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[PMID]:28510245
[Au] Autor:Zhang H; Shi WJ
[Ad] Endereço:Department of Neurosurgery, , , China.
[Ti] Título:Association of three common single nucleotide polymorphisms of SLC7A7 with the development of glioma in a Chinese population.
[So] Source:Genet Mol Res;16(2), 2017 May 10.
[Is] ISSN:1676-5680
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:Gliomas are brain tumors that can be seriously damaging to human health. The SLC7 family is involved in amino acid or peptide transportation. The relationship between SLC7A7 polymorphisms and the development of glioma has been reported previously by a few studies. Therefore, we performed a hospital based case-control study to investigate the association of three common SNPs (rs12888930, rs12436190, and rs2065134) of SLC7A7 with the development of glioma in a Chinese population. From January 2014 to December 2015, 122 patients with glioma and 252 individuals (controls) were recruited from the department of neurosurgery of Tangshan People's Hospital affiliated to North China University of Science and Technology. SLC7A7 rs12888930, rs12436190, and rs2065134 genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism method. Multiple logistic regression analysis showed that a significantly higher risk of glioma was harbored by the GG and AG + GG genotypes than by the AA genotype; OR (95%CI) was 2.24 (1.18-4.22) and 1.59 (1.01-2.60), respectively. However, no significant relationship was observed between SLC7A7 rs12888930 and rs2065134 and the risk of glioma. In conclusion, this study reports a significant association between SLC7A7 rs12436190 and the risk of glioma in a Chinese population.
[Mh] Termos MeSH primário: Neoplasias Encefálicas/genética
Cadeias Leves da Proteína-1 Reguladora de Fusão/genética
Glioma/genética
Polimorfismo de Nucleotídeo Único
[Mh] Termos MeSH secundário: Estudos de Casos e Controles
China
Feminino
Seres Humanos
Masculino
Meia-Idade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fusion Regulatory Protein 1, Light Chains); 0 (SLC7A7 protein, human)
[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:170517
[St] Status:MEDLINE
[do] DOI:10.4238/gmr16029026


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[PMID]:28087478
[Au] Autor:Estève E; Krug P; Hummel A; Arnoux JB; Boyer O; Brassier A; de Lonlay P; Vuiblet V; Gobin S; Salomon R; Piètrement C; Bonnefont JP; Servais A; Galmiche L
[Ad] Endereço:Pathology Department Hôpital Necker-Enfants Malades, Assistance Publique, Hôpitaux de Paris, Université Sorbonne Paris Cité, 75015, Paris, France. Electronic address: esteve.emmanuel@gmail.com.
[Ti] Título:Renal involvement in lysinuric protein intolerance: contribution of pathology to assessment of heterogeneity of renal lesions.
[So] Source:Hum Pathol;62:160-169, 2017 Apr.
[Is] ISSN:1532-8392
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Lysinuric protein intolerance (LPI) is a rare autosomal recessive disease caused by mutations in the SLC7A7 gene encoding the light subunit of a cationic amino acid transporter. Symptoms mimic primary urea cycle defects but dysimmune symptoms are also described. Renal involvement in LPI was first described in the 1980s. In 2007, it appeared that it could concern as much as 75% of LPI patients and could lead to end-stage renal disease. The most common feature is proximal tubular dysfunction and nephrocalcinosis but glomerular lesions are also reported. However, very little is known regarding histological lesions associated with LPI. We gathered every kidney biopsy of LPI-proven patients in our highly specialized pediatric and adult institution. Clinical, biological, and histological information was analyzed. Five LPI patients underwent kidney biopsy in our institution between 1986 and 2015. Clinically, 4/5 presented with proximal tubular dysfunction and 3/5 with nephrotic range proteinuria. Histology showed unspecific tubulointerstitial lesions and nephrocalcinosis in 3/5 biopsies and marked peritubular capillaritis in one child. Glomerular lesions were heterogeneous: lupus-like-full house membranoproliferative glomerulonephritis (MPGN) in one child evolved towards monotypic IgG1κ MPGN sensitive to immunomodulators. One patient presented with glomerular non-AA non-AL amyloidosis. Renal biopsy is particularly relevant in LPI presenting with glomerular symptoms for which variable histological lesions can be responsible, implying specific treatment and follow-up.
[Mh] Termos MeSH primário: Erros Inatos do Metabolismo dos Aminoácidos/patologia
Rim/patologia
[Mh] Termos MeSH secundário: Adolescente
Adulto
Erros Inatos do Metabolismo dos Aminoácidos/complicações
Erros Inatos do Metabolismo dos Aminoácidos/genética
Erros Inatos do Metabolismo dos Aminoácidos/terapia
Amiloidose/etiologia
Amiloidose/patologia
Biópsia
Criança
Progressão da Doença
Feminino
Imunofluorescência
Cadeias Leves da Proteína-1 Reguladora de Fusão/genética
Predisposição Genética para Doença
Glomerulonefrite Membranoproliferativa/etiologia
Glomerulonefrite Membranoproliferativa/patologia
Seres Humanos
Lactente
Masculino
Mutação
Nefrocalcinose/etiologia
Nefrocalcinose/patologia
Síndrome Nefrótica/etiologia
Síndrome Nefrótica/patologia
Paris
Fenótipo
Proteinúria/etiologia
Proteinúria/patologia
Insuficiência Renal Crônica/etiologia
Insuficiência Renal Crônica/patologia
Fatores de Tempo
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fusion Regulatory Protein 1, Light Chains); 0 (SLC7A7 protein, human)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170115
[St] Status:MEDLINE


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[PMID]:28028301
[Au] Autor:Habib A; Azize NA; Yakob Y; Md Yunus Z; Wee TK
[Ad] Endereço:Institute for Medical Research, Specialised Diagnostic Centre, Biochemistry Unit, Jalan Pahang 50588 Kuala Lumpur, Malaysia. anasufiza@imr.gov.my.
[Ti] Título:Biochemical and molecular characteristics of Malaysian patients with lysinuric protein intolerance.
[So] Source:Malays J Pathol;38(3):305-310, 2016 Dec.
[Is] ISSN:0126-8635
[Cp] País de publicação:Malaysia
[La] Idioma:eng
[Ab] Resumo:Lysinuric protein intolerance (LPI) is an inborn error of dibasic amino acid transport due to a defect in the dibasic amino acid transporter in the renal and intestine and has a heterogenous presentation. Three Malaysian patients with LPI were studied and their biochemical and molecular findings compared. There were differences and similarities in the biochemical and molecular findings. Molecular analysis of SLC7A7 gene revealed a novel mutation c.235G>A; p.(Gly79Arg) in exon three in Patient 1 and a mutation c.1417C>T; p.(Arg473*) in exon 10 in patient 2 and 3. The degree of concentration of dibasic amino acids may determine the type of disease of the cell membrane transport, however, a positive molecular confirmation will secure the diagnosis.
[Mh] Termos MeSH primário: Erros Inatos do Metabolismo dos Aminoácidos/genética
Cadeias Leves da Proteína-1 Reguladora de Fusão/genética
[Mh] Termos MeSH secundário: Pré-Escolar
Análise Mutacional de DNA
Feminino
Seres Humanos
Lactente
Malásia
Masculino
Mutação
Reação em Cadeia da Polimerase
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fusion Regulatory Protein 1, Light Chains); 0 (SLC7A7 protein, human)
[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:161229
[St] Status:MEDLINE


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[PMID]:27494059
[Au] Autor:Ganguly A; Touma M; Thamotharan S; De Vivo DC; Devaskar SU
[Ad] Endereço:Department of Pediatrics (A.G., M.T., S.T., S.U.D.), Division of Neonatology and Developmental Biology, and Neonatal Research Center at the UCLA Children's Discovery and Innovation Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095; and D
[Ti] Título:Maternal Calorie Restriction Causing Uteroplacental Insufficiency Differentially Affects Mammalian Placental Glucose and Leucine Transport Molecular Mechanisms.
[So] Source:Endocrinology;157(10):4041-4054, 2016 Oct.
[Is] ISSN:1945-7170
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We examined the effect of mild (Mi; ∼25%) and moderate (Mo; ∼50%) maternal calorie restriction (MCR) vs ad libitum-fed controls on placental glucose and leucine transport impacting fetal growth potential. We observed in MiMCR a compensatory increase in transplacental (TP) glucose transport due to increased placental glucose transporter isoform (GLUT)-3 but no change in GLUT1 protein concentrations. This change was paralleled by increased glut3 mRNA and 5-hydroxymethylated cytosines with enhanced recruitment of histone 3 lysine demethylase to the glut3 gene locus. To assess the biologic relevance of placental GLUT1, we also examined glut1 heterozygous null vs wild-type mice and observed no difference in placental GLUT3 and TP or intraplacental glucose and leucine transport. Both MCR states led to a graded decrease in TP and intraplacental leucine transport, with a decline in placental L amino acid transporter isoform 2 (LAT2) concentrations and increased microRNA-149 (targets LAT2) and microRNA-122 (targets GLUT3) expression in MoMCR alone. These changes were accompanied by a step-wise reduction in uterine and umbilical artery Doppler blood flow with decreased fetal left ventricular ejection fraction and fractional shortening. We conclude that MiMCR transactivates placental GLUT3 toward preserving TP glucose transport in the face of reduced leucine transport. This contrasts MoMCR in which a reduction in placental GLUT3 mediated glucose transport with a reciprocal increase in miR-122 expression was encountered. A posttranscriptional reduction in LAT2-mediated leucine transport also occurred with enhanced miR-149 expression. Both MCR states, although not affecting placental GLUT1, resulted in uteroplacental insufficiency and fetal growth restriction with compromised cardiovascular health.
[Mh] Termos MeSH primário: Restrição Calórica/efeitos adversos
Placenta/metabolismo
Insuficiência Placentária/etiologia
Fenômenos Fisiológicos da Nutrição Pré-Natal
[Mh] Termos MeSH secundário: Sistema y+ de Transporte de Aminoácidos/metabolismo
Animais
Desenvolvimento Embrionário
Feminino
Retardo do Crescimento Fetal/etiologia
Retardo do Crescimento Fetal/metabolismo
Cadeias Leves da Proteína-1 Reguladora de Fusão/metabolismo
Glucose/metabolismo
Transportador de Glucose Tipo 1/metabolismo
Transportador de Glucose Tipo 3/metabolismo
Leucina/metabolismo
Camundongos Endogâmicos C57BL
Placenta/patologia
Circulação Placentária
Insuficiência Placentária/metabolismo
Gravidez
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acid Transport System y+); 0 (Fusion Regulatory Protein 1, Light Chains); 0 (Glucose Transporter Type 1); 0 (Glucose Transporter Type 3); 0 (SLC7A8 protein, mouse); 0 (Slc2a1 protein, mouse); 0 (Slc2a3 protein, mouse); GMW67QNF9C (Leucine); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:160806
[St] Status:MEDLINE


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[PMID]:27321952
[Au] Autor:Ghilain V; Wiame E; Fomekong E; Vincent MF; Dumitriu D; Nassogne MC
[Ad] Endereço:Université Catholique de Louvain and Cliniques Universitaires Saint-Luc, Brussels, Belgium.
[Ti] Título:Unusual association between lysinuric protein intolerance and moyamoya vasculopathy.
[So] Source:Eur J Paediatr Neurol;20(5):777-81, 2016 Sep.
[Is] ISSN:1532-2130
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Lysinuric protein intolerance (LPI) is a form of inherited aminoaciduria caused by a deficiency in the cationic amino acid transport process on the basolateral membrane of enterocytes and renal tubular cells. Clinical signs include gastrointestinal symptoms, failure to thrive, hepatosplenomegaly, osteoporosis, episodes of coma, intellectual deficiency, lung and renal involvement, bone marrow abnormalities, as well as altered immune response. Moyamoya disease is a cerebrovascular disorder predisposing sufferers to stroke through progressive stenosis of the intracranial internal carotid arteries and their proximal branches. Patients with characteristic moyamoya vasculopathy who also exhibit well-recognized associated conditions, such as Down syndrome or sickle-cell disease, are diagnosed with moyamoya syndrome, whereas those with no known associated risk factors are said to suffer from moyamoya disease. CASE STUDY: A 5-year-old girl exhibiting aversion to protein-rich food and splenomegaly presented with a history of recurrent ischemic strokes. Cerebral angiography confirmed moyamoya vasculopathy. Metabolic investigation revealed abnormalities characteristic of LPI. This diagnosis was confirmed by the detection of a mutation within the SLC7A7 gene upon molecular investigation. CONCLUSION: To the best of our knowledge, this is the first reported case of an association between moyamoya vasculopathy and LPI. While the question of association or coincidence cannot yet be answered, several pathophysiological consequences of LPI can be defined as separate, such as links between the impact of low arginine levels on the function of vascular endothelium and brain nitric oxide metabolism, as well as hemophagocytic syndrome associated with the risk of vasculitis, thus accounting for the development of moyamoya vasculopathy.
[Mh] Termos MeSH primário: Erros Inatos do Metabolismo dos Aminoácidos/complicações
Doença de Moyamoya/complicações
[Mh] Termos MeSH secundário: Erros Inatos do Metabolismo dos Aminoácidos/genética
Pré-Escolar
Feminino
Cadeias Leves da Proteína-1 Reguladora de Fusão/genética
Seres Humanos
Mutação
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fusion Regulatory Protein 1, Light Chains); 0 (SLC7A7 protein, human)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160621
[St] Status:MEDLINE


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[PMID]:27105919
[Au] Autor:Asaoka Y; Nagai Y; Namae M; Furutani-Seiki M; Nishina H
[Ad] Endereço:Department of Developmental and Regenerative Biology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
[Ti] Título:SLC7 family transporters control the establishment of left-right asymmetry during organogenesis in medaka by activating mTOR signaling.
[So] Source:Biochem Biophys Res Commun;474(1):146-153, 2016 05 20.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The precise government of the left-right (LR) specification of an organ is an essential aspect of its morphogenesis. Multiple signaling cascades have been implicated in the establishment of vertebrate LR asymmetry. Recently, mTOR signaling was found to critically regulate the development of LR asymmetry in zebrafish. However, the upstream factor(s) that activate mTOR signaling in the context of LR specification are as yet unknown. In this study, we identify the SLC7 amino acid transporters Slc7a7 and Slc7a8 as novel regulators of LR asymmetry development in the small fish medaka. Knockdown of Slc7a7 and/or Slc7a8 in medaka embryos disrupted LR organ asymmetries. Depletion of Slc7a7 hindered left-sided expression of the southpaw (spaw) gene, which is responsible for LR axis determination. Work at the cellular level revealed that Slc7a7 coordinates ciliogenesis in the epithelium of Kupffer's vesicle and thereby the generation of the nodal fluid flow required for LR asymmetry. Interestingly, knockdown of Slc7a7 depressed mTOR signaling activity in medaka embryos. Treatment with rapamycin, an inhibitor of mTOR signaling, together with Slc7a7 knockdown synergistically perturbed spaw expression, indicating an interaction between Slc7a7 and mTOR signaling affecting gene expression required for LR specification. Taken together, our results demonstrate that Slc7a7 governs the regulation of LR asymmetry development via the activation of mTOR signaling.
[Mh] Termos MeSH primário: Padronização Corporal/fisiologia
Cadeias Leves da Proteína-1 Reguladora de Fusão/metabolismo
Organogênese/fisiologia
Oryzias/fisiologia
Serina-Treonina Quinases TOR/metabolismo
[Mh] Termos MeSH secundário: Animais
Regulação da Expressão Gênica no Desenvolvimento/fisiologia
Transdução de Sinais/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Fusion Regulatory Protein 1, Light Chains); 0 (SLC7A7 protein, human); EC 2.7.1.1 (TOR Serine-Threonine Kinases)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171117
[Lr] Data última revisão:
171117
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160424
[St] Status:MEDLINE


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[PMID]:26945935
[Au] Autor:de la Ballina LR; Cano-Crespo S; González-Muñoz E; Bial S; Estrach S; Cailleteau L; Tissot F; Daniel H; Zorzano A; Ginsberg MH; Palacín M; Féral CC
[Ad] Endereço:From the Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology, Baldiri Reixac 10, 08028 Barcelona, Spain and Department of Biochemistry and Molecular Biology, University of Barcelona, 08028 Barcelona, Spain, INSERM, U1081, Institute for Research on Can
[Ti] Título:Amino Acid Transport Associated to Cluster of Differentiation 98 Heavy Chain (CD98hc) Is at the Cross-road of Oxidative Stress and Amino Acid Availability.
[So] Source:J Biol Chem;291(18):9700-11, 2016 Apr 29.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:CD98hc functions as an amino acid (AA) transporter (together with another subunit) and integrin signaling enhancer. It is overexpressed in highly proliferative cells in both physiological and pathological conditions. CD98hc deletion induces strong impairment of cell proliferation in vivo and in vitro Here, we investigate CD98hc-associated AA transport in cell survival and proliferation. By using chimeric versions of CD98hc, the two functions of the protein can be uncoupled. Although recovering the CD98hc AA transport capacity restores the in vivo and in vitro proliferation of CD98hc-null cells, reconstitution of the integrin signaling function of CD98hc is unable to restore in vitro proliferation of those cells. CD98hc-associated transporters (i.e. xCT, LAT1, and y(+)LAT2 in wild-type cells) are crucial to control reactive oxygen species and intracellular AA levels, thus sustaining cell survival and proliferation. Moreover, in CD98hc-null cells the deficiency of CD98hc/xCT cannot be compensated, leading to cell death by ferroptosis. Supplementation of culture media with ß-mercaptoethanol rescues CD98hc-deficient cell survival. Under such conditions null cells show oxidative stress and intracellular AA imbalance and, consequently, limited proliferation. CD98hc-null cells also present reduced intracellular levels of branched-chain and aromatic amino acids (BCAAs and ARO AAs, respectively) and induced expression of peptide transporter 1 (PEPT1). Interestingly, external supply of dipeptides containing BCAAs and ARO AAs rescues cell proliferation and compensates for impaired uptake of CD98hc/LAT1 and CD98hc/y(+)LAT2. Our data establish CD98hc as a master protective gene at the cross-road of redox control and AA availability, making it a relevant therapeutic target in cancer.
[Mh] Termos MeSH primário: Aminoácidos/metabolismo
Diferenciação Celular/fisiologia
Proliferação Celular/fisiologia
Cadeia Pesada da Proteína-1 Reguladora de Fusão/metabolismo
Células-Tronco Embrionárias Murinas/metabolismo
Estresse Oxidativo
[Mh] Termos MeSH secundário: Sistema y+ de Transporte de Aminoácidos/genética
Sistema y+ de Transporte de Aminoácidos/metabolismo
Aminoácidos/genética
Animais
Transporte Biológico Ativo/fisiologia
Linhagem Celular
Sobrevivência Celular/fisiologia
Cadeia Pesada da Proteína-1 Reguladora de Fusão/genética
Cadeias Leves da Proteína-1 Reguladora de Fusão/genética
Cadeias Leves da Proteína-1 Reguladora de Fusão/metabolismo
Deleção de Genes
Camundongos
Células-Tronco Embrionárias Murinas/citologia
Espécies Reativas de Oxigênio/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Amino Acid Transport System y+); 0 (Amino Acids); 0 (Fusion Regulatory Protein 1, Heavy Chain); 0 (Fusion Regulatory Protein 1, Light Chains); 0 (Reactive Oxygen Species); 0 (SLC7A8 protein, mouse); 0 (Slc7a7 protein, mouse)
[Em] Mês de entrada:1611
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160307
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M115.704254


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[PMID]:26740192
[Au] Autor:Straka E; Ellinger I; Balthasar C; Scheinast M; Schatz J; Szattler T; Bleichert S; Saleh L; Knöfler M; Zeisler H; Hengstschläger M; Rosner M; Salzer H; Gundacker C
[Ad] Endereço:Institute of Medical Genetics, Medical University Vienna, Vienna, Austria.
[Ti] Título:Mercury toxicokinetics of the healthy human term placenta involve amino acid transporters and ABC transporters.
[So] Source:Toxicology;340:34-42, 2016 Jan 18.
[Is] ISSN:1879-3185
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The capacity of the human placenta to handle exogenous stressors is poorly understood. The heavy metal mercury is well-known to pass the placenta and to affect brain development. An active transport across the placenta has been assumed. The underlying mechanisms however are virtually unknown. OBJECTIVES: Uptake and efflux transporters (17 candidate proteins) assumed to play a key role in placental mercury transfer were examined for expression, localization and function in human primary trophoblast cells and the trophoblast-derived choriocarcinoma cell line BeWo. METHODS: To prove involvement of the transporters, we used small interfering RNA (siRNA) and exposed cells to methylmercury (MeHg). Total mercury contents of cells were analyzed by Cold vapor-atomic fluorescence spectrometry (CV-AFS). Localization of the proteins in human term placenta sections was determined via immunofluorescence microscopy. RESULTS: We found the amino acid transporter subunits L-type amino acid transporter (LAT)1 and rBAT (related to b(0,+) type amino acid transporter) as well as the efflux transporter multidrug resistance associated protein (MRP)1 to be involved in mercury kinetics of trophoblast cells (t-test P<0.05). CONCLUSION: The amino acid transporters located at the apical side of the syncytiotrophoblast (STB) manage uptake of MeHg. Mercury conjugated to glutathione (GSH) is effluxed via MRP1 localized to the basal side of the STB. The findings can well explain why mercury is transported primarily towards the fetal side.
[Mh] Termos MeSH primário: Transportadores de Cassetes de Ligação de ATP/metabolismo
Sistemas de Transporte de Aminoácidos/metabolismo
Compostos de Metilmercúrio/metabolismo
Compostos de Metilmercúrio/toxicidade
Placenta/metabolismo
[Mh] Termos MeSH secundário: Transportadores de Cassetes de Ligação de ATP/genética
Sistemas de Transporte de Aminoácidos/genética
Sistemas de Transporte de Aminoácidos Básicos/metabolismo
Sistemas de Transporte de Aminoácidos Neutros/metabolismo
Transporte Biológico
Linhagem Celular Tumoral
Coriocarcinoma/genética
Coriocarcinoma/metabolismo
Feminino
Cadeias Leves da Proteína-1 Reguladora de Fusão/metabolismo
Seres Humanos
Cinética
Compostos de Metilmercúrio/administração & dosagem
Microscopia de Fluorescência
Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo
Gravidez
Interferência de RNA
Espectrometria de Fluorescência
Transfecção
Trofoblastos/metabolismo
Neoplasias Uterinas/genética
Neoplasias Uterinas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Amino Acid Transport Systems); 0 (Amino Acid Transport Systems, Basic); 0 (Amino Acid Transport Systems, Neutral); 0 (Fusion Regulatory Protein 1, Light Chains); 0 (Methylmercury Compounds); 0 (Multidrug Resistance-Associated Proteins); 0 (SLC3A1 protein, human); 0 (SLC7A7 protein, human); Y49M64GZ4Q (multidrug resistance-associated protein 1)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160108
[St] Status:MEDLINE


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[PMID]:26661195
[Au] Autor:Dolgodilina E; Imobersteg S; Laczko E; Welt T; Verrey F; Makrides V
[Ad] Endereço:Institute of Physiology, Zurich Center for Integrative Human Physiology (ZIHP) and NCCR Kidney. CH, University of Zurich, Zurich, Switzerland.
[Ti] Título:Brain interstitial fluid glutamine homeostasis is controlled by blood-brain barrier SLC7A5/LAT1 amino acid transporter.
[So] Source:J Cereb Blood Flow Metab;36(11):1929-1941, 2016 Nov.
[Is] ISSN:1559-7016
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:L-glutamine (Gln) is the most abundant amino acid in plasma and cerebrospinal fluid and a precursor for the main central nervous system excitatory (L-glutamate) and inhibitory (γ-aminobutyric acid (GABA)) neurotransmitters. Concentrations of Gln and 13 other brain interstitial fluid amino acids were measured in awake, freely moving mice by hippocampal microdialysis using an extrapolation to zero flow rate method. Interstitial fluid levels for all amino acids including Gln were ∼5-10 times lower than in cerebrospinal fluid. Although the large increase in plasma Gln by intraperitoneal (IP) injection of N -labeled Gln (hGln) did not increase total interstitial fluid Gln, low levels of hGln were detected in microdialysis samples. Competitive inhibition of system A (SLC38A1&2; SNAT1&2) or system L (SLC7A5&8; LAT1&2) transporters in brain by perfusion with α-(methylamino)-isobutyric acid (MeAIB) or 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) respectively, was tested. The data showed a significantly greater increase in interstitial fluid Gln upon BCH than MeAIB treatment. Furthermore, brain BCH perfusion also strongly increased the influx of hGln into interstitial fluid following IP injection consistent with transstimulation of LAT1-mediated transendothelial transport. Taken together, the data support the independent homeostatic regulation of amino acids in interstitial fluid vs. cerebrospinal fluid and the role of the blood-brain barrier expressed SLC7A5/LAT1 as a key interstitial fluid gatekeeper.
[Mh] Termos MeSH primário: Barreira Hematoencefálica/metabolismo
Líquido Extracelular/metabolismo
Glutamina/metabolismo
Homeostase
Transportador 1 de Aminoácidos Neutros Grandes/metabolismo
[Mh] Termos MeSH secundário: Sistema A de Transporte de Aminoácidos/metabolismo
Sistema y+ de Transporte de Aminoácidos/metabolismo
Aminoácidos Cíclicos/farmacologia
Animais
Cadeias Leves da Proteína-1 Reguladora de Fusão/metabolismo
Hipocampo/metabolismo
Masculino
Camundongos Endogâmicos C57BL
Microdiálise
beta-Alanina/análogos & derivados
beta-Alanina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acid Transport System A); 0 (Amino Acid Transport System y+); 0 (Amino Acids, Cyclic); 0 (Fusion Regulatory Protein 1, Light Chains); 0 (Large Neutral Amino Acid-Transporter 1); 0 (SLC7A8 protein, mouse); 0 (Slc38a1 protein, mouse); 0 (Slc38a2 protein, mouse); 0RH81L854J (Glutamine); 11P2JDE17B (beta-Alanine); 19036-43-2 (2,2-dimethyl-beta-alanine); 20448-79-7 (2-aminobicyclo(2,2,1)heptane-2-carboxylic acid)
[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:151215
[St] Status:MEDLINE


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[PMID]:26608079
[Au] Autor:Rosario FJ; Dimasuay KG; Kanai Y; Powell TL; Jansson T
[Ad] Endereço:Division of Reproductive Sciences, Department of OB/GYN, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, U.S.A. fredrick.joseph@ucdenver.edu.
[Ti] Título:Regulation of amino acid transporter trafficking by mTORC1 in primary human trophoblast cells is mediated by the ubiquitin ligase Nedd4-2.
[So] Source:Clin Sci (Lond);130(7):499-512, 2016 Apr 01.
[Is] ISSN:1470-8736
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Changes in placental amino acid transfer directly contribute to altered fetal growth, which increases the risk for perinatal complications and predisposes for the development of obesity, diabetes and cardiovascular disease later in life. Placental amino acid transfer is critically dependent on the expression of specific transporters in the plasma membrane of the trophoblast, the transporting epithelium of the human placenta. However, the molecular mechanisms regulating this process are largely unknown. Nedd4-2 is an ubiquitin ligase that catalyses the ubiquitination of proteins, resulting in proteasomal degradation. We hypothesized that inhibition of mechanistic target of rapamycin complex 1 (mTORC1) decreases amino acid uptake in primary human trophoblast (PHT) cells by activation of Nedd4-2, which increases transporter ubiquitination resulting in decreased transporter expression in the plasma membrane. mTORC 1 inhibition increased the expression of Nedd4-2, promoted ubiquitination and decreased the plasma membrane expression of SNAT2 (an isoform of the System A amino acid transporter) and LAT1 (a System L amino acid transporter isoform), resulting in decreased cellular amino acid uptake. Nedd4-2 silencing markedly increased the trafficking of SNAT2 and LAT1 to the plasma membrane, which stimulated cellular amino acid uptake. mTORC1 inhibition by silencing of raptor failed to decrease amino acid transport following Nedd4-2 silencing. In conclusion, we have identified a novel link between mTORC1 signalling and ubiquitination, a common posttranslational modification. Because placental mTORC1 is inhibited in fetal growth restriction and activated in fetal overgrowth, we propose that regulation of placental amino acid transporter ubiquitination by mTORC1 and Nedd4-2 constitutes a molecular mechanisms underlying abnormal fetal growth.
[Mh] Termos MeSH primário: Proteínas Adaptadoras de Transdução de Sinal/metabolismo
Sistema A de Transporte de Aminoácidos/metabolismo
Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo
Cadeias Leves da Proteína-1 Reguladora de Fusão/metabolismo
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
Complexos Multiproteicos/metabolismo
Serina-Treonina Quinases TOR/metabolismo
Trofoblastos/enzimologia
Ubiquitina-Proteína Ligases/metabolismo
[Mh] Termos MeSH secundário: Proteínas Adaptadoras de Transdução de Sinal/genética
Células Cultivadas
Complexos Endossomais de Distribuição Requeridos para Transporte/genética
Feminino
Seres Humanos
Peptídeos e Proteínas de Sinalização Intracelular/genética
Alvo Mecanístico do Complexo 1 de Rapamicina
Alvo Mecanístico do Complexo 2 de Rapamicina
Complexos Multiproteicos/genética
Ubiquitina-Proteína Ligases Nedd4
Gravidez
Cultura Primária de Células
Transporte Proteico
Interferência de RNA
Proteína Associada Regulatória a mTOR
Transdução de Sinais
Serina-Treonina Quinases TOR/genética
Transfecção
Ubiquitina-Proteína Ligases/genética
Ubiquitinação
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Adaptor Proteins, Signal Transducing); 0 (Amino Acid Transport System A); 0 (Endosomal Sorting Complexes Required for Transport); 0 (Fusion Regulatory Protein 1, Light Chains); 0 (Intracellular Signaling Peptides and Proteins); 0 (Multiprotein Complexes); 0 (RPTOR protein, human); 0 (Regulatory-Associated Protein of mTOR); 0 (SLC38A1 protein, human); 0 (SLC7A7 protein, human); EC 2.3.2.26 (Nedd4 Ubiquitin Protein Ligases); EC 2.3.2.26 (Nedd4 protein, human); EC 2.3.2.26 (Nedd4L protein, human); EC 2.3.2.27 (Ubiquitin-Protein Ligases); EC 2.7.1.1 (DEPTOR protein, human); EC 2.7.1.1 (TOR Serine-Threonine Kinases); EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1); EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2)
[Em] Mês de entrada:1606
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151127
[St] Status:MEDLINE
[do] DOI:10.1042/CS20150554



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