] Título:Potentiating SLC transporter activity: Emerging drug discovery opportunities.
[So] Source:Biochem Pharmacol;135:1-11, 2017 Jul 01.
[Is] ISSN:1873-2968
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Maintaining the integrity of cellular membranes is critical to protecting metabolic activities and genetic information from the environment. Regulation of transport across membranes of essential chemicals, including water, nutrients, hormones and many drugs, is therefore key to cellular homeostasis and physiological processes. The two main transporter superfamilies are ATP-binding cassette (ABC) transporters that primarily function as efflux transporters, and the solute carrier (SLC) transporters. SLC transporters encompass 52 gene families with almost 400 different human transporter genes. Although long under-explored, SLC transporters are an emerging drug target class and the molecular target of several approved inhibitor drugs, such as selective serotonin reuptake inhibitors (SSRIs) for depression and sodium/glucose co-transporter (SGLT2) inhibitors for diabetes. Interestingly though, although loss-of-function mutations in numerous human SLC transporters are linked to Mendelian diseases, few reports of SLC transporter activators have appeared, and only inhibitors have been advanced to clinical studies. In this commentary, we discuss several strategies for potentiating SLC transporter function, from direct acting potentiators to modulators of transcription, translation or trafficking. We review the progress made in recent years toward the understanding of the structural and molecular basis of SLC transporter function and the pathways and mechanisms that regulate SLC expression, and describe the opportunities these new insights present for discovery of SLC transporter potentiators. Finally, we highlight the challenges associated with the various approaches and provide some thoughts on future directions that might facilitate the search for SLC potentiators with therapeutic potential.
[Mh] Termos MeSH primário: Descoberta de Drogas/métodos
Proteínas de Membrana Transportadoras/metabolismo
Proteínas Carreadoras de Solutos/metabolismo
[Mh] Termos MeSH secundário: Animais
Transporte Biológico/efeitos dos fármacos
Transporte Biológico/fisiologia
Membrana Celular/efeitos dos fármacos
Membrana Celular/metabolismo
Descoberta de Drogas/tendências
Seres Humanos
Proteínas de Membrana Transportadoras/química
Estrutura Secundária de Proteína
Estrutura Terciária de Proteína
Transporte Proteico/efeitos dos fármacos
Transporte Proteico/fisiologia
Inibidores da Captação de Serotonina/metabolismo
Inibidores da Captação de Serotonina/farmacologia
Proteínas Carreadoras de Solutos/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Membrane Transport Proteins); 0 (Serotonin Uptake Inhibitors); 0 (Solute Carrier Proteins)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170601
[Lr] Data última revisão:
170601
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170220
[St] Status:MEDLINE


  7 / 20 MEDLINE  
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[PMID]:28112518
[Au] Autor:Pelkonen L; Sato K; Reinisalo M; Kidron H; Tachikawa M; Watanabe M; Uchida Y; Urtti A; Terasaki T
[Ad] Endereço:School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland , 70210 Kuopio, Finland.
[Ti] Título:LC-MS/MS Based Quantitation of ABC and SLC Transporter Proteins in Plasma Membranes of Cultured Primary Human Retinal Pigment Epithelium Cells and Immortalized ARPE19 Cell Line.
[So] Source:Mol Pharm;14(3):605-613, 2017 Mar 06.
[Is] ISSN:1543-8392
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The retinal pigment epithelium (RPE) forms the outer blood-retinal barrier between neural retina and choroid. The RPE has several important vision supporting functions, such as transport mechanisms that may also modify pharmacokinetics in the posterior eye segment. Expression of plasma membrane transporters in the RPE cells has not been quantitated. The aim of this study was to characterize and compare transporter protein expression in the ARPE19 cell line and hfRPE (human fetal RPE) cells by using quantitative targeted absolute proteomics (QTAP). Among 41 studied transporters, 16 proteins were expressed in hfRPE and 13 in ARPE19 cells. MRP1, MRP5, GLUT1, 4F2hc, TAUT, CAT1, LAT1, and MATE1 proteins were detected in both cell lines within 4-fold differences. MPR7, OAT2 and RFC1 were detected in the hfRPE cells, but their expression levels were below the limit of quantification in ARPE19 cells. PCFT was detected in both studied cell lines, but the expression was over 4-fold higher in hfRPE cells. MCT1, MCT4, MRP4, and Na /K ATPase were upregulated in the ARPE19 cell line showing over 4-fold differences in the quantitative expression values. Expression levels of 25 transporters were below the limit of quantification in both cell models. In conclusion, we present the first systematic and quantitative study on transporter protein expression in the plasma membranes of ARPE19 and hfRPE cells. Overall, transporter expression in the ARPE19 and hfRPE cells correlated well and the absolute expression levels were similar, but not identical. The presented quantitative expression levels could be a useful basis for further studies on drug permeation in the outer blood-retinal barrier.
[Mh] Termos MeSH primário: Transportadores de Cassetes de Ligação de ATP/metabolismo
Membrana Celular/metabolismo
Epitélio Pigmentado Ocular/metabolismo
Epitélio Pigmentado da Retina/metabolismo
Proteínas Carreadoras de Solutos/metabolismo
[Mh] Termos MeSH secundário: Barreira Hematorretiniana/metabolismo
Proteínas de Transporte/metabolismo
Linhagem Celular
Cromatografia Líquida/métodos
Seres Humanos
Proteômica/métodos
ATPase Trocadora de Sódio-Potássio/metabolismo
Espectrometria de Massas em Tandem/métodos
Regulação para Cima/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carrier Proteins); 0 (Solute Carrier Proteins); EC 3.6.3.9 (Sodium-Potassium-Exchanging ATPase)
[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:170124
[St] Status:MEDLINE
[do] DOI:10.1021/acs.molpharmaceut.6b00782


  8 / 20 MEDLINE  
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[PMID]:28099443
[Au] Autor:Chedik L; Bruyere A; Le Vee M; Stieger B; Denizot C; Parmentier Y; Potin S; Fardel O
[Ad] Endereço:Institut de Recherches en Santé, Environnement et Travail (IRSET), UMR INSERM U1085, Faculté de Pharmacie, 2 Avenue du Pr Léon Bernard, Rennes, France.
[Ti] Título:Inhibition of Human Drug Transporter Activities by the Pyrethroid Pesticides Allethrin and Tetramethrin.
[So] Source:PLoS One;12(1):e0169480, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Pyrethroids are widely-used chemical insecticides, to which humans are commonly exposed, and known to alter functional expression of drug metabolizing enzymes. Limited data have additionally suggested that drug transporters, that constitute key-actors of the drug detoxification system, may also be targeted by pyrethroids. The present study was therefore designed to analyze the potential regulatory effects of these pesticides towards activities of main ATP-binding cassette (ABC) and solute carrier (SLC) drug transporters, using transporter-overexpressing cells. The pyrethroids allethrin and tetramethrin were found to inhibit various ABC and SLC drug transporters, including multidrug resistance-associated protein (MRP) 2, breast cancer resistance protein (BCRP), organic anion transporter polypeptide (OATP) 1B1, organic anion transporter (OAT) 3, multidrug and toxin extrusion transporter (MATE) 1, organic cation transporter (OCT) 1 and OCT2, with IC50 values however ranging from 2.6 µM (OCT1 inhibition by allethrin) to 77.6 µM (OAT3 inhibition by tetramethrin) and thus much higher than pyrethroid concentrations (in the nM range) reached in environmentally pyrethroid-exposed humans. By contrast, allethrin and tetramethrin cis-stimulated OATP2B1 activity and failed to alter activities of OATP1B3, OAT1 and MATE2-K, whereas P-glycoprotein activity was additionally moderately inhibited. Twelve other pyrethoids used at 100 µM did not block activities of the various investigated transporters, or only moderately inhibited some of them (inhibition by less than 50%). In silico analysis of structure-activity relationships next revealed that molecular parameters, including molecular weight and lipophilicity, are associated with transporter inhibition by allethrin/tetramethrin and successfully predicted transporter inhibition by the pyrethroids imiprothrin and prallethrin. Taken together, these data fully demonstrated that two pyrethoids, i.e., allethrin and tetramethrin, can act as regulators of the activity of various ABC and SLC drug transporters, but only when used at high and non-relevant concentrations, making unlikely any contribution of these transporter activity alterations to pyrethroid toxicity in environmentally exposed humans.
[Mh] Termos MeSH primário: Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores
Aletrina/toxicidade
Praguicidas/toxicidade
Piretrinas/toxicidade
Proteínas Carreadoras de Solutos/antagonistas & inibidores
[Mh] Termos MeSH secundário: Transportadores de Cassetes de Ligação de ATP/metabolismo
Aletrina/química
Linhagem Celular
Dopamina/metabolismo
Células HEK293/efeitos dos fármacos
Seres Humanos
Transportador 1 de Cátions Orgânicos/antagonistas & inibidores
Transportador 1 de Cátions Orgânicos/genética
Transportador 1 de Cátions Orgânicos/metabolismo
Praguicidas/química
Piretrinas/química
Proteínas Carreadoras de Solutos/metabolismo
Relação Estrutura-Atividade
Testes de Toxicidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Organic Cation Transporter 1); 0 (Pesticides); 0 (Pyrethrins); 0 (Solute Carrier Proteins); 0X03II877M (Allethrin); VTD58H1Z2X (Dopamine); Z72930Q46K (tetramethrin)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170816
[Lr] Data última revisão:
170816
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170119
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0169480


  9 / 20 MEDLINE  
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[PMID]:27939446
[Au] Autor:Perland E; Fredriksson R
[Ad] Endereço:Department of Pharmaceutical Bioscience, Molecular Neuropharmacology, Uppsala University, Uppsala SE 7512, Sweden.
[Ti] Título:Classification Systems of Secondary Active Transporters.
[So] Source:Trends Pharmacol Sci;38(3):305-315, 2017 Mar.
[Is] ISSN:1873-3735
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Membrane-bound solute carrier (SLC) transporter proteins are vital to the human body, as they sustain homeostasis by moving soluble molecule as nutrients, drugs, and waste across lipid membranes. Of the 430 identified secondary active transporters in humans, 30% are still orphans, and systematic research has been requested to elaborate on their possible involvement in diseases and their potential as drug targets. To enable this, the various classification systems in use must be understood and used correctly. In this review, we describe how various classification systems for human SLCs are constructed, and how they overlap and differ. To facilitate communication between researchers and to avoid ambiguities, everyone must clearly state which classification system they are referring to when writing scientific articles.
[Mh] Termos MeSH primário: Proteínas Carreadoras de Solutos/classificação
[Mh] Termos MeSH secundário: Transporte Biológico Ativo
Seres Humanos
Lipídeos de Membrana/metabolismo
Proteínas Carreadoras de Solutos/química
Proteínas Carreadoras de Solutos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Membrane Lipids); 0 (Solute Carrier Proteins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161213
[St] Status:MEDLINE


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[PMID]:27503090
[Au] Autor: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, 3 Pasteur Str., 02-093, Warsaw, Poland. k.nalecz@nencki.gov.pl.
[Ti] Título:Solute Carriers in the Blood-Brain Barier: Safety in Abundance.
[So] Source:Neurochem Res;42(3):795-809, 2017 Mar.
[Is] ISSN:1573-6903
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Blood-brain barrier formed by brain capillary endothelial cells, being in contact with astrocytes endfeet and pericytes, separates extracellular fluid from plasma. Supply of necessary nutrients and removal of certain metabolites takes place due to the activity of transporting proteins from ABC (ATP binding cassette) and SLC (solute carrier) superfamilies. This review is focused on the SLC families involved in transport though the blood-brain barrier of energetic substrates (glucose, monocarboxylates, creatine), amino acids, neurotransmitters and their precursors, as well as organic ions. Members of SLC1, SLC2, SLC3/SLC7, SLC5, SLC6, SLC16, SLC22, SLC38, SLC44, SLC47 and SLCO (SLC21), whose presence in the blood-brain barriers has been demonstrated are characterized with a special emphasis put on polarity of transporters localization in a luminal (blood side) versus an abluminal (brain side) membrane.
[Mh] Termos MeSH primário: Sistemas de Transporte de Aminoácidos/metabolismo
Barreira Hematoencefálica/metabolismo
Transportadores de Ânions Orgânicos/metabolismo
Proteínas de Transporte de Cátions Orgânicos/metabolismo
Proteínas Carreadoras de Solutos/metabolismo
[Mh] Termos MeSH secundário: Animais
Endotélio Vascular/metabolismo
Seres Humanos
Microvasos/metabolismo
Neurotransmissores/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Amino Acid Transport Systems); 0 (Neurotransmitter Agents); 0 (Organic Anion Transporters); 0 (Organic Cation Transport Proteins); 0 (Solute Carrier Proteins)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160810
[St] Status:MEDLINE
[do] DOI:10.1007/s11064-016-2030-x



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