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Pesquisa : D08.811.913.050.134.415.500.575.249 [Categoria DeCS]
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[PMID]:28460484
[Au] Autor:Wiese M; Walther N; Diederichs C; Schill F; Monecke S; Salinas G; Sturm D; Pfister SM; Dressel R; Johnsen SA; Kramm CM
[Ad] Endereço:Division of Pediatric Hematology and Oncology, Department of Child and Adolescent Health, University Medical Center Goettingen, Goettingen, Germany.
[Ti] Título:The ß-catenin/CBP-antagonist ICG-001 inhibits pediatric glioma tumorigenicity in a Wnt-independent manner.
[So] Source:Oncotarget;8(16):27300-27313, 2017 Apr 18.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Pediatric high-grade gliomas (pedHGG) belong to the most aggressive cancers in children with a poor prognosis due to a lack of efficient therapeutic strategies. The ß-catenin/Wnt-signaling pathway was shown to hold promising potential as a treatment target in adult high-grade gliomas by abrogating tumor cell invasion and the acquisition of stem cell-like characteristics. Since pedHGG differ from their adult counterparts in genetically and biologically we aimed to investigate the effects of ß-catenin/Wnt-signaling pathway-inhibition by the ß-catenin/CBP antagonist ICG-001 in pedHGG cell lines. In contrast to adult HGG, pedHGG cells displayed minimal detectable canonical Wnt-signaling activity. Nevertheless, low doses of ICG-001 inhibited cell migration/invasion, tumorsphere- and colony formation, proliferation in vitro as well as tumor growth in vivo/ovo, suggesting that ICG-001 affects pedHGG tumor cell characteristics independent of ß-catenin/Wnt-signaling. RNA-sequencing analyses support a Wnt/ß-catenin-independent effect of ICG-001 on target gene transcription, revealing strong effects on genes involved in cellular metabolic/biosynthetic processes and cell cycle progression. Among these, high mRNA expression of cell cycle regulator JDP2 was found to confer a better prognosis for pedHGG patients. In conclusion, ICG-001 might offer an effective treatment option for pedHGG patients functioning to regulate cell phenotype and gene expression programs in absence of Wnt/ß-catenin signaling-activity.
[Mh] Termos MeSH primário: Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia
Proteína de Ligação a CREB/antagonistas & inibidores
Transformação Celular Neoplásica/efeitos dos fármacos
Transformação Celular Neoplásica/metabolismo
Glioma/metabolismo
Pirimidinonas/farmacologia
Via de Sinalização Wnt/efeitos dos fármacos
beta Catenina/antagonistas & inibidores
[Mh] Termos MeSH secundário: Adolescente
Animais
Linhagem Celular Tumoral
Movimento Celular/efeitos dos fármacos
Movimento Celular/genética
Autorrenovação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Transformação Celular Neoplásica/genética
Embrião de Galinha
Criança
Pré-Escolar
Bases de Dados Genéticas
Modelos Animais de Doenças
Glioma/genética
Glioma/mortalidade
Glioma/patologia
Seres Humanos
Estimativa de Kaplan-Meier
Células-Tronco Neoplásicas/citologia
Células-Tronco Neoplásicas/efeitos dos fármacos
Células-Tronco Neoplásicas/metabolismo
Prognóstico
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bridged Bicyclo Compounds, Heterocyclic); 0 (ICG 001); 0 (Pyrimidinones); 0 (beta Catenin); EC 2.3.1.48 (CREB-Binding Protein); EC 2.3.1.48 (CREBBP protein, human)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.15934


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[PMID]:29217191
[Au] Autor:Yoshida K; Nakai A; Kaneshiro K; Hashimoto N; Suzuki K; Uchida K; Hashimoto T; Kawasaki Y; Tateishi K; Nakagawa N; Shibanuma N; Sakai Y; Hashiramoto A
[Ad] Endereço:Department of Biophysics, Kobe University Graduate School of Health Sciences, Kobe 654-0142, Japan.
[Ti] Título:TNF-α induces expression of the circadian clock gene Bmal1 via dual calcium-dependent pathways in rheumatoid synovial cells.
[So] Source:Biochem Biophys Res Commun;495(2):1675-1680, 2018 01 08.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Tumor necrosis factor (TNF)-α is responsible for expressions of several clock genes and affects joint symptoms of rheumatoid arthritis (RA) with diurnal fluctuation. We tried to determine the mechanism involved in over-expression of Bmal1, induced by TNF-α, in primary cultured rheumatoid synovial cells. Cells were incubated with intra-cellular Ca chelator BAPTA-AM, calcineurin inhibitor FK506 and p300/CBP (CREB binding protein) inhibitor C646, respectively, or transfected with p300 and CBP small interfering RNA (siRNA) before stimulation with TNF-α. Oscillation phase and amplitude of Bmal1, transcriptional activator Rorα, transcriptional repressor Rev-erbα, and histone acetyltransferases (p300 and Cbp) were evaluated by quantitative real-time PCR. As results, TNF-α did not influence the oscillation phase of Rev-erbα, while enhanced those of Rorα, resulting in over-expression of Bmal1. When Ca influx was inhibited by BAPTA-AM, TNF-α-mediated up-regulation of Rorα was cancelled, however, that of Bmal1 was still apparent. When we further explored another pathway between TNF-α and Bmal1, TNF-α suppressed the expression of Rev-erbα in the absence of Ca influx, as well as those of p300 and Cbp genes. Finally, actions of TNF-α, in increasing Bmal1/Rorα and decreasing Rev-erbα, were cancelled by C646 treatment or silencing of both p300 and Cbp. In conclusion, we determined a novel role of TNF-α in inducing Bmal1 via dual calcium dependent pathways; Rorα was up-regulated in the presence of Ca influx and Rev-erbα was down-regulated in the absence of that. Results proposed that inhibition of p300/CBP could be new therapeutic targets for RA.
[Mh] Termos MeSH primário: Fatores de Transcrição ARNTL/genética
Artrite Reumatoide/genética
Artrite Reumatoide/metabolismo
Sinalização do Cálcio
Relógios Circadianos/genética
Membrana Sinovial/metabolismo
Fator de Necrose Tumoral alfa/metabolismo
[Mh] Termos MeSH secundário: Artrite Reumatoide/patologia
Benzoatos/farmacologia
Proteína de Ligação a CREB/antagonistas & inibidores
Proteína de Ligação a CREB/genética
Quelantes de Cálcio/farmacologia
Sinalização do Cálcio/efeitos dos fármacos
Células Cultivadas
Proteína p300 Associada a E1A/antagonistas & inibidores
Proteína p300 Associada a E1A/genética
Ácido Egtázico/análogos & derivados
Ácido Egtázico/farmacologia
Expressão Gênica/efeitos dos fármacos
Seres Humanos
Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/genética
Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/genética
Pirazóis/farmacologia
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
RNA Interferente Pequeno/genética
Membrana Sinovial/efeitos dos fármacos
Membrana Sinovial/patologia
Fator de Necrose Tumoral alfa/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (ARNTL Transcription Factors); 0 (ARNTL protein, human); 0 (Benzoates); 0 (C646 compound); 0 (Calcium Chelating Agents); 0 (NR1D1 protein, human); 0 (Nuclear Receptor Subfamily 1, Group D, Member 1); 0 (Nuclear Receptor Subfamily 1, Group F, Member 1); 0 (Pyrazoles); 0 (RNA, Messenger); 0 (RNA, Small Interfering); 0 (RORA protein, human); 0 (Tumor Necrosis Factor-alpha); 139890-68-9 (1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester); 526U7A2651 (Egtazic Acid); EC 2.3.1.48 (CREB-Binding Protein); EC 2.3.1.48 (CREBBP protein, human); EC 2.3.1.48 (E1A-Associated p300 Protein); EC 2.3.1.48 (EP300 protein, human)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171209
[St] Status:MEDLINE


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[PMID]:29287093
[Au] Autor:Hossain ME; Matsuzaki K; Katakura M; Sugimoto N; Mamun AA; Islam R; Hashimoto M; Shido O
[Ad] Endereço:Department of Environmental Physiology, Faculty of Medicine, Shimane University, Enya-cho, Izumo, Japan.
[Ti] Título:Direct exposure to mild heat promotes proliferation and neuronal differentiation of neural stem/progenitor cells in vitro.
[So] Source:PLoS One;12(12):e0190356, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Heat acclimation in rats is associated with enhanced neurogenesis in thermoregulatory centers of the hypothalamus. To elucidate the mechanisms for heat acclimation, we investigated the effects of direct mild heat exposure on the proliferation and differentiation of neural stem/progenitor cells (NSCs/NPCs). The NSCs/NPCs isolated from forebrain cortices of 14.5-day-old rat fetuses were propagated as neurospheres at either 37.0°C (control) or 38.5°C (mild heat exposure) for four days, and the effects on proliferation were investigated by MTS cell viability assay, measurement of neurosphere diameter, and counting the total number of cells. The mRNA expressions of heat shock proteins (HSPs) and brain-derived neurotrophic factor (BDNF), cAMP response element-binding (CREB) protein and Akt phosphorylation levels, and intracellular reactive oxygen species (ROS) levels were analyzed using real time PCR, Western blotting and CM-H2DCFDA assay respectively. Heat exposure under proliferation condition increased NSC/NPC viability, neurosphere diameter, and cell count. BDNF mRNA expression, CREB phosphorylation, and ROS level were also increased by heat exposure. Heat exposure increased HSP27 mRNA expression concomitant with enhanced p-Akt level. Moreover, treatment with LY294002 (a PI3K inhibitor) abolished the effects of heat exposure on NSC/NPC proliferation. Furthermore, heat exposure under differentiation conditions increased the proportion of cells positive for Tuj1 (a neuronal marker). These findings suggest that mild heat exposure increases NSC/NPC proliferation, possibly through activation of the Akt pathway, and also enhances neuronal differentiation. Direct effects of temperature on NSCs/NPCs may be one of the mechanisms involved in hypothalamic neurogenesis in heat-acclimated rats. Such heat-induced neurogenesis could also be an effective therapeutic strategy for neurodegenerative diseases.
[Mh] Termos MeSH primário: Diferenciação Celular
Proliferação Celular
Temperatura Alta
Células-Tronco Neurais/citologia
Neurônios/citologia
[Mh] Termos MeSH secundário: Animais
Fator Neurotrófico Derivado do Encéfalo/metabolismo
Proteína de Ligação a CREB/metabolismo
Proliferação Celular/efeitos dos fármacos
Células Cultivadas
Cromonas/farmacologia
Proteínas de Choque Térmico/metabolismo
Morfolinas/farmacologia
Células-Tronco Neurais/metabolismo
Neurônios/metabolismo
Fosforilação
Proteínas Proto-Oncogênicas c-akt/metabolismo
Ratos
Espécies Reativas de Oxigênio/metabolismo
Reação em Cadeia da Polimerase em Tempo Real
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Brain-Derived Neurotrophic Factor); 0 (Chromones); 0 (Heat-Shock Proteins); 0 (Morpholines); 0 (Reactive Oxygen Species); 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one); EC 2.3.1.48 (CREB-Binding Protein); EC 2.3.1.48 (Crebbp protein, rat); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180207
[Lr] Data última revisão:
180207
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171230
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190356


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[PMID]:28452938
[Au] Autor:Casarini L; Riccetti L; De Pascali F; Gilioli L; Marino M; Vecchi E; Morini D; Nicoli A; La Sala GB; Simoni M
[Ad] Endereço:Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, NOCSAE, via P. Giardini 1355, 41126 Modena, Italy. livio.casarini@unimore.it.
[Ti] Título:Estrogen Modulates Specific Life and Death Signals Induced by LH and hCG in Human Primary Granulosa Cells In Vitro.
[So] Source:Int J Mol Sci;18(5), 2017 Apr 28.
[Is] ISSN:1422-0067
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) are glycoprotein hormones used for assisted reproduction acting on the same receptor (LHCGR) and mediating different intracellular signaling. We evaluated the pro- and anti-apoptotic effect of 100 pM LH or hCG, in the presence or in the absence of 200 pg/mL 17ß-estradiol, in long-term, serum-starved human primary granulosa cells (hGLC) and a transfected granulosa cell line overexpressing LHCGR (hGL5/LHCGR). To this purpose, phospho-extracellular-regulated kinase 1/2 (pERK1/2), protein kinase B (pAKT), cAMP-responsive element binding protein (pCREB) activation and procaspase 3 cleavage were evaluated over three days by Western blotting, along with the expression of target genes by real-time PCR and cell viability by colorimetric assay. We found that LH induced predominant pERK1/2 and pAKT activation , and anti-apoptotic gene expression, while hCG mediated more potent CREB phosphorylation, expression of and procaspase 3 cleavage than LH. Cell treatment by LH is accompanied by increased (serum-starved) cell viability, while hCG decreased the number of viable cells. The hCG-specific, pro-apoptotic effect was blocked by a physiological dose of 17ß-estradiol, resulting in pAKT activation, lack of procaspase 3 cleavage and increased cell viability. These results confirm that relatively high levels of steroidogenic pathway activation are linked to pro-apoptotic signals in vitro, which may be counteracted by other factors, i.e., estrogens.
[Mh] Termos MeSH primário: Gonadotropina Coriônica/farmacologia
Estradiol/farmacologia
Hormônio Luteinizante/farmacologia
Transdução de Sinais/efeitos dos fármacos
[Mh] Termos MeSH secundário: Aromatase/metabolismo
Proteína de Ligação a CREB/metabolismo
Caspase 3/genética
Caspase 3/metabolismo
Sobrevivência Celular/efeitos dos fármacos
Células Cultivadas
Feminino
Expressão Gênica/efeitos dos fármacos
Células da Granulosa/citologia
Células da Granulosa/efeitos dos fármacos
Células da Granulosa/metabolismo
Seres Humanos
Proteína Quinase 1 Ativada por Mitógeno/metabolismo
Proteína Quinase 3 Ativada por Mitógeno/metabolismo
Fosforilação/efeitos dos fármacos
Proteínas Proto-Oncogênicas c-akt/metabolismo
Proteína Supressora de Tumor p53/genética
Proteína Supressora de Tumor p53/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Chorionic Gonadotropin); 0 (Tumor Suppressor Protein p53); 4TI98Z838E (Estradiol); 9002-67-9 (Luteinizing Hormone); EC 1.14.14.1 (Aromatase); EC 1.14.14.1 (CYP19A1 protein, human); EC 2.3.1.48 (CREB-Binding Protein); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3); EC 3.4.22.- (Caspase 3)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180122
[Lr] Data última revisão:
180122
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE


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[PMID]:28963930
[Au] Autor:Li Y; Yu Q; Zhao W; Zhang J; Liu W; Huang M; Zeng X
[Ad] Endereço:Department of Respiratory & Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, China.
[Ti] Título:Oligomeric proanthocyanidins attenuate airway inflammation in asthma by inhibiting dendritic cells maturation.
[So] Source:Mol Immunol;91:209-217, 2017 11.
[Is] ISSN:1872-9142
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:To date, although a promising anti-inflammatory activity of oligomeric proanthocyanidins (OPCs) has been observed in asthma, the mechanism responsible for these immunomodulatory properties remains obscure. Dendritic cells (DCs) that reside in the airway have been widely perceived as an important contributor to asthma. Our study was to demonstrate OPCs' effects on maturation and immunoregulation of pulmonary CD11c dendritic cells (DCs). BALB/c mice were exposed to ovalbumin (OVA) to induce murine model of asthma. In addition, pulmonary DCs and bone marrow-derived DCs (BMDCs) cultures were used to evaluate impacts of OPCs on DCs function. The results obtained here indicated that OPCs treatment dramatically reduced airway inflammation, such as the infiltration of inflammatory cells and the levels of allergen-specific serum IgE and Th2 cytokines. The expression of co-stimulatory molecules especially CD86 distributed on pulmonary DCs and bone marrow-derived DCs (BMDCs) also markedly declined. The phosphorylation of cAMP responsive element-binding protein (CREB) was significantly inhibited while no changes were observed in the expression of cAMP responsive element modulator (CREM). By transferring BMDCs into the airways of naïve mice, we found that OPCs-treated DCs (DC+OVA+OPC) were much less potent in promoting CD4 T cells proliferation than OVA-pulsed DCs (DC+OVA), followed by the ameliorated eosinophilic inflammation in airway. Our findings tailor a novel profile of OPCs in the regulation of DCs function, shedding new light on the therapeutic potential of OPCs in asthma management.
[Mh] Termos MeSH primário: Asma/imunologia
Células Dendríticas/imunologia
Pulmão/imunologia
Proantocianidinas/farmacologia
[Mh] Termos MeSH secundário: Animais
Asma/induzido quimicamente
Asma/patologia
Antígeno B7-2/imunologia
Antígeno CD11c/imunologia
Proteína de Ligação a CREB/imunologia
Proliferação Celular/efeitos dos fármacos
Citocinas/imunologia
Células Dendríticas/patologia
Feminino
Imunoglobulina E/imunologia
Inflamação/induzido quimicamente
Inflamação/imunologia
Inflamação/patologia
Pulmão/patologia
Camundongos
Camundongos Endogâmicos BALB C
Fosforilação/efeitos dos fármacos
Fosforilação/imunologia
Células Th2/imunologia
Células Th2/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (B7-2 Antigen); 0 (CD11c Antigen); 0 (Cd86 protein, mouse); 0 (Cytokines); 0 (Proanthocyanidins); 37341-29-0 (Immunoglobulin E); EC 2.3.1.48 (CREB-Binding Protein); EC 2.3.1.48 (Crebbp protein, mouse)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171120
[Lr] Data última revisão:
171120
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171001
[St] Status:MEDLINE


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[PMID]:28887131
[Au] Autor:Misawa H; Ohashi W; Tomita K; Hattori K; Shimada Y; Hattori Y
[Ad] Endereço:Department of Molecular and Medical Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan; Department of Japanese Oriental Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
[Ti] Título:Prostacyclin mimetics afford protection against lipopolysaccharide/d-galactosamine-induced acute liver injury in mice.
[So] Source:Toxicol Appl Pharmacol;334:55-65, 2017 Nov 01.
[Is] ISSN:1096-0333
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Prostacyclin (PGI ) serves as a protective, anti-inflammatory mediator and PGI mimetics may be useful as a hepatoprotective agent. We examined whether two PGI mimetics, ONO-1301 and beraprost, are beneficial in acute liver injury and attempted to delineate the possible mechanism underlying the hepatoprotective effect. Acute liver injury was induced by lipopolysaccharide/d-galactosamine (LPS/GalN) in mice. Mice were given an intraperitoneal injection of PGI mimetics 1h before LPS/GalN challenge. Both ONO-1301 and beraprost significantly declined the LPS/GalN-induced increase in serum aminotransferase activity. ONO-1301 and, to a lesser extent, beraprost inhibited hepatic gene expression levels of pro-inflammatory cytokines, which were sharply elevated by LPS/GalN. The hepatoprotective effects of ONO-1301, to a lesser extent, of beraprost were also supported by liver histopathological examinations. The PGI receptor antagonist CAY10441 abrogated their hepatoprotective effects. The mechanisms behind the benefit of PGI mimetics in reducing LPS/GalN-induced liver injury involved, in part, their suppressive effects on increased generation of reactive oxygen species (ROS), since their ability to prevent LPS/GalN-induced hepatic apoptosis was mimicked by the antioxidant N-acetyl-l-cysteine. They significantly diminished LPS/GalN-induced activation of signal transducers and activators of transcription 3 (STAT3) in liver tissues, an effect which was highly associated with their hepatoprotective effects. We indicate that IP receptor activation with PGI mimetics can rescue the damage in the liver induced by LPS/GalN by undermining activation of STAT3 and leading to a lower production of ROS. Our findings point to PGI mimetics, especially ONO-1301, as a potential novel therapeutic modality for the treatment of acute liver injury.
[Mh] Termos MeSH primário: Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle
Epoprostenol/análogos & derivados
Galactosamina/toxicidade
Lipopolissacarídeos/toxicidade
Piridinas/farmacologia
[Mh] Termos MeSH secundário: Animais
Compostos de Benzil/farmacologia
Proteína de Ligação a CREB/genética
Proteína de Ligação a CREB/metabolismo
Epoprostenol/farmacologia
Galactosamina/administração & dosagem
Regulação da Expressão Gênica
Imidazóis/farmacologia
Lipopolissacarídeos/administração & dosagem
Camundongos
Quinases de Proteína Quinase Ativadas por Mitógeno/genética
Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo
Prostaglandinas I/química
Prostaglandinas I/farmacologia
Espécies Reativas de Oxigênio
Fator de Transcrição STAT3/genética
Fator de Transcrição STAT3/metabolismo
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 ((2-(4-(4-isopropoxybenzyl)-phenylamino) imidazoline)); 0 (Benzyl Compounds); 0 (Imidazoles); 0 (Lipopolysaccharides); 0 (Prostaglandins I); 0 (Pyridines); 0 (Reactive Oxygen Species); 0 (STAT3 Transcription Factor); 0 (Stat3 protein, mouse); 176391-41-6 (ONO 1301); 35E3NJJ4O6 (beraprost); 7535-00-4 (Galactosamine); DCR9Z582X0 (Epoprostenol); EC 2.3.1.48 (CREB-Binding Protein); EC 2.3.1.48 (Crebbp protein, mouse); EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170910
[St] Status:MEDLINE


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[PMID]:28881028
[Au] Autor:Guirao V; Martí-Sistac O; DeGregorio-Rocasolano N; Ponce J; Dávalos A; Gasull T
[Ad] Endereço:Cellular and Molecular Neurobiology Research Group, Department of Neurosciences, Germans Trias i Pujol Research Institute, Badalona, Catalonia, Spain.
[Ti] Título:Specific rescue by ortho-hydroxy atorvastatin of cortical GABAergic neurons from previous oxygen/glucose deprivation: role of pCREB.
[So] Source:J Neurochem;143(3):359-374, 2017 Nov.
[Is] ISSN:1471-4159
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The statin atorvastatin (ATV) given as a post-treatment has been reported beneficial in stroke, although the mechanisms involved are not well understood so far. Here, we investigated in vitro the effect of post-treatment with ATV and its main bioactive metabolite ortho-hydroxy ATV (o-ATV) on neuroprotection after oxygen and glucose deprivation (OGD), and the role of the pro-survival cAMP response element-binding protein (CREB). Post-OGD treatment of primary cultures of rat cortical neurons with o-ATV, but not ATV, provided neuroprotection to a specific subset of cortical neurons that were large and positive for glutamic acid decarboxylase (large-GAD neurons, GABAergic). Significantly, only these GABAergic neurons showed an increase in phosphorylated CREB (pCREB) early after neuronal cultures were treated post-OGD with o-ATV. We found that o-ATV, but not ATV, increased the neuronal uptake of glutamate from the medium; this provides a rationale for the specific effect of o-ATV on pCREB in large-GABAergic neurons, which have a higher ratio of synaptic (pCREB-promoting) vs extrasynaptic (pCREB-reducing) N-methyl-D-aspartate (NMDA) receptors (NMDAR) than that of small-non-GABAergic neurons. When we pharmacologically increased pCREB levels post-OGD in non-GABAergic neurons, through the selective activation of synaptic NMDAR, we observed as well long-lasting neuronal survival. We propose that the statin metabolite o-ATV given post-OGD boosts the intrinsic pro-survival factor pCREB in large-GABAergic cortical neurons in vitro, this contributing to protect them from OGD.
[Mh] Termos MeSH primário: Atorvastatina Cálcica/análogos & derivados
Hipóxia Celular/efeitos dos fármacos
Córtex Cerebral/citologia
Neurônios GABAérgicos/efeitos dos fármacos
Glucose/deficiência
Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia
[Mh] Termos MeSH secundário: Animais
Atorvastatina Cálcica/farmacologia
Proteína de Ligação a CREB/metabolismo
Morte Celular/efeitos dos fármacos
Células Cultivadas
Embrião de Mamíferos
Feminino
Ácido Glutâmico/farmacocinética
Masculino
Proteínas do Tecido Nervoso/metabolismo
Ratos
Ratos Sprague-Dawley
Receptores de N-Metil-D-Aspartato/metabolismo
Trítio/farmacocinética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (2-hydroxyatorvastatin); 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors); 0 (Nerve Tissue Proteins); 0 (Receptors, N-Methyl-D-Aspartate); 10028-17-8 (Tritium); 3KX376GY7L (Glutamic Acid); 48A5M73Z4Q (Atorvastatin Calcium); EC 2.3.1.48 (CREB-Binding Protein); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171102
[Lr] Data última revisão:
171102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170908
[St] Status:MEDLINE
[do] DOI:10.1111/jnc.14210


  8 / 2226 MEDLINE  
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[PMID]:28825697
[Au] Autor:Horton SJ; Giotopoulos G; Yun H; Vohra S; Sheppard O; Bashford-Rogers R; Rashid M; Clipson A; Chan WI; Sasca D; Yiangou L; Osaki H; Basheer F; Gallipoli P; Burrows N; Erdem A; Sybirna A; Foerster S; Zhao W; Sustic T; Petrunkina Harrison A; Laurenti E; Okosun J; Hodson D; Wright P; Smith KG; Maxwell P; Fitzgibbon J; Du MQ; Adams DJ; Huntly BJP
[Ad] Endereço:Wellcome Trust-MRC Cambridge Stem Cell Institute, Cambridge, UK.
[Ti] Título:Early loss of Crebbp confers malignant stem cell properties on lymphoid progenitors.
[So] Source:Nat Cell Biol;19(9):1093-1104, 2017 Sep.
[Is] ISSN:1476-4679
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Loss-of-function mutations of cyclic-AMP response element binding protein, binding protein (CREBBP) are prevalent in lymphoid malignancies. However, the tumour suppressor functions of CREBBP remain unclear. We demonstrate that loss of Crebbp in murine haematopoietic stem and progenitor cells (HSPCs) leads to increased development of B-cell lymphomas. This is preceded by accumulation of hyperproliferative lymphoid progenitors with a defective DNA damage response (DDR) due to a failure to acetylate p53. We identify a premalignant lymphoma stem cell population with decreased H3K27ac, which undergoes transcriptional and genetic evolution due to the altered DDR, resulting in lymphomagenesis. Importantly, when Crebbp is lost later in lymphopoiesis, cellular abnormalities are lost and tumour generation is attenuated. We also document that CREBBP mutations may occur in HSPCs from patients with CREBBP-mutated lymphoma. These data suggest that earlier loss of Crebbp is advantageous for lymphoid transformation and inform the cellular origins and subsequent evolution of lymphoid malignancies.
[Mh] Termos MeSH primário: Proteína de Ligação a CREB/deficiência
Proteína de Ligação a CREB/metabolismo
Transformação Celular Neoplásica/metabolismo
Células Progenitoras Linfoides/metabolismo
Linfoma/metabolismo
Células-Tronco Neoplásicas/metabolismo
[Mh] Termos MeSH secundário: Acetilação
Animais
Proteína de Ligação a CREB/genética
Proliferação Celular
Autorrenovação Celular
Transformação Celular Neoplásica/genética
Transformação Celular Neoplásica/patologia
Células Cultivadas
Dano ao DNA
Epigênese Genética
Regulação Neoplásica da Expressão Gênica
Predisposição Genética para Doença
Histonas/metabolismo
Linfangiogênese
Células Progenitoras Linfoides/patologia
Linfoma/genética
Linfoma/patologia
Linfopoese
Metilação
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Mutação
Células-Tronco Neoplásicas/patologia
Fenótipo
Transdução de Sinais
Fatores de Tempo
Transcrição Genética
Proteína Supressora de Tumor p53/genética
Proteína Supressora de Tumor p53/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Histones); 0 (Tumor Suppressor Protein p53); EC 2.3.1.48 (CREB-Binding Protein); EC 2.3.1.48 (CREBBP protein, human); EC 2.3.1.48 (Crebbp protein, mouse)
[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:170822
[St] Status:MEDLINE
[do] DOI:10.1038/ncb3597


  9 / 2226 MEDLINE  
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[PMID]:28815970
[Au] Autor:Xu L; Cheng A; Huang M; Zhang J; Jiang Y; Wang C; Li F; Bao H; Gao J; Wang N; Liu J; Wu J; Wong CCL; Ruan K
[Ad] Endereço:Hefei National Laboratory for Physical Science at the Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, China.
[Ti] Título:Structural insight into the recognition of acetylated histone H3K56ac mediated by the bromodomain of CREB-binding protein.
[So] Source:FEBS J;284(20):3422-3436, 2017 Oct.
[Is] ISSN:1742-4658
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The acetylation of lysine 56 of histone H3 (H3K56ac) enhances the binding affinity of histone chaperones to H3-H4 dimers. CREB-binding protein (CBP) possesses a bromodomain that recognizes H3K56 acetylation. CBP also possesses a histone acetyltransferase (HAT) domain, which has been shown to promote H3K56 acetylation of free histones to facilitate delivery of replication-dependent chaperones to acetylated histones for chromatin assembly. However, the mechanism by which the CBP bromodomain recognizes H3K56ac and the context in which such recognition occurs remain elusive. Here, we solved the crystal structure of the CBP bromodomain in complex with an H3K56ac peptide. Our data demonstrate that the CBP bromodomain recognizes H3K56ac with high affinity. Structural and affinity analyses reveal that the CBP bromodomain prefers an aromatic residue at the -2 position and an arginine at the -4 position from the acetyl-lysine, and that the CBP bromodomain selectively recognizes an extended conformation of the H3 αN helix that contains H3K56ac. We also demonstrate that the CBP bromodomain binds to H3K56ac in a recombinant H3-H4 dimer but not in a mono-nucleosome. Our results suggest that the CBP bromodomain selectively recognizes an extended conformation of the K56-acetylated H3 α region within an H3-H4 dimer, which is expected to facilitate the HAT activity of CBP for subsequent H3K56 acetylation of free histones. DATABASES: Coordinates of the CBP bromodomain in complex with H3K56ac as described in this article have been deposited in the PDB with accession number 5GH9.
[Mh] Termos MeSH primário: Proteína de Ligação a CREB/metabolismo
Histonas/química
Histonas/metabolismo
Processamento de Proteína Pós-Traducional
[Mh] Termos MeSH secundário: Acetilação
Sítios de Ligação
Proteína de Ligação a CREB/química
Cristalografia por Raios X
Histona Acetiltransferases/metabolismo
Seres Humanos
Lisina/química
Lisina/metabolismo
Nucleossomos/metabolismo
Fragmentos de Peptídeos/química
Fragmentos de Peptídeos/metabolismo
Ligação Proteica
Domínios Proteicos
Estrutura Terciária de Proteína
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Histones); 0 (Nucleosomes); 0 (Peptide Fragments); EC 2.3.1.48 (CREB-Binding Protein); EC 2.3.1.48 (Histone Acetyltransferases); K3Z4F929H6 (Lysine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171027
[Lr] Data última revisão:
171027
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170818
[St] Status:MEDLINE
[do] DOI:10.1111/febs.14198


  10 / 2226 MEDLINE  
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[PMID]:28701311
[Au] Autor:Gonzalez AA; Salinas-Parra N; Leach D; Navar LG; Prieto MC
[Ad] Endereço:Instituto de Química, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile; alexis.gonzalez@pucv.cl.
[Ti] Título:PGE upregulates renin through E-prostanoid receptor 1 via PKC/cAMP/CREB pathway in M-1 cells.
[So] Source:Am J Physiol Renal Physiol;313(4):F1038-F1049, 2017 Oct 01.
[Is] ISSN:1522-1466
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:During the early phase of ANG II-dependent hypertension, tubular PGE is increased. Renin synthesis and secretion in the collecting duct (CD) are upregulated by ANG II, contributing to further intratubular ANG II formation. However, what happens first and whether the triggering mechanism is independent of tubular ANG II remain unknown. PGE stimulates renin synthesis in juxtaglomerular cells via E-prostanoid (EP) receptors through the cAMP/cAMP-responsive element-binding (CREB) pathway. EP receptors are also expressed in the CD. Here, we tested the hypothesis that renin is upregulated by PGE in CD cells. The M-1 CD cell line expressed EP1, EP3, and EP4 but not EP2. Dose-response experiments, in the presence of ANG II type 1 receptor blockade with candesartan, demonstrated that 10 M PGE maximally increases renin mRNA (approximately 4-fold) and prorenin/renin protein levels (approximately 2-fold). This response was prevented by micromolar doses of SC-19220 (EP1 antagonist), attenuated by the EP4 antagonist, L-161982, and exacerbated by the highly selective EP3 antagonist, L-798106 (~10-fold increase). To evaluate further the signaling pathway involved, we used the PKC inhibitor calphostin C and transfections with PKCα dominant negative. Both strategies blunted the PGE -induced increases in cAMP levels, CREB phosphorylation, and augmentation of renin. Knockdown of the EP1 receptor and CREB also prevented renin upregulation. These results indicate that PGE increases CD renin expression through the EP1 receptor via the PKC/cAMP/CREB pathway. Therefore, we conclude that during the early stages of ANG II-dependent hypertension, there is augmentation of PGE that stimulates renin in the CD, resulting in increased tubular ANG II formation and further stimulation of renin.
[Mh] Termos MeSH primário: Proteína de Ligação a CREB/metabolismo
AMP Cíclico/metabolismo
Dinoprostona/farmacologia
Túbulos Renais Coletores/efeitos dos fármacos
Proteína Quinase C/metabolismo
Receptores de Prostaglandina E Subtipo EP1/agonistas
Sistema Renina-Angiotensina/efeitos dos fármacos
Renina/metabolismo
[Mh] Termos MeSH secundário: Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia
Animais
Proteína de Ligação a CREB/genética
Linhagem Celular
Proteínas Quinases Dependentes de AMP Cíclico/metabolismo
Relação Dose-Resposta a Droga
Túbulos Renais Coletores/enzimologia
Camundongos
Simulação de Acoplamento Molecular
Fosforilação
Antagonistas de Prostaglandina/farmacologia
Proteína Quinase C/antagonistas & inibidores
Proteína Quinase C/genética
Inibidores de Proteínas Quinases/farmacologia
Interferência de RNA
Receptores de Prostaglandina E Subtipo EP1/genética
Receptores de Prostaglandina E Subtipo EP1/metabolismo
Receptores de Prostaglandina E Subtipo EP3/metabolismo
Receptores de Prostaglandina E Subtipo EP4/metabolismo
Renina/genética
Transdução de Sinais/efeitos dos fármacos
Transfecção
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Angiotensin II Type 1 Receptor Blockers); 0 (Prostaglandin Antagonists); 0 (Protein Kinase Inhibitors); 0 (Ptger1 protein, mouse); 0 (Ptger3 protein, mouse); 0 (Ptger4 protein, mouse); 0 (Receptors, Prostaglandin E, EP1 Subtype); 0 (Receptors, Prostaglandin E, EP3 Subtype); 0 (Receptors, Prostaglandin E, EP4 Subtype); E0399OZS9N (Cyclic AMP); EC 2.3.1.48 (CREB-Binding Protein); EC 2.3.1.48 (Crebbp protein, mouse); EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases); EC 2.7.11.13 (Protein Kinase C); EC 3.4.23.15 (Renin); K7Q1JQR04M (Dinoprostone)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171108
[Lr] Data última revisão:
171108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170714
[St] Status:MEDLINE
[do] DOI:10.1152/ajprenal.00194.2017



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