Base de dados : MEDLINE
Pesquisa : D12.776.260.531 [Categoria DeCS]
Referências encontradas : 2309 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 231 ir para página                         

  1 / 2309 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29233651
[Au] Autor:Gong H; Weinstein DS; Lu Z; Duan JJ; Stachura S; Haque L; Karmakar A; Hemagiri H; Raut DK; Gupta AK; Khan J; Camac D; Sack JS; Pudzianowski A; Wu DR; Yarde M; Shen DR; Borowski V; Xie JH; Sun H; D'Arienzo C; Dabros M; Galella MA; Wang F; Weigelt CA; Zhao Q; Foster W; Somerville JE; Salter-Cid LM; Barrish JC; Carter PH; Dhar TGM
[Ad] Endereço:Bristol-Myers Squibb, Research and Development, Princeton, NJ 08543-4000, United States.
[Ti] Título:Identification of bicyclic hexafluoroisopropyl alcohol sulfonamides as retinoic acid receptor-related orphan receptor gamma (RORγ/RORc) inverse agonists. Employing structure-based drug design to improve pregnane X receptor (PXR) selectivity.
[So] Source:Bioorg Med Chem Lett;28(2):85-93, 2018 01 15.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:We disclose the optimization of a high throughput screening hit to yield benzothiazine and tetrahydroquinoline sulfonamides as potent RORγt inverse agonists. However, a majority of these compounds showed potent activity against pregnane X receptor (PXR) and modest activity against liver X receptor α (LXRα). Structure-based drug design (SBDD) led to the identification of benzothiazine and tetrahydroquinoline sulfonamide analogs which completely dialed out LXRα activity and were less potent at PXR. Pharmacodynamic (PD) data for compound 35 in an IL-23 induced IL-17 mouse model is discussed along with the implications of a high Y in the PXR assay for long term preclinical pharmacokinetic (PK) studies.
[Mh] Termos MeSH primário: Compostos Bicíclicos com Pontes/farmacologia
Desenho de Drogas
Propanóis/farmacologia
Receptores do Ácido Retinoico/agonistas
Receptores de Esteroides/agonistas
Sulfonamidas/farmacologia
[Mh] Termos MeSH secundário: Animais
Compostos Bicíclicos com Pontes/síntese química
Compostos Bicíclicos com Pontes/química
Cristalografia por Raios X
Relação Dose-Resposta a Droga
Seres Humanos
Receptores X do Fígado/agonistas
Masculino
Camundongos
Camundongos Endogâmicos BALB C
Modelos Moleculares
Estrutura Molecular
Propanóis/síntese química
Propanóis/química
Relação Estrutura-Atividade
Sulfonamidas/síntese química
Sulfonamidas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bridged Bicyclo Compounds); 0 (Liver X Receptors); 0 (Propanols); 0 (Receptors, Retinoic Acid); 0 (Receptors, Steroid); 0 (Sulfonamides); 0 (pregnane X receptor); 0 (retinoic acid receptor gamma); 3D632GYQ50 (hexafluoroisopropanol)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171214
[St] Status:MEDLINE


  2 / 2309 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28449117
[Au] Autor:Maczewsky J; Sikimic J; Bauer C; Krippeit-Drews P; Wolke C; Lendeckel U; Barthlen W; Drews G
[Ad] Endereço:Institute of Pharmacy, Department of Pharmacology, University of Tübingen, 72076 Tübingen, Germany.
[Ti] Título:The LXR Ligand T0901317 Acutely Inhibits Insulin Secretion by Affecting Mitochondrial Metabolism.
[So] Source:Endocrinology;158(7):2145-2154, 2017 07 01.
[Is] ISSN:1945-7170
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The role of liver X receptor (LXR) in pancreatic ß-cell physiology and pathophysiology is still unclear. It has been postulated that chronic LXR activation in ß-cells induces lipotoxicity, a key step in the development of ß-cell dysfunction, which accompanies type 2 diabetes mellitus. In most of these studies, the LXR ligand T0901317 has been administered chronically in the micromolar range to study the significance of LXR activation. In the current study, we have evaluated acute effects of T0901317 on stimulus-secretion coupling of ß-cells. We found that 10 µM T0901317 completely suppressed oscillations of the cytosolic Ca2+ concentration induced by 15 mM glucose. Obviously, this effect was due to inhibition of mitochondrial metabolism. T0901317 markedly depolarized the mitochondrial membrane potential, thus inhibiting adenosine triphosphate (ATP) production and reducing the cytosolic ATP concentration. This led in turn to a huge increase in KATP current and hyperpolarization of the cell membrane potential. Eventually, T0901317 inhibited glucose-induced insulin secretion. These effects were rapid in on-set and not compatible with the activation of a nuclear receptor. In vivo, T0901317 acutely increased the blood glucose concentration after intraperitoneal application. In summary, these data clearly demonstrate that T0901317 exerts acute effects on stimulus-secretion coupling. This observation questions the chronic use of T0901317 and limits the interpretation of results obtained under these experimental conditions.
[Mh] Termos MeSH primário: Hidrocarbonetos Fluorados/farmacologia
Células Secretoras de Insulina/efeitos dos fármacos
Insulina/secreção
Receptores X do Fígado/agonistas
Mitocôndrias/efeitos dos fármacos
Sulfonamidas/farmacologia
[Mh] Termos MeSH secundário: Animais
Feminino
Células Secretoras de Insulina/secreção
Células Secretoras de Insulina/ultraestrutura
Ligantes
Receptores X do Fígado/genética
Masculino
Potencial da Membrana Mitocondrial/efeitos dos fármacos
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Mitocôndrias/metabolismo
Espécies Reativas de Oxigênio/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Hydrocarbons, Fluorinated); 0 (Insulin); 0 (Ligands); 0 (Liver X Receptors); 0 (Reactive Oxygen Species); 0 (Sulfonamides); 0 (TO-901317)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180203
[Lr] Data última revisão:
180203
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170428
[St] Status:MEDLINE
[do] DOI:10.1210/en.2016-1941


  3 / 2309 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29185131
[Au] Autor:Alshammari GM; Balakrishnan A; Chinnasamy T
[Ad] Endereço:Department of Food Science and Nutrition, College of Food and Agricultural Science, King Saud University, P.O. Box 2460, Riyadh, 11451, Saudi Arabia. ghedeirksu@gmail.com.
[Ti] Título:Nimbolide attenuate the lipid accumulation, oxidative stress and antioxidant in primary hepatocytes.
[So] Source:Mol Biol Rep;44(6):463-474, 2017 Dec.
[Is] ISSN:1573-4978
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Nimbolide is a bioactive compound found in Azadirachta indica. This work was devised to investigate the potential effects of nimbolide on intracellular lipid deposition and its associated redox modulation in primary hepatocytes (Heps). Lipid accumulation was induced in Heps by supplementing 1 mM oleic acid for 24 h which was marked by significant accumulation of lipids. The results demonstrated that nimbolide can decrease intracellular cholesterol, free fatty acids and triglycerides. Nimbolide may also improve hepatocytes function through its antioxidant effects by inhibiting oxidative DNA damage and lipid peroxidation by curtailing the reactive oxygen species levels. Further it also restore the mitochondrial potential, improving the endogenous antioxidant levels such as GSH and antioxidant enzyme activities. Nimbolide increased (P < 0.05) liver X receptor-α (LXRα), peroxisome proliferator-activated receptor-γ (PPARγ) and sterol regulatory element-binding protein-1c (SREBP1c) gene expression in Heps. The biological significance of nimbolide may involve hypolipidemic effect, lipid peroxidation inhibition, DNA damage inhibition, ROS inhibition, restoring mitochondrial function, increases in GSH and SOD & CAT activities, and direct regulation of LXRα, PPARγ and SREBP1c gene expression. Nimbolide may be used as effective lipid lowering compound and lipid deposition-induced Heps changes.
[Mh] Termos MeSH primário: Hepatócitos/efeitos dos fármacos
Hepatócitos/metabolismo
Limoninas/farmacologia
Metabolismo dos Lipídeos/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Antioxidantes/farmacologia
Células Cultivadas
Seres Humanos
Hipolipemiantes/farmacologia
Peroxidação de Lipídeos/efeitos dos fármacos
Receptores X do Fígado/metabolismo
Oxirredução/efeitos dos fármacos
Estresse Oxidativo/efeitos dos fármacos
PPAR gama/metabolismo
Espécies Reativas de Oxigênio/metabolismo
Triglicerídeos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antioxidants); 0 (Hypolipidemic Agents); 0 (Limonins); 0 (Liver X Receptors); 0 (PPAR gamma); 0 (Reactive Oxygen Species); 0 (Triglycerides); 25990-37-8 (nimbolide)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180102
[Lr] Data última revisão:
180102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171130
[St] Status:MEDLINE
[do] DOI:10.1007/s11033-017-4132-1


  4 / 2309 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29173234
[Au] Autor:López-Oliva ME; Garcimartin A; Muñoz-Martínez E
[Ad] Endereço:1Sección Departamental de Fisiología, Facultad de Farmacia,Universidad Complutense de Madrid,28040 Madrid,Spain.
[Ti] Título:Dietary α-lactalbumin induced fatty liver by enhancing nuclear liver X receptor αß/sterol regulatory element-binding protein-1c/PPARγ expression and minimising PPARα/carnitine palmitoyltransferase-1 expression and AMP-activated protein kinase α phosphorylation associated with atherogenic dyslipidaemia, insulin resistance and oxidative stress in Balb/c mice.
[So] Source:Br J Nutr;118(11):914-929, 2017 Dec.
[Is] ISSN:1475-2662
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The effect and the role played by dietary α-lactalbumin (α-LAC) on hepatic fat metabolism are yet to be fully elucidated. We reported previously that α-LAC intake induced atherogenic dyslipidaemia in Balb/c mice. The aim of the present study was to investigate if this atherogenic effect could be due to a possible α-LAC-induced hepatic steatosis. We examine the ability of dietary α-LAC to induce liver steatosis, identifying the molecular mechanisms underlying hepatic lipid metabolism in association with the lipid profile, peripheral insulin resistance (IR) and changes in the hepatic oxidative environment. Male Balb/c mice (n 6) were fed with diets containing either chow or 14 % α-LAC for 4 weeks. The α-LAC-fed mice developed abdominal adiposity and IR. Moderate liver steatosis with increased TAG and NEFA contents was correlated with atherogenic dyslipidaemia. There was increased nuclear expression of liver X receptor αß (LXRαß), sterol regulatory element-binding protein-1c (SREBP-1c) and PPARγ transcription factors and of the cytosolic enzymes acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase involved in the hepatic de novo lipogenesis. The opposite was found for the nuclear receptor PPARα and the mitochondrial enzyme carnitine palmitoyltransferase-1 (CPT-1), leading to reduced fatty acid ß-oxidation (FAO). These changes were associated with a significant decrease in both p-Thr172-AMP-activated protein kinase α (AMPKα) (inactivation) and p-Ser79-ACC1 (activation) and with a more oxidative liver environment increasing lipid peroxidation and protein oxidation and reducing GSH:GSSG ratio in the α-LAC-fed mice. In conclusion, 4 weeks of 14 % α-LAC feeding induced liver steatosis associated with atherogenic dyslipidaemia, IR and oxidative stress by enhancing nuclear LXRαß/SREBP-1c/PPARγ expression and diminishing PPARα/CPT-1 expression and AMPKα phosphorylation shifting the hepatic FAO toward fatty acid synthesis in Balb/c mice.
[Mh] Termos MeSH primário: Carnitina O-Palmitoiltransferase/metabolismo
Fígado Gorduroso/metabolismo
Receptores X do Fígado/metabolismo
PPAR alfa/metabolismo
PPAR gama/metabolismo
Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
[Mh] Termos MeSH secundário: Proteínas Quinases Ativadas por AMP/genética
Proteínas Quinases Ativadas por AMP/metabolismo
Acetil-CoA Carboxilase/genética
Acetil-CoA Carboxilase/metabolismo
Animais
Aterosclerose/diagnóstico
Aterosclerose/etiologia
Aterosclerose/genética
Carnitina O-Palmitoiltransferase/genética
Dislipidemias/diagnóstico
Dislipidemias/etiologia
Dislipidemias/genética
Fígado Gorduroso/induzido quimicamente
Fígado Gorduroso/genética
Resistência à Insulina
Lactalbumina/efeitos adversos
Peroxidação de Lipídeos/efeitos dos fármacos
Fígado/efeitos dos fármacos
Fígado/metabolismo
Receptores X do Fígado/genética
Masculino
Camundongos
Camundongos Endogâmicos BALB C
Estresse Oxidativo
PPAR alfa/genética
PPAR gama/genética
Fosforilação
Proteína de Ligação a Elemento Regulador de Esterol 1/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Liver X Receptors); 0 (PPAR alpha); 0 (PPAR gamma); 0 (Srebf1 protein, mouse); 0 (Sterol Regulatory Element Binding Protein 1); 9013-90-5 (Lactalbumin); EC 2.3.1.21 (CPT1B protein, mouse); EC 2.3.1.21 (Carnitine O-Palmitoyltransferase); EC 2.7.11.31 (AMP-Activated Protein Kinases); EC 6.4.1.2 (ACC1 protein, mouse); EC 6.4.1.2 (Acetyl-CoA Carboxylase)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171218
[Lr] Data última revisão:
171218
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1017/S000711451700232X


  5 / 2309 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
[PMID]:28982861
[Au] Autor:Bobin-Dubigeon C; Chauvin A; Brillaud-Meflah V; Boiffard F; Joalland MP; Bard JM
[Ad] Endereço:Department of Biopathology, Institute of Cancer and Oncology, Saint-Herblain, France.
[Ti] Título:Liver X Receptor (LXR)-regulated Genes of Cholesterol Trafficking and Breast Cancer Severity.
[So] Source:Anticancer Res;37(10):5495-5498, 2017 10.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Liver X receptor [LXR; nuclear receptor subfamily 1, group H, member 2 (NR1H2, alias LXRB)] can inhibit proliferation and induce apoptosis of cancer cells. Its relationship with disease severity is not known. MATERIALS AND METHODS: Expression of LXRB, ATP binding cassette subfamily A member 1 (ABCA1), ATP binding cassette subfamily G member 1 (ABCG1), apolipoprotein E (APOE) and paraoxonase 2 (PON2) were determined in 69 breast tumors and were related to clinical stages of the disease and tumor characteristics, as well as time to recurrence. RESULTS: ABCG1 expression differed with the tumor Scarff Bloom and Richardson (SBR) status (p=0.02), with a lower expression in SBRIII than in SBRII and SBRI. ABCG1 expression was significantly higher in estrogen receptor-positive tumors (N=63) (p=0.02). APOE expression was significantly lower in progesterone receptor-positive tumors (N=55) (p=0.03). No relationship with time to recurrence was observed. CONCLUSION: Expression of some LXR-dependent genes is related to breast tumor characteristics, but not time to recurrence. This may be due to a lack of study power or too short a follow-up time.
[Mh] Termos MeSH primário: Neoplasias da Mama/genética
Colesterol/metabolismo
Receptores X do Fígado/genética
[Mh] Termos MeSH secundário: Transportador 1 de Cassete de Ligação de ATP/genética
Transportador 1 de Cassete de Ligação de ATP/metabolismo
Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética
Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo
Adulto
Idoso
Idoso de 80 Anos ou mais
Apolipoproteínas E/genética
Apolipoproteínas E/metabolismo
Arildialquilfosfatase/genética
Arildialquilfosfatase/metabolismo
Neoplasias da Mama/metabolismo
Neoplasias da Mama/patologia
Neoplasias da Mama/terapia
Intervalo Livre de Doença
Feminino
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Estimativa de Kaplan-Meier
Receptores X do Fígado/metabolismo
Meia-Idade
Recidiva Local de Neoplasia
Estadiamento de Neoplasias
Estudos Retrospectivos
Fatores de Tempo
Resultado do Tratamento
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ABCA1 protein, human); 0 (ABCG1 protein, human); 0 (ATP Binding Cassette Transporter 1); 0 (ATP Binding Cassette Transporter, Sub-Family G, Member 1); 0 (ApoE protein, human); 0 (Apolipoproteins E); 0 (Liver X Receptors); 0 (NR1H2 protein, human); 97C5T2UQ7J (Cholesterol); EC 3.1.8.1 (Aryldialkylphosphatase); EC 3.1.8.1 (PON2 protein, human)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171007
[St] Status:MEDLINE


  6 / 2309 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28926619
[Au] Autor:Herold M; Breuer J; Hucke S; Knolle P; Schwab N; Wiendl H; Klotz L
[Ad] Endereço:Department of Neurology, University of Muenster, Albert-Schweitzer-Campus 1, Muenster, Germany.
[Ti] Título:Liver X receptor activation promotes differentiation of regulatory T cells.
[So] Source:PLoS One;12(9):e0184985, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The nuclear receptor Liver X Receptor (LXR) is a ligand-activated transcription factor that has been implicated in control of chronic inflammation by downregulating pro-inflammatory T cell responses. An impaired function of regulatory T cells, a subset of CD4+ T cells with a crucial role in maintaining lymphocytes homeostasis and immune regulation, is frequently observed in chronic inflammatory diseases. We observed that pharmacological activation of LXR in T cells not only resulted in a thorough suppression of Th1 and Th17 polarization in vitro, but also significantly induced regulatory T cells (Treg) cell differentiation in a receptor-specific fashion. In line with this, systemic LXR activation by oral treatment of mice with the LXR agonist GW3965 induced gut-associated regulatory T cells in vivo. Importantly, such LXR-activated Tregs had a higher suppressive capacity in functional in vitro coculture assays with effector T cells. Our data thus point towards a dual role of LXR-mediated control of inflammation by suppression of pro-inflammatory T cells and reciprocal induction of regulatory T cells.
[Mh] Termos MeSH primário: Receptores X do Fígado/metabolismo
Linfócitos T Reguladores/metabolismo
[Mh] Termos MeSH secundário: Administração Oral
Animais
Benzoatos/farmacologia
Benzilaminas/farmacologia
Linfócitos T CD4-Positivos/citologia
Linfócitos T CD4-Positivos/metabolismo
Diferenciação Celular/efeitos dos fármacos
Técnicas de Cocultura
Citocinas/análise
Ensaio de Imunoadsorção Enzimática
Intestinos/imunologia
Intestinos/metabolismo
Receptores X do Fígado/agonistas
Receptores X do Fígado/genética
Linfonodos/efeitos dos fármacos
Linfonodos/imunologia
Camundongos
Camundongos Knockout
Linfócitos T Reguladores/citologia
Linfócitos T Reguladores/efeitos dos fármacos
Células Th1/citologia
Células Th1/efeitos dos fármacos
Células Th1/imunologia
Células Th17/citologia
Células Th17/efeitos dos fármacos
Células Th17/imunologia
Fator de Crescimento Transformador beta/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzoates); 0 (Benzylamines); 0 (Cytokines); 0 (GW 3965); 0 (Liver X Receptors); 0 (Transforming Growth Factor beta)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171020
[Lr] Data última revisão:
171020
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170920
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184985


  7 / 2309 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28846071
[Au] Autor:Rong X; Wang B; Palladino EN; de Aguiar Vallim TQ; Ford DA; Tontonoz P
[Ad] Endereço:Department of Pathology and Laboratory Medicine, Department of Medicine, UCLA, Los Angeles, California, USA.
[Ti] Título:ER phospholipid composition modulates lipogenesis during feeding and in obesity.
[So] Source:J Clin Invest;127(10):3640-3651, 2017 Oct 02.
[Is] ISSN:1558-8238
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Sterol regulatory element-binding protein 1c (SREBP-1c) is a central regulator of lipogenesis whose activity is controlled by proteolytic cleavage. The metabolic factors that affect its processing are incompletely understood. Here, we show that dynamic changes in the acyl chain composition of ER phospholipids affect SREBP-1c maturation in physiology and disease. The abundance of polyunsaturated phosphatidylcholine in liver ER is selectively increased in response to feeding and in the setting of obesity-linked insulin resistance. Exogenous delivery of polyunsaturated phosphatidylcholine to ER accelerated SREBP-1c processing through a mechanism that required an intact SREBP cleavage-activating protein (SCAP) pathway. Furthermore, induction of the phospholipid-remodeling enzyme LPCAT3 in response to liver X receptor (LXR) activation promoted SREBP-1c processing by driving the incorporation of polyunsaturated fatty acids into ER. Conversely, LPCAT3 deficiency increased membrane saturation, reduced nuclear SREBP-1c abundance, and blunted the lipogenic response to feeding, LXR agonist treatment, or obesity-linked insulin resistance. Desaturation of the ER membrane may serve as an auxiliary signal of the fed state that promotes lipid synthesis in response to nutrient availability.
[Mh] Termos MeSH primário: Retículo Endoplasmático/metabolismo
Resistência à Insulina
Lipogênese
Obesidade/metabolismo
Fosfolipídeos/metabolismo
[Mh] Termos MeSH secundário: 1-Acilglicerofosfocolina O-Aciltransferase/genética
1-Acilglicerofosfocolina O-Aciltransferase/metabolismo
Animais
Retículo Endoplasmático/genética
Retículo Endoplasmático/patologia
Peptídeos e Proteínas de Sinalização Intracelular/genética
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
Receptores X do Fígado/genética
Receptores X do Fígado/metabolismo
Proteínas de Membrana/genética
Proteínas de Membrana/metabolismo
Camundongos
Camundongos Transgênicos
Obesidade/genética
Obesidade/patologia
Fosfolipídeos/genética
Proteína de Ligação a Elemento Regulador de Esterol 1/genética
Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Intracellular Signaling Peptides and Proteins); 0 (Liver X Receptors); 0 (Membrane Proteins); 0 (Phospholipids); 0 (SREBP cleavage-activating protein); 0 (Srebf1 protein, mouse); 0 (Sterol Regulatory Element Binding Protein 1); EC 2.3.1.23 (1-Acylglycerophosphocholine O-Acyltransferase); EC 2.3.1.23 (LPCAT3 protein, mouse)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170829
[St] Status:MEDLINE


  8 / 2309 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28822685
[Au] Autor:Athithan V; Srikumar K
[Ad] Endereço:Dept. of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Pondicherry 605014, India.
[Ti] Título:28-Homocastasterone down regulates blood glucose, cholesterol, triglycerides, SREBP1c and activates LxR expression in normal & diabetic male rat.
[So] Source:Chem Biol Interact;277:8-20, 2017 Nov 01.
[Is] ISSN:1872-7786
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Plant steroids are being recognized as influential secondary bio factors, assimilating in animal tissues through diet and affecting their cellular metabolic function to varying degree. They modulate catalytic and signaling functions in mammalian cells, affecting cellular homeostasis. The effect of phyto brassinosteroid ketoisoform 28-homocastasterone (28-HC), was assessed for its influence on blood glucose, plasma lipid and selective signal marker levels in normal and diabetic male wistar rat models. A 15 day oral feed regimen employing the experimental rat, noted that circulating blood glucose, cholesterol and triglyceride level in diabetic rat were markedly reduced by this compound. This study confirmed that the keto form had anti-hyperglycemic and anti-lipidemic potency associated with it and was available to man and animals in their diet. Western blots of marker protein, PCR amplicons of marker mRNA expressions and In Silico studies suggested that 28-HCeffect is being mediated through LxR molecular operatives in the rat cell.
[Mh] Termos MeSH primário: Glicemia/análise
Colestanonas/uso terapêutico
Colesterol/sangue
Diabetes Mellitus Experimental/tratamento farmacológico
Hipoglicemiantes/uso terapêutico
Receptores X do Fígado/análise
Proteína de Ligação a Elemento Regulador de Esterol 1/sangue
Triglicerídeos/sangue
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Diabetes Mellitus Experimental/sangue
Diabetes Mellitus Experimental/genética
Diabetes Mellitus Experimental/patologia
Fígado/efeitos dos fármacos
Fígado/metabolismo
Fígado/patologia
Receptores X do Fígado/genética
Masculino
Simulação de Acoplamento Molecular
Ratos
Ratos Wistar
Regulação para Cima/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Blood Glucose); 0 (Cholestanones); 0 (Hypoglycemic Agents); 0 (Liver X Receptors); 0 (Sterol Regulatory Element Binding Protein 1); 0 (Triglycerides); 83509-42-6 (homocastasterone); 97C5T2UQ7J (Cholesterol)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171108
[Lr] Data última revisão:
171108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170821
[St] Status:MEDLINE


  9 / 2309 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28807695
[Au] Autor:Monzel JV; Budde T; Meyer Zu Schwabedissen HE; Schwebe M; Bien-Möller S; Lütjohann D; Kroemer HK; Jedlitschky G; Grube M
[Ad] Endereço:Dept. of Pharmacology at the Center of Drug Absorption and Transport (C_DAT), University Medicine, Greifswald, Germany.
[Ti] Título:Doxorubicin enhances oxysterol levels resulting in a LXR-mediated upregulation of cardiac cholesterol transporters.
[So] Source:Biochem Pharmacol;144:108-119, 2017 Nov 15.
[Is] ISSN:1873-2968
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The anthracycline-mediated cardiotoxicity is still not completely understood. To examine the impact of cholesterol metabolism and transport in this context, cholesterol and oxysterol levels as well as the expression of the cholesterol transporters ABCA1 and ABCG1 were analyzed in doxorubicin-treated HL-1 murine cardiomyocytes as well as in mouse model for acute doxorubicin-induced cardiotoxicity. Doxorubicin-treated HL-1 cells exhibited enhanced cholesterol (153±20% of control), oxysterol (24S-hydroxycholesterol: 206±29% of control) and cholesterol precursor levels (lathosterol: 122±12% of control; desmosterol: 188±10% of control) indicating enhanced cholesterol synthesis. Moreover, abca1 and abcg1 were upregulated on mRNA, protein and functional level caused by a doxorubicin-mediated activation of the nuclear receptor LXR. In addition, the oxysterols not only induced the abca1 and abcg1 in HL-1 cells but also enhanced the expression of endothelin-1 and transforming growth factor-ß, which have already been identified as important factors in doxorubicin-induced cardiotoxicity. These in vitro findings were verified in a murine model for acute doxorubicin-induced cardiotoxicity, demonstrating elevated cardiac (2.1±0.2vs. 3.6±1.0ng/mg) and systemic cholesterol levels (105.0±8.4vs. 130.0±4.3mg/dl), respectively, as well as enhanced oxysterol levels such as cardiac 24S-hydroxycholesterol (2.1±0.2vs. 3.6±1.0ng/mg). In line with these findings cardiac mRNA expression of abca1 (303% of control) and abcg1 (161% of control) was induced. Taken together, our data demonstrate enhanced cholesterol and oxysterol levels by doxorubicin, resulting in a LXR-dependent upregulation of abca1 and abcg1. In this context, the cytotoxic effects of oxysterols and their impact on cardiac gene expression should be considered as an important factor in doxorubicin-induced cardiotoxicity.
[Mh] Termos MeSH primário: Transportador 1 de Cassete de Ligação de ATP/biossíntese
Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/biossíntese
Doxorrubicina/farmacologia
Receptores X do Fígado/fisiologia
Miócitos Cardíacos/metabolismo
Oxisteróis/metabolismo
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Colesterol/metabolismo
Relação Dose-Resposta a Droga
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Miócitos Cardíacos/efeitos dos fármacos
Regulação para Cima/efeitos dos fármacos
Regulação para Cima/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ABCA1 protein, mouse); 0 (ABCG1 protein, mouse); 0 (ATP Binding Cassette Transporter 1); 0 (ATP Binding Cassette Transporter, Sub-Family G, Member 1); 0 (Liver X Receptors); 0 (Oxysterols); 80168379AG (Doxorubicin); 97C5T2UQ7J (Cholesterol)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170816
[St] Status:MEDLINE


  10 / 2309 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28794002
[Au] Autor:Li Z; Martin M; Zhang J; Huang HY; Bai L; Zhang J; Kang J; He M; Li J; Maurya MR; Gupta S; Zhou G; Sangwung P; Xu YJ; Lei T; Huang HD; Jain M; Jain MK; Subramaniam S; Shyy JY
[Ad] Endereço:From Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, China (Z.L., Jin Zhang, L.B., Jiao Zhang, M.H., J.L., T.L., J.Y.-J.S.); Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Educatio
[Ti] Título:Krüppel-Like Factor 4 Regulation of Cholesterol-25-Hydroxylase and Liver X Receptor Mitigates Atherosclerosis Susceptibility.
[So] Source:Circulation;136(14):1315-1330, 2017 Oct 03.
[Is] ISSN:1524-4539
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Atherosclerosis is a multifaceted inflammatory disease involving cells in the vascular wall (eg, endothelial cells [ECs]), as well as circulating and resident immunogenic cells (eg, monocytes/macrophages). Acting as a ligand for liver X receptor (LXR), but an inhibitor of SREBP2 (sterol regulatory element-binding protein 2), 25-hydroxycholesterol, and its catalyzing enzyme cholesterol-25-hydroxylase (Ch25h) are important in regulating cellular inflammatory status and cholesterol biosynthesis in both ECs and monocytes/macrophages. METHODS: Bioinformatic analyses were used to investigate RNA-sequencing data to identify cholesterol oxidation and efflux genes regulated by Krüppel-like factor 4 (KLF4). In vitro experiments involving cultured ECs and macrophages and in vivo methods involving mice with Ch25h ablation were then used to explore the atheroprotective role of KLF4-Ch25h/LXR. RESULTS: Vasoprotective stimuli increased the expression of Ch25h and LXR via KLF4. The KLF4-Ch25h/LXR homeostatic axis functions through suppressing inflammation, evidenced by the reduction of inflammasome activity in ECs and the promotion of M1 to M2 phenotypic transition in macrophages. The increased atherosclerosis in apolipoprotein E /Ch25h mice further demonstrates the beneficial role of the KLF4-Ch25h/LXR axis in vascular function and disease. CONCLUSIONS: KLF4 transactivates Ch25h and LXR, thereby promoting the synergistic effects between ECs and macrophages to protect against atherosclerosis susceptibility.
[Mh] Termos MeSH primário: Aterosclerose/etiologia
Expressão Gênica/genética
Fatores de Transcrição Kruppel-Like/metabolismo
Receptores X do Fígado/metabolismo
[Mh] Termos MeSH secundário: Animais
Seres Humanos
Hidroxicolesteróis
Receptores X do Fígado/análise
Masculino
Camundongos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (GKLF protein); 0 (Hydroxycholesterols); 0 (Kruppel-Like Transcription Factors); 0 (Liver X Receptors); 767JTD2N31 (25-hydroxycholesterol)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171004
[Lr] Data última revisão:
171004
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170811
[St] Status:MEDLINE
[do] DOI:10.1161/CIRCULATIONAHA.117.027462



página 1 de 231 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