Base de dados : MEDLINE
Pesquisa : D12.776.157.530.100.209 [Categoria DeCS]
Referências encontradas : 76 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 8 ir para página                    

  1 / 76 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28258215
[Au] Autor:Geillon F; Gondcaille C; Raas Q; Dias AMM; Pecqueur D; Truntzer C; Lucchi G; Ducoroy P; Falson P; Savary S; Trompier D
[Ad] Endereço:From the Laboratoire Bio-PeroxIL EA7270 and.
[Ti] Título:Peroxisomal ATP-binding cassette transporters form mainly tetramers.
[So] Source:J Biol Chem;292(17):6965-6977, 2017 Apr 28.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:ABCD1 and its homolog ABCD2 are peroxisomal ATP-binding cassette (ABC) half-transporters of fatty acyl-CoAs with both distinct and overlapping substrate specificities. Although it is established that ABC half-transporters have at least to dimerize to generate a functional unit, functional equivalents of tetramers ( dimers of full-length transporters) have also been reported. However, oligomerization of peroxisomal ABCD transporters is incompletely understood but is of potential significance because more complex oligomerization might lead to differences in substrate specificity. In this work, we have characterized the quaternary structure of the ABCD1 and ABCD2 proteins in the peroxisomal membrane. Using various biochemical approaches, we clearly demonstrate that both transporters exist as both homo- and heterotetramers, with a predominance of homotetramers. In addition to tetramers, some larger molecular ABCD assemblies were also found but represented only a minor fraction. By using quantitative co-immunoprecipitation assays coupled with tandem mass spectrometry, we identified potential binding partners of ABCD2 involved in polyunsaturated fatty-acid metabolism. Interestingly, we identified calcium ATPases as ABCD2-binding partners, suggesting a role of ABCD2 in calcium signaling. In conclusion, we have shown here that ABCD1 and its homolog ABCD2 exist mainly as homotetramers in the peroxisomal membrane.
[Mh] Termos MeSH primário: Transportadores de Cassetes de Ligação de ATP/metabolismo
Peroxissomos/metabolismo
[Mh] Termos MeSH secundário: Subfamília D de Transportador de Cassetes de Ligação de ATP
Membro 1 da Subfamília D de Transportadores de Cassetes de Ligação de ATP
Trifosfato de Adenosina/metabolismo
Animais
Células COS
Sinalização do Cálcio
ATPases Transportadoras de Cálcio/metabolismo
Carcinoma Hepatocelular/metabolismo
Linhagem Celular
Cercopithecus aethiops
Proteínas de Fluorescência Verde/metabolismo
Neoplasias Hepáticas/metabolismo
Espectrometria de Massas
Camundongos
Ligação Proteica
Mapeamento de Interação de Proteínas
Estrutura Quaternária de Proteína
Transporte Proteico
Ratos
Espectrometria de Massas em Tandem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ABCD1 protein, rat); 0 (ABCD2 protein, mouse); 0 (ATP Binding Cassette Transporter, Sub-Family D); 0 (ATP Binding Cassette Transporter, Sub-Family D, Member 1); 0 (Abcd1 protein, mouse); 0 (Abcd2 protein, rat); 147336-22-9 (Green Fluorescent Proteins); 8L70Q75FXE (Adenosine Triphosphate); EC 3.6.3.8 (Calcium-Transporting ATPases)
[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
[do] DOI:10.1074/jbc.M116.772806


  2 / 76 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28200172
[Au] Autor:Hartley MD; Kirkemo LL; Banerji T; Scanlan TS
[Ad] Endereço:Department of Physiology and Pharmacology and Program in Chemical Biology, Oregon Health & Science University, Portland, Oregon 92739.
[Ti] Título:A Thyroid Hormone-Based Strategy for Correcting the Biochemical Abnormality in X-Linked Adrenoleukodystrophy.
[So] Source:Endocrinology;158(5):1328-1338, 2017 May 01.
[Is] ISSN:1945-7170
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:X-linked adrenoleukodystrophy (X-ALD) is a rare, genetic disorder characterized by adrenal insufficiency and central nervous system (CNS) demyelination. All patients with X-ALD have the biochemical abnormality of elevated blood and tissue levels of very long chain fatty acids (VLCFAs), saturated fatty acids with 24 to 26 carbons. X-ALD results from loss of function mutations in the gene encoding the peroxisomal transporter ABCD1, which is responsible for uptake of VLCFAs into peroxisomes for degradation by oxidation. One proposed therapeutic strategy for genetic complementation of ABCD1 is pharmacologic upregulation of ABCD2, a gene encoding a homologous peroxisomal transporter. Here, we show that thyroid hormone or sobetirome, a clinical-stage selective thyroid hormone receptor agonist, increases cerebral Abcd2 and lowers VLCFAs in blood, peripheral organs, and brains of mice with defective Abcd1. These results support an approach to treating X-ALD that involves a thyromimetic agent that reactivates VLCFA disposal both in the periphery and the CNS.
[Mh] Termos MeSH primário: Transportadores de Cassetes de Ligação de ATP/genética
Transportadores de Cassetes de Ligação de ATP/metabolismo
Acetatos/uso terapêutico
Adrenoleucodistrofia/tratamento farmacológico
Adrenoleucodistrofia/metabolismo
Encéfalo/metabolismo
Fenóis/uso terapêutico
Hormônios Tireóideos/uso terapêutico
[Mh] Termos MeSH secundário: Subfamília D de Transportador de Cassetes de Ligação de ATP
Membro 1 da Subfamília D de Transportadores de Cassetes de Ligação de ATP
Transportadores de Cassetes de Ligação de ATP/deficiência
Acetatos/administração & dosagem
Adrenoleucodistrofia/sangue
Adrenoleucodistrofia/genética
Animais
Transporte Biológico
Linhagem Celular
Ácidos Graxos/sangue
Ácidos Graxos/metabolismo
Fibroblastos
Seres Humanos
Masculino
Camundongos
Peroxissomos/metabolismo
Fenóis/administração & dosagem
Receptores dos Hormônios Tireóideos/agonistas
Hormônios Tireóideos/administração & dosagem
Hormônios Tireóideos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ABCD2 protein, mouse); 0 (ATP Binding Cassette Transporter, Sub-Family D); 0 (ATP Binding Cassette Transporter, Sub-Family D, Member 1); 0 (Abcd1 protein, mouse); 0 (Acetates); 0 (Fatty Acids); 0 (GC 1 compound); 0 (Phenols); 0 (Receptors, Thyroid Hormone); 0 (Thyroid Hormones)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170216
[St] Status:MEDLINE
[do] DOI:10.1210/en.2016-1842


  3 / 76 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
[PMID]:27766264
[Au] Autor:Kawaguchi K; Morita M
[Ad] Endereço:Department of Biological Chemistry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
[Ti] Título:ABC Transporter Subfamily D: Distinct Differences in Behavior between ABCD1-3 and ABCD4 in Subcellular Localization, Function, and Human Disease.
[So] Source:Biomed Res Int;2016:6786245, 2016.
[Is] ISSN:2314-6141
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:ATP-binding cassette (ABC) transporters are one of the largest families of membrane-bound proteins and transport a wide variety of substrates across both extra- and intracellular membranes. They play a critical role in maintaining cellular homeostasis. To date, four ABC transporters belonging to subfamily D have been identified. ABCD1-3 and ABCD4 are localized to peroxisomes and lysosomes, respectively. ABCD1 and ABCD2 are involved in the transport of long and very long chain fatty acids (VLCFA) or their CoA-derivatives into peroxisomes with different substrate specificities, while ABCD3 is involved in the transport of branched chain acyl-CoA into peroxisomes. On the other hand, ABCD4 is deduced to take part in the transport of vitamin B from lysosomes into the cytosol. It is well known that the dysfunction of ABCD1 results in X-linked adrenoleukodystrophy, a severe neurodegenerative disease. Recently, it is reported that ABCD3 and ABCD4 are responsible for hepatosplenomegaly and vitamin B deficiency, respectively. In this review, the targeting mechanism and physiological functions of the ABCD transporters are summarized along with the related disease.
[Mh] Termos MeSH primário: Transportadores de Cassetes de Ligação de ATP/metabolismo
[Mh] Termos MeSH secundário: Subfamília D de Transportador de Cassetes de Ligação de ATP
Membro 1 da Subfamília D de Transportadores de Cassetes de Ligação de ATP
Transportadores de Cassetes de Ligação de ATP/genética
Adrenoleucodistrofia/genética
Adrenoleucodistrofia/metabolismo
Adrenoleucodistrofia/patologia
Ácidos Graxos/metabolismo
Seres Humanos
Lisossomos/genética
Lisossomos/metabolismo
Peroxissomos/genética
Peroxissomos/metabolismo
Especificidade por Substrato
Deficiência de Vitamina B 12/genética
Deficiência de Vitamina B 12/metabolismo
Deficiência de Vitamina B 12/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (ABCD1 protein, human); 0 (ABCD2 protein, human); 0 (ABCD3 protein, human); 0 (ABCD4 protein, human); 0 (ATP Binding Cassette Transporter, Sub-Family D); 0 (ATP Binding Cassette Transporter, Sub-Family D, Member 1); 0 (Fatty Acids)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161022
[St] Status:MEDLINE


  4 / 76 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26849413
[Au] Autor:Singh J; Olle B; Suhail H; Felicella MM; Giri S
[Ad] Endereço:Department of Neurology, Henry Ford Health System, Detroit, Michigan, USA.
[Ti] Título:Metformin-induced mitochondrial function and ABCD2 up-regulation in X-linked adrenoleukodystrophy involves AMP-activated protein kinase.
[So] Source:J Neurochem;138(1):86-100, 2016 Jul.
[Is] ISSN:1471-4159
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:X-linked adrenoleukodystrophy (X-ALD) is a progressive neurometabolic disease caused by mutations/deletions in the Abcd1 gene. Similar mutations/deletions in the Abcd1 gene often result in diagonally opposing phenotypes of mild adrenomyeloneuropathy and severe neuroinflammatory cerebral adrenoleukodystrophy (ALD), which suggests involvement of downstream modifier genes. We recently documented the first evidence of loss of AMP-activated protein kinase α1 (AMPKα1) in ALD patient-derived cells. Here, we report the novel loss of AMPKα1 in postmortem brain white matter of patients with ALD phenotype. Pharmacological activation of AMPK can rescue the mitochondrial dysfunction and inhibit the pro-inflammatory response. The FDA approved anti-diabetic drug Metformin, a well-known AMPK activator, induces mitochondrial biogenesis and is documented for its anti-inflammatory role. We observed a dose-dependent activation of AMPKα1 in metformin-treated X-ALD patient-derived fibroblasts. Metformin also induced mitochondrial oxidative phosphorylation and ATP levels in X-ALD patient-derived fibroblasts. Metformin treatment decreased very long chain fatty acid levels and pro-inflammatory cytokine gene expressions in X-ALD patient-derived cells. Abcd2 [adrenoleukodystrophy protein-related protein] levels were increased in metformin-treated X-ALD patient-derived fibroblasts and Abcd1-KO mice primary mixed glial cells. Abcd2 induction was AMPKα1-dependent since metformin failed to induce Abcd2 levels in AMPKα1-KO mice-derived primary mixed glial cells. In vivo metformin (100 mg/Kg) in drinking water for 60 days induced Abcd2 levels and mitochondrial oxidative phosphorylation protein levels in the brain and spinal cord of Abcd1-KO mice. Taken together, these results provide proof-of-principle for therapeutic potential of metformin as a useful strategy for correcting the metabolic and inflammatory derangements in X-ALD by targeting AMPK. There is no effective therapy for inherited peroxisomal disorder X-linked adrenoleukodystrophy (X-ALD). We document the therapeutic potential of FDA approved drug, Metformin, for X-ALD by targeting AMPK. Metformin induced peroxisomal Abcd2 levels in vitro and in vivo. Metformin lowered VLCFA levels, improved mitochondrial function and ameliorated inflammatory gene expression in X-ALD patient-derived cells. Metformin-induced Abcd2 levels were dependent on AMPKα1, a metabolic and anti-inflammatory gene, recently documented by our laboratory to play a putative role in X-ALD pathology. Read the Editorial Highlight for this article on page 10.
[Mh] Termos MeSH primário: Proteínas Quinases Ativadas por AMP/metabolismo
Transportadores de Cassetes de Ligação de ATP/metabolismo
Adrenoleucodistrofia/enzimologia
Adrenoleucodistrofia/patologia
Hipoglicemiantes/farmacologia
Metformina/farmacologia
Regulação para Cima/efeitos dos fármacos
[Mh] Termos MeSH secundário: Proteínas Quinases Ativadas por AMP/genética
Subfamília D de Transportador de Cassetes de Ligação de ATP
Membro 1 da Subfamília D de Transportadores de Cassetes de Ligação de ATP
Transportadores de Cassetes de Ligação de ATP/deficiência
Transportadores de Cassetes de Ligação de ATP/genética
Adrenoleucodistrofia/genética
Animais
Animais Recém-Nascidos
Encéfalo/metabolismo
Encéfalo/patologia
Modelos Animais de Doenças
Seres Humanos
Camundongos
Camundongos Knockout
Mitocôndrias/efeitos dos fármacos
Mitocôndrias/genética
Óxido Nítrico Sintase Tipo II/metabolismo
Oxirredução/efeitos dos fármacos
Consumo de Oxigênio/efeitos dos fármacos
Consumo de Oxigênio/genética
Fosforilação/efeitos dos fármacos
Fosforilação/genética
Fatores de Tempo
Regulação para Cima/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ABCD2 protein, human); 0 (ATP Binding Cassette Transporter, Sub-Family D); 0 (ATP Binding Cassette Transporter, Sub-Family D, Member 1); 0 (Abcd1 protein, mouse); 0 (Hypoglycemic Agents); 9100L32L2N (Metformin); EC 1.14.13.39 (Nitric Oxide Synthase Type II); EC 2.7.11.1 (AMPK alpha1 subunit, mouse); EC 2.7.11.31 (AMP-Activated Protein Kinases)
[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:160206
[St] Status:MEDLINE
[do] DOI:10.1111/jnc.13562


  5 / 76 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
[PMID]:26681085
[Au] Autor:Soucek P; Hlavac V; Elsnerova K; Vaclavikova R; Kozevnikovova R; Raus K
[Ad] Endereço:Biomedical Center, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen, Czech Republic. pavel.soucek@lfp.cuni.cz.
[Ti] Título:Whole exome sequencing analysis of ABCC8 and ABCD2 genes associating with clinical course of breast carcinoma.
[So] Source:Physiol Res;64 Suppl 4:S549-57, 2015.
[Is] ISSN:1802-9973
[Cp] País de publicação:Czech Republic
[La] Idioma:eng
[Ab] Resumo:The aim of the present study was to introduce methods for exome sequencing of two ATP-binding cassette (ABC) transporters ABCC8 and ABCD2 recently suggested to play a putative role in breast cancer progression and prognosis of patients. We performed next generation sequencing targeted at analysis of all exons in ABCC8 and ABCD2 genes and surrounding noncoding sequences in blood DNA samples from 24 patients with breast cancer. The revealed alterations were characterized by in silico tools. We then compared the most frequent functionally relevant polymorphism rs757110 in ABCC8 with clinical data of patients. In total, the study identified 113 genetic alterations (>70 % novel ones) in both genes. Of these alterations, 83 were noncoding, 13 synonymous, 10 frameshifts and 7 were missense alterations. Four in silico programs predicted pathogenicity of two polymorphisms and four newly identified alterations. Rs757110 polymorphism in ABCC8 did not significantly associate with clinical data of the patients. In conclusion, exome sequencing identified several functionally relevant alterations in ABCC8 and ABCD2 genes that may further be used for a larger follow-up study aiming to assess their clinical significance.
[Mh] Termos MeSH primário: Transportadores de Cassetes de Ligação de ATP/genética
Neoplasias da Mama/genética
Exoma/genética
Estudos de Associação Genética
Análise de Sequência de DNA
Receptores Sulfonilureia/genética
[Mh] Termos MeSH secundário: Subfamília D de Transportador de Cassetes de Ligação de ATP
Adulto
Neoplasias da Mama/diagnóstico
Feminino
Estudos de Associação Genética/métodos
Seres Humanos
Meia-Idade
Polimorfismo de Nucleotídeo Único/genética
Análise de Sequência de DNA/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (ABCC8 protein, human); 0 (ABCD2 protein, human); 0 (ATP Binding Cassette Transporter, Sub-Family D); 0 (Sulfonylurea Receptors)
[Em] Mês de entrada:1609
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151219
[St] Status:MEDLINE


  6 / 76 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:25604068
[Au] Autor:Li Q; Zhu X; Feng C; Fang M; Liu X
[Ad] Endereço:Department of Neurology, Shanghai Tenth People's Hospital of Tongji University, Shanghai, China (mainland).
[Ti] Título:Duration of symptom and ABCD2 score as predictors of risk of early recurrent events after transient ischemic attack: a hospital-based case series study.
[So] Source:Med Sci Monit;21:262-7, 2015 Jan 21.
[Is] ISSN:1643-3750
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The aim of this study was to refine clinical risk factor stratification and make an optimal intervention plan to prevent ischemic stroke. MATERIAL/METHODS: Clinical data, including diffusion-weighted imaging (DWI) findings, were collected in a cohort of hospitalized transient ischemic attack (TIA) patients from January 2010 to December 2011. Recurrent cerebrovascular events after TIA, including recurrent TIA, minor stroke, and major stroke, were identified by face-to-face follow-up. A multivariate, ordinal, logistic regression model was used to determine significant predictors of recurrent events. RESULTS: Of 106 TIA patients, 24 (22.6%) had recurrent TIA and 20 (18.9%) had a stroke within 7 days. Hypertension, dyslipidemia, a history of ischemic stroke or TIA, and ABCD2 score were significantly associated with the recurrent events after TIA (P<0.001, P=0.02, P<0.001, P=0.02). Hypertension (RR=9.21; 95% CI, 3.07-27.61, P<0.001) and duration of symptom (RR=1.10; 95% CI, 1.02-1.17, P=0.01) as an item of ABCD2 score were highly predictive of the severity of recurrent events, whereas ABCD2 score as a whole (P=0.18) proved to be less strongly predictive. CONCLUSIONS: A history of hypertension and long duration of symptom independently and significantly predict severe recurrent events after TIA within 7 days, but a high ABCD2 score was less strongly predictive of severe recurrent events.
[Mh] Termos MeSH primário: Transportadores de Cassetes de Ligação de ATP/metabolismo
Ataque Isquêmico Transitório/diagnóstico
Ataque Isquêmico Transitório/metabolismo
[Mh] Termos MeSH secundário: Subfamília D de Transportador de Cassetes de Ligação de ATP
Idoso
Estudos de Coortes
Imagem de Difusão por Ressonância Magnética
Feminino
Hospitalização
Hospitais
Seres Humanos
Hipertensão/complicações
Hipertensão/patologia
Ataque Isquêmico Transitório/terapia
Imagem por Ressonância Magnética
Masculino
Meia-Idade
Análise Multivariada
Valor Preditivo dos Testes
Recidiva
Medição de Risco
Fatores de Risco
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ABCD2 protein, human); 0 (ATP Binding Cassette Transporter, Sub-Family D)
[Em] Mês de entrada:1510
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150122
[St] Status:MEDLINE
[do] DOI:10.12659/MSM.892525


  7 / 76 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:25446110
[Au] Autor:Liu X; Liu J; Lester JD; Pijut SS; Graf GA
[Ad] Endereço:Department of Pharmaceutical Sciences, Saha Cardiovascular Research Center, Barnstable Brown Diabetes and Obesity Center, University of Kentucky, Lexington, KY, United States. Electronic address: xiaoxi.liu@uky.edu.
[Ti] Título:ABCD2 identifies a subclass of peroxisomes in mouse adipose tissue.
[So] Source:Biochem Biophys Res Commun;456(1):129-34, 2015 Jan 02.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:ATP-binding cassette transporter D2 (D2) is an ABC half transporter that is thought to promote the transport of very long-chain fatty acyl-CoAs into peroxisomes. Both D2 and peroxisomes increase during adipogenesis. Although peroxisomes are essential to both catabolic and anabolic lipid metabolism, their function, and that of D2, in adipose tissues remain largely unknown. Here, we investigated the D2 localization and the proteome of D2-containing organelles, in adipose tissue. Centrifugation of mouse adipose homogenates generated a fraction enriched with D2, but deficient in peroxisome markers including catalase, PEX19, and ABCD3 (D3). Electron microscopic imaging of this fraction confirmed the presence of D2 protein on an organelle with a dense matrix and a diameter of ∼ 200 nm, the typical structure and size of a microperoxisome. D2 and PEX19 antibodies recognized distinct structures in mouse adipose. Immunoisolation of the D2-containing compartment confirmed the scarcity of PEX19 and proteomic profiling revealed the presence of proteins associated with peroxisome, endoplasmic reticulum (ER), and mitochondria. D2 is localized to a distinct class of peroxisomes that lack many peroxisome proteins, and may associate physically with mitochondria and the ER.
[Mh] Termos MeSH primário: Transportadores de Cassetes de Ligação de ATP/metabolismo
Tecido Adiposo/metabolismo
Peroxissomos/metabolismo
[Mh] Termos MeSH secundário: Subfamília D de Transportador de Cassetes de Ligação de ATP
Animais
Retículo Endoplasmático/metabolismo
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Microscopia Eletrônica
Microscopia de Fluorescência
Mitocôndrias/metabolismo
Proteoma/metabolismo
Proteômica
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (ABCD2 protein, mouse); 0 (ATP Binding Cassette Transporter, Sub-Family D); 0 (Proteome)
[Em] Mês de entrada:1503
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:141203
[St] Status:MEDLINE


  8 / 76 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:25255441
[Au] Autor:Muneer Z; Wiesinger C; Voigtländer T; Werner HB; Berger J; Forss-Petter S
[Ad] Endereço:Center for Brain Research, Medical University of Vienna, Vienna, Austria.
[Ti] Título:Abcd2 is a strong modifier of the metabolic impairments in peritoneal macrophages of ABCD1-deficient mice.
[So] Source:PLoS One;9(9):e108655, 2014.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The inherited peroxisomal disorder X-linked adrenoleukodystrophy (X-ALD), associated with neurodegeneration and inflammatory cerebral demyelination, is caused by mutations in the ABCD1 gene encoding the peroxisomal ATP-binding cassette (ABC) transporter ABCD1 (ALDP). ABCD1 transports CoA-esters of very long-chain fatty acids (VLCFA) into peroxisomes for degradation by ß-oxidation; thus, ABCD1 deficiency results in VLCFA accumulation. The closest homologue, ABCD2 (ALDRP), when overexpressed, compensates for ABCD1 deficiency in X-ALD fibroblasts and in Abcd1-deficient mice. Microglia/macrophages have emerged as important players in the progression of neuroinflammation. Human monocytes, lacking significant expression of ABCD2, display severely impaired VLCFA metabolism in X-ALD. Here, we used thioglycollate-elicited primary mouse peritoneal macrophages (MPMΦ) from Abcd1 and Abcd2 single- and double-deficient mice to establish how these mutations affect VLCFA metabolism. By quantitative RT-PCR, Abcd2 mRNA was about half as abundant as Abcd1 mRNA in wild-type and similarly abundant in Abcd1-deficient MPMΦ. VLCFA (C26∶0) accumulated about twofold in Abcd1-deficient MPMΦ compared with wild-type controls, as measured by gas chromatography-mass spectrometry. In Abcd2-deficient macrophages VLCFA levels were normal. However, upon Abcd1/Abcd2 double-deficiency, VLCFA accumulation was markedly increased (sixfold) compared with Abcd1-deficient MPMΦ. Elovl1 mRNA, encoding the rate-limiting enzyme for elongation of VLCFA, was equally abundant across all genotypes. Peroxisomal ß-oxidation of C26∶0 amounted to 62% of wild-type activity in Abcd1-deficient MPMΦ and was significantly more impaired (29% residual activity) upon Abcd1/Abcd2 double-deficiency. Single Abcd2 deficiency did not significantly compromise ß-oxidation of C26∶0. Thus, the striking accumulation of VLCFA in double-deficient MPMΦ compared with single Abcd1 deficiency was due to the loss of ABCD2-mediated, compensatory transport of VLCFA into peroxisomes. We propose that moderate endogenous expression of Abcd2 in Abcd1-deficient murine macrophages prevents the severe metabolic phenotype observed in human X-ALD monocytes, which lack appreciable expression of ABCD2. This supports upregulation of ABCD2 as a therapeutic concept in X-ALD.
[Mh] Termos MeSH primário: Transportadores de Cassetes de Ligação de ATP/deficiência
Transportadores de Cassetes de Ligação de ATP/genética
Transportadores de Cassetes de Ligação de ATP/metabolismo
Macrófagos Peritoneais/metabolismo
[Mh] Termos MeSH secundário: Subfamília D de Transportador de Cassetes de Ligação de ATP
Membro 1 da Subfamília D de Transportadores de Cassetes de Ligação de ATP
Acetiltransferases/genética
Acetiltransferases/metabolismo
Animais
Coenzima A Ligases/metabolismo
Ácidos Graxos/metabolismo
Regulação da Expressão Gênica
Ordem dos Genes
Inativação Gênica
Marcação de Genes
Vetores Genéticos/genética
Metabolismo dos Lipídeos
Masculino
Camundongos
Camundongos Knockout
Oxirredução
Peroxissomos/metabolismo
RNA Mensageiro/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (ABCD2 protein, mouse); 0 (ATP Binding Cassette Transporter, Sub-Family D); 0 (ATP Binding Cassette Transporter, Sub-Family D, Member 1); 0 (Abcd1 protein, mouse); 0 (Fatty Acids); 0 (RNA, Messenger); EC 2.3.1.- (Acetyltransferases); EC 2.3.1.- (fatty acid elongases); EC 6.2.1.- (Coenzyme A Ligases); EC 6.2.1.3 (long-chain-fatty-acid-CoA ligase)
[Em] Mês de entrada:1512
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140926
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0108655


  9 / 76 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:25123288
[Au] Autor:Liu X; Liu J; Liang S; Schlüter A; Fourcade S; Aslibekyan S; Pujol A; Graf GA
[Ad] Endereço:Department of Pharmaceutical Sciences, Saha Cardiovascular Research Center, and Barnstable Brown Diabetes and Obesity Center, University of Kentucky, Lexington, Kentucky (X.L., J.L., S.L., G.A.G.); Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute, L'Hospitalet de Llobregat
[Ti] Título:ABCD2 alters peroxisome proliferator-activated receptor α signaling in vitro, but does not impair responses to fenofibrate therapy in a mouse model of diet-induced obesity.
[So] Source:Mol Pharmacol;86(5):505-13, 2014 Nov.
[Is] ISSN:1521-0111
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Fenofibrate is a peroxisome proliferator-activated receptor (PPAR) α ligand that has been widely used as a lipid-lowering agent in the treatment of hypertriglyceridemia. ABCD2 (D2) is a peroxisomal long-chain acyl-CoA transporter that is highly induced by fenofibrate in the livers of mice. To determine whether D2 is a modifier of fibrate responses, wild-type and D2-deficient mice were treated with fenofibrate for 14 days. The absence of D2 altered expression of gene clusters associated with lipid metabolism, including PPARα signaling. Using 3T3-L1 adipocytes, which express high levels of D2, we confirmed that knockdown of D2 modified genomic responses to fibrate treatment. We next evaluated the impact of D2 on effects of fibrates in a mouse model of diet-induced obesity. Fenofibrate treatment opposed the development of obesity, hypertriglyceridemia, and insulin resistance. However, these effects were unaffected by D2 genotype. We concluded that D2 can modulate genomic responses to fibrates, but that these effects are not sufficiently robust to alter the effects of fibrates on diet-induced obesity phenotypes.
[Mh] Termos MeSH primário: Transportadores de Cassetes de Ligação de ATP/genética
Transportadores de Cassetes de Ligação de ATP/metabolismo
Fenofibrato/farmacologia
Obesidade/tratamento farmacológico
PPAR alfa/genética
PPAR alfa/metabolismo
[Mh] Termos MeSH secundário: Subfamília D de Transportador de Cassetes de Ligação de ATP
Adipócitos/efeitos dos fármacos
Adipócitos/metabolismo
Animais
Dieta/métodos
Modelos Animais de Doenças
Hipertrigliceridemia/tratamento farmacológico
Hipertrigliceridemia/genética
Resistência à Insulina/genética
Metabolismo dos Lipídeos/efeitos dos fármacos
Metabolismo dos Lipídeos/genética
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Obesidade/genética
Obesidade/metabolismo
Transdução de Sinais/efeitos dos fármacos
Transdução de Sinais/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (ABCD2 protein, mouse); 0 (ATP Binding Cassette Transporter, Sub-Family D); 0 (PPAR alpha); U202363UOS (Fenofibrate)
[Em] Mês de entrada:1501
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140816
[St] Status:MEDLINE
[do] DOI:10.1124/mol.114.092742


  10 / 76 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:25079382
[Au] Autor:Weber FD; Weinhofer I; Einwich A; Forss-Petter S; Muneer Z; Maier H; Weber WH; Berger J
[Ad] Endereço:Center for Brain Research, Medical University of Vienna, Vienna, Austria.
[Ti] Título:Evaluation of retinoids for induction of the redundant gene ABCD2 as an alternative treatment option in X-linked adrenoleukodystrophy.
[So] Source:PLoS One;9(7):e103742, 2014.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:X-linked adrenoleukodystrophy (X-ALD), the most common peroxisomal disorder, is a clinically heterogeneous disease that can manifest as devastating inflammatory cerebral demyelination (CALD) leading to death of affected males. Currently, the only curative treatment is allogeneic hematopoietic stem cell transplantation (HSCT). However, HSCT is only effective when performed at an early stage because the inflammation may progress for eighteen months after HSCT. Thus, alternative treatment options able to immediately halt the progression are urgently needed. X-ALD is caused by mutations in the ABCD1 gene, encoding the peroxisomal membrane protein ABCD1, resulting in impaired very long-chain fatty acid metabolism. The related ABCD2 protein is able to functionally compensate for ABCD1-deficiency both in vitro and in vivo. Recently, we demonstrated that of the cell types derived from CD34+ stem cells, predominantly monocytes but not lymphocytes are metabolically impaired in X-ALD. As ABCD2 is virtually not expressed in these cells, we hypothesize that a pharmacological up-regulation of ABCD2 should compensate metabolically and halt the inflammation in CALD. Retinoids are anti-inflammatory compounds known to act on ABCD2. Here, we investigated the capacity of selected retinoids for ABCD2 induction in human monocytes/macrophages. In THP-1 cells, 13-cis-retinoic acid reached the highest, fivefold, increase in ABCD2 expression. To test the efficacy of retinoids in vivo, we analyzed ABCD2 mRNA levels in blood cells isolated from acne patients receiving 13-cis-retinoic acid therapy. In treated acne patients, ABCD2 mRNA levels were comparable to pre-treatment levels in monocytes and lymphocytes. Nevertheless, when primary monocytes were in vitro differentiated into macrophages and treated with 13-cis-retinoic acid, we observed a fourfold induction of ABCD2. However, the level of ABCD2 induction obtained by retinoids alone is probably not of therapeutic relevance for X-ALD. In conclusion, our results suggest a change in promoter accessibility during macrophage differentiation allowing induction of ABCD2 by retinoids.
[Mh] Termos MeSH primário: Transportadores de Cassetes de Ligação de ATP/genética
Adrenoleucodistrofia/tratamento farmacológico
Retinoides/farmacologia
Ativação Transcricional/efeitos dos fármacos
[Mh] Termos MeSH secundário: Subfamília D de Transportador de Cassetes de Ligação de ATP
Transportadores de Cassetes de Ligação de ATP/metabolismo
Acne Vulgar/genética
Acne Vulgar/imunologia
Acne Vulgar/metabolismo
Adolescente
Adrenoleucodistrofia/genética
Adrenoleucodistrofia/metabolismo
Adulto
Estudos de Casos e Controles
Linhagem Celular
Expressão Gênica
Seres Humanos
Macrófagos/efeitos dos fármacos
Macrófagos/metabolismo
Masculino
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (ABCD2 protein, human); 0 (ATP Binding Cassette Transporter, Sub-Family D); 0 (Retinoids)
[Em] Mês de entrada:1511
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140801
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0103742



página 1 de 8 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