Base de dados : MEDLINE
Pesquisa : D08.811.682.608.575.937 [Categoria DeCS]
Referências encontradas : 970 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 97 ir para página                         

  1 / 970 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29329317
[Au] Autor:Jeong BY; Lee HY; Park CG; Kang J; Yu SL; Choi DR; Han SY; Park MH; Cho S; Lee SY; Hwang WM; Yun SR; Ryu HM; Oh EJ; Park SH; Kim YL; Yoon SH
[Ad] Endereço:Department of Pharmacology, College of Medicine, Konyang University, Daejeon, Republic of Korea.
[Ti] Título:Oxidative stress caused by activation of NADPH oxidase 4 promotes contrast-induced acute kidney injury.
[So] Source:PLoS One;13(1):e0191034, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Contrast-induced acute kidney injury (CIAKI) is a leading cause of acute kidney injury following radiographic procedures. Intrarenal oxidative stress plays a critical role in CIAKI. Nicotinamide adenine dinucleotide 3-phosphate (NADPH) oxidases (Noxs) are important sources of reactive oxygen species (ROS). Among the various types of Noxs, Nox4 is expressed predominantly in the kidney in rodents. Here, we evaluated the role of Nox4 and benefit of Nox4 inhibition on CIAKI using in vivo and in vitro models. HK-2 cells were treated with iohexol, with or without Nox4 knockdown, or the most specific Nox1/4 inhibitor (GKT137831). Effects of Nox4 inhibition on CIAKI mice were examined. Expression of Nox4 in HK-2 cells was significantly increased following iohexol exposure. Silencing of Nox4 rescued the production of ROS, downregulated pro-inflammatory markers (particularly phospho-p38) implicated in CIAKI, and reduced Bax and caspase 3/7 activity, which resulted in increased cellular survival in iohexol-treated HK-2 cells. Pretreatment with GKT137831 replicated these effects by decreasing levels of phospho-p38. In a CIAKI mouse model, even though the improvement of plasma blood urea nitrogen was unclear, pretreatment with GKT137831 resulted in preserved structure, reduced expression of 8-hydroxy-2'-deoxyguanosine (8OHdG) and kidney injury molecule-1 (KIM-1), and reduced number of TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling)-positive cells. These results suggest Nox4 as a key source of reactive oxygen species responsible for CIAKI and provide a novel potential option for prevention of CIAKI.
[Mh] Termos MeSH primário: Lesão Renal Aguda/metabolismo
Meios de Contraste/efeitos adversos
NADPH Oxidase 4/metabolismo
Estresse Oxidativo
[Mh] Termos MeSH secundário: Lesão Renal Aguda/induzido quimicamente
Animais
Apoptose/efeitos dos fármacos
Linhagem Celular
Ativação Enzimática
Inativação Gênica
Seres Humanos
Iohexol/farmacologia
Túbulos Renais Proximais/citologia
Túbulos Renais Proximais/efeitos dos fármacos
Túbulos Renais Proximais/metabolismo
Masculino
Camundongos
Camundongos Endogâmicos C57BL
NADPH Oxidase 4/genética
Espécies Reativas de Oxigênio/metabolismo
Reação em Cadeia da Polimerase em Tempo Real
Superóxidos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Contrast Media); 0 (Reactive Oxygen Species); 11062-77-4 (Superoxides); 4419T9MX03 (Iohexol); EC 1.6.3.- (NADPH Oxidase 4)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180113
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191034


  2 / 970 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28922779
[Au] Autor:Hanley CJ; Mellone M; Ford K; Thirdborough SM; Mellows T; Frampton SJ; Smith DM; Harden E; Szyndralewiez C; Bullock M; Noble F; Moutasim KA; King EV; Vijayanand P; Mirnezami AH; Underwood TJ; Ottensmeier CH; Thomas GJ
[Ad] Endereço:Cancer Sciences Unit, University of Southampton Faculty of Medicine, Southampton, UK; Genkyotex SA, Plan-les-Ouates, Switzerland; La Jolla Institute for Allergy and Immunology, La Jolla, CA.
[Ti] Título:Targeting the Myofibroblastic Cancer-Associated Fibroblast Phenotype Through Inhibition of NOX4.
[So] Source:J Natl Cancer Inst;110(1), 2018 Jan 01.
[Is] ISSN:1460-2105
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: Cancer-associated fibroblasts (CAFs) are tumor-promoting and correlate with poor survival in many cancers, which has led to their emergence as potential therapeutic targets. However, effective methods to manipulate these cells clinically have yet to be developed. Methods: CAF accumulation and prognostic significance in head and neck cancer (oral, n = 260; oropharyngeal, n = 271), and colorectal cancer (n = 56) was analyzed using immunohistochemistry. Mechanisms regulating fibroblast-to-myofibroblast transdifferentiation were investigated in vitro using RNA interference/pharmacological inhibitors followed by polymerase chain reaction (PCR), immunoblotting, immunofluorescence, and functional assays. RNA sequencing/bioinformatics and immunohistochemistry were used to analyze NAD(P)H Oxidase-4 (NOX4) expression in different human tumors. NOX4's role in CAF-mediated tumor progression was assessed in vitro, using CAFs from multiple tissues in Transwell and organotypic culture assays, and in vivo, using xenograft (n = 9-15 per group) and isograft (n = 6 per group) tumor models. All statistical tests were two-sided. Results: Patients with moderate/high levels of myofibroblastic-CAF had a statistically significant decrease in cancer-specific survival rates in each cancer type analyzed (hazard ratios [HRs] = 1.69-7.25, 95% confidence intervals [CIs] = 1.11 to 31.30, log-rank P ≤ .01). Fibroblast-to-myofibroblast transdifferentiation was dependent on a delayed phase of intracellular reactive oxygen species, generated by NOX4, across different anatomical sites and differentiation stimuli. A statistically significant upregulation of NOX4 expression was found in multiple human cancers (P < .001), strongly correlating with myofibroblastic-CAFs (r = 0.65-0.91, adjusted P < .001). Genetic/pharmacological inhibition of NOX4 was found to revert the myofibroblastic-CAF phenotype ex vivo (54.3% decrease in α-smooth muscle actin [α-SMA], 95% CI = 10.6% to 80.9%, P = .009), prevent myofibroblastic-CAF accumulation in vivo (53.2%-79.0% decrease in α-SMA across different models, P ≤ .02) and slow tumor growth (30.6%-64.0% decrease across different models, P ≤ .04). Conclusions: These data suggest that pharmacological inhibition of NOX4 may have broad applicability for stromal targeting across cancer types.
[Mh] Termos MeSH primário: Adenocarcinoma/tratamento farmacológico
Fibroblastos Associados a Câncer/patologia
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico
Carcinoma de Células Escamosas/tratamento farmacológico
Neoplasias Colorretais/química
Neoplasias Esofágicas/tratamento farmacológico
Neoplasias Pulmonares/tratamento farmacológico
Neoplasias Bucais/química
Miofibroblastos/patologia
NADPH Oxidases/antagonistas & inibidores
Neoplasias Orofaríngeas/química
[Mh] Termos MeSH secundário: Actinas/análise
Adenocarcinoma/química
Adenocarcinoma/genética
Adulto
Idoso
Idoso de 80 Anos ou mais
Animais
Fibroblastos Associados a Câncer/química
Fibroblastos Associados a Câncer/fisiologia
Carcinoma Pulmonar de Células não Pequenas/química
Carcinoma Pulmonar de Células não Pequenas/genética
Carcinoma de Células Escamosas/química
Carcinoma de Células Escamosas/genética
Contagem de Células
Transdiferenciação Celular/efeitos dos fármacos
Transdiferenciação Celular/genética
Neoplasias Colorretais/patologia
Progressão da Doença
Neoplasias Esofágicas/química
Neoplasias Esofágicas/genética
Feminino
Neoplasias de Cabeça e Pescoço/química
Neoplasias de Cabeça e Pescoço/tratamento farmacológico
Neoplasias de Cabeça e Pescoço/genética
Seres Humanos
Neoplasias Pulmonares/química
Neoplasias Pulmonares/genética
Masculino
Camundongos
Meia-Idade
Neoplasias Bucais/patologia
Miofibroblastos/química
NADPH Oxidase 4
NADPH Oxidases/análise
NADPH Oxidases/genética
Transplante de Neoplasias
Neoplasias Orofaríngeas/patologia
Fenótipo
Pirazóis/uso terapêutico
Piridinas/uso terapêutico
Interferência de RNA
Espécies Reativas de Oxigênio/metabolismo
Taxa de Sobrevida
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ACTA2 protein, human); 0 (Actins); 0 (GKT137831); 0 (Pyrazoles); 0 (Pyridines); 0 (Reactive Oxygen Species); EC 1.6.3.- (NADPH Oxidase 4); EC 1.6.3.- (NADPH Oxidases); EC 1.6.3.- (NOX4 protein, human)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170920
[St] Status:MEDLINE
[do] DOI:10.1093/jnci/djx121


  3 / 970 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29208521
[Au] Autor:Bae D; Gautam J; Jang H; Banskota S; Lee SY; Jeong MJ; Kim AS; Kim HC; Lee IH; Nam TG; Kim JA; Jeong BS
[Ad] Endereço:College of Pharmacy and Institute for Drug Research, Yeungnam University, Gyeongsan 38541, Republic of Korea.
[Ti] Título:Protective effects of 6-ureido/thioureido-2,4,5-trimethylpyridin-3-ols against 4-hydroxynonenal-induced cell death in adult retinal pigment epithelial-19 cells.
[So] Source:Bioorg Med Chem Lett;28(2):107-112, 2018 01 15.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Dysfunction or progressive degeneration of retinal pigment epithelium (RPE) contributes in the initial pathogenesis of age-related macular degeneration (AMD) causing irreversible vision loss, which makes RPE the prime target of the disease. The present study aimed to identify compounds to protect 4-hydroxynonenal (4-HNE)-induced RPE cell death by inhibiting NADPH oxidase 4 (NOX4) activity, not just as free radical scavengers, using ARPE-19, a human adult retinal pigment epithelial cell line, as a RPE representative. Novel thirty-two 6-ureido/thioureido-2,4,5-trimethylpyridin-3-ol derivatives 17 were synthesized and tested. We found that there was a strong correlation between level of protective effect of compounds 17 against 4-HNE-induced APRE-19 cell death and that of inhibitory activity against 4-HNE-induced superoxide production, and that most of the compounds 17 showed minimal DPPH radical scavenging activity. Compound 17-28 showed the best protective activity against 4-HNE-induced superoxide production (79.5% inhibition) and cell death (85.1% recovery) at 10 µM concentration, which was better than that of VAS2870, a NOX2/4 inhibitor. In addition, compound 17-28 blocked 4-HNE-induced apoptosis of ARPE-19 cells in a concentration-dependent manner. The results indicate that compound 17-28 may be a lead compound to develop AMD therapeutics.
[Mh] Termos MeSH primário: Aldeídos/antagonistas & inibidores
Inibidores Enzimáticos/farmacologia
Piridinas/farmacologia
[Mh] Termos MeSH secundário: Adulto
Aldeídos/farmacologia
Morte Celular/efeitos dos fármacos
Linhagem Celular
Sobrevivência Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Inibidores Enzimáticos/síntese química
Inibidores Enzimáticos/química
Seres Humanos
Estrutura Molecular
NADPH Oxidase 4/antagonistas & inibidores
NADPH Oxidase 4/metabolismo
Piridinas/síntese química
Piridinas/química
Relação Estrutura-Atividade
Superóxidos/antagonistas & inibidores
Superóxidos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Aldehydes); 0 (Enzyme Inhibitors); 0 (Pyridines); 11062-77-4 (Superoxides); EC 1.6.3.- (NADPH Oxidase 4); EC 1.6.3.- (NOX4 protein, human); K1CVM13F96 (4-hydroxy-2-nonenal)
[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:171207
[St] Status:MEDLINE


  4 / 970 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29179217
[Au] Autor:Rozentsvit A; Vinokur K; Samuel S; Li Y; Gerdes AM; Carrillo-Sepulveda MA
[Ad] Endereço:Department of Biomedical Sciences, New York Institute of Technology, College of Osteopathic Medicine, Old Westbury, New York, USA.
[Ti] Título:Ellagic Acid Reduces High Glucose-Induced Vascular Oxidative Stress Through ERK1/2/NOX4 Signaling Pathway.
[So] Source:Cell Physiol Biochem;44(3):1174-1187, 2017.
[Is] ISSN:1421-9778
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIMS: Elevated production of reactive oxygen species (ROS) is linked to endothelial dysfunction and is one of the key contributors to the pathogenesis of diabetic vascular complications. Emerging evidence has indicated that ellagic acid (EA), a polyphenol found in fruits and nuts, possesses numerous biological activities including radical scavenging. However, whether EA exerts a vasculo-protective effect via antioxidant mechanisms in blood vessels exposed to diabetic conditions remains unknown. Accordingly, the goal of this current study was to determine whether EA decreases vascular ROS production and thus ameliorates endothelial dysfunction in the diabetic milieu. METHODS: Intact rat aortas and human aortic endothelial cells (HAEC) were stimulated with 30mM high glucose (HG) with and without EA co-treatment. Endothelium-dependent vasodilation was measured using a wire myograph. Gene and protein expression of non-phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidases 4 (NOX4) were detected using RT-PCR and western blotting, respectively. Oxidative stress was determined by measuring ROS levels using dihydroethidium (DHE) staining. RESULTS: Intact aortas exposed to HG condition displayed exacerbated ROS production and impairment of endothelium-dependent vasodilation, characterizing endothelial dysfunction. These effects were markedly reduced with EA treatment. HG enhanced ROS production in HAEC, paralleled by increased ERK1/2 activation and NOX4 expression. EA treatment blunted the increase of ROS generation, ERK1/2 activation and decreased NOX4. CONCLUSIONS: EA significantly decreases endothelial ROS levels and ameliorates the impairment of vascular relaxation induced by HG. Our results suggest that EA exerts a vasculo-protective effect under diabetic conditions via an antioxidant effect that involves inhibition of ERK1/2 and downregulation of NOX4.
[Mh] Termos MeSH primário: Aorta/efeitos dos fármacos
Ácido Elágico/farmacologia
Glucose/toxicidade
Estresse Oxidativo/efeitos dos fármacos
Transdução de Sinais/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Aorta/citologia
Aorta/metabolismo
Linhagem Celular
Ciclo-Oxigenase 2/metabolismo
Células Endoteliais/citologia
Células Endoteliais/efeitos dos fármacos
Células Endoteliais/metabolismo
Seres Humanos
Técnicas In Vitro
Masculino
Proteína Quinase 1 Ativada por Mitógeno/metabolismo
Proteína Quinase 3 Ativada por Mitógeno/metabolismo
NADPH Oxidase 4/metabolismo
Ratos
Ratos Sprague-Dawley
Espécies Reativas de Oxigênio/metabolismo
Vasodilatação/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Reactive Oxygen Species); 19YRN3ZS9P (Ellagic Acid); EC 1.14.99.1 (Cyclooxygenase 2); EC 1.6.3.- (NADPH Oxidase 4); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180118
[Lr] Data última revisão:
180118
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1159/000485448


  5 / 970 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27773825
[Au] Autor:García-Redondo AB; Aguado A; Briones AM; Salaices M
[Ad] Endereço:Departamento de Farmacología, Facultad de Medicina, Universidad Autónoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), 28029, Madrid, Spain.
[Ti] Título:NADPH oxidases and vascular remodeling in cardiovascular diseases.
[So] Source:Pharmacol Res;114:110-120, 2016 Dec.
[Is] ISSN:1096-1186
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Reactive oxygen species (ROS) are key signaling molecules that regulate vascular function and structure in physiological conditions. A misbalance between the production and detoxification of ROS increases oxidative stress that is involved in the vascular remodeling associated with cardiovascular diseases such as hypertension by affecting inflammation, hypertrophy, migration, growth/apoptosis and extracellular matrix protein turnover. The major and more specific source of ROS in the cardiovascular system is the NADPH oxidase (NOX) family of enzymes composed of seven members (NOX1-5, DUOX 1/2). Vascular cells express several NOXs being NOX-1 and NOX-4 the most abundant NOXs present in vascular smooth muscle cells. This review focuses on specific aspects of NOX-1 and NOX-4 isoforms including information on regulation, function and their role in vascular remodeling. In order to obtain a more integrated view about the role of the different NOX isoforms in different types of vascular remodeling, we discuss the available literature not only on hypertension but also in atherosclerosis, restenosis and aortic dilation.
[Mh] Termos MeSH primário: Doenças Cardiovasculares/enzimologia
Doenças Cardiovasculares/patologia
NADPH Oxidases/metabolismo
Remodelação Vascular
[Mh] Termos MeSH secundário: Animais
Doenças Cardiovasculares/metabolismo
Movimento Celular
Proliferação Celular
Seres Humanos
NADPH Oxidase 1/análise
NADPH Oxidase 1/metabolismo
NADPH Oxidase 4/análise
NADPH Oxidase 4/metabolismo
NADPH Oxidases/análise
Isoformas de Proteínas/análise
Isoformas de Proteínas/metabolismo
Espécies Reativas de Oxigênio/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Protein Isoforms); 0 (Reactive Oxygen Species); EC 1.6.3.- (NADPH Oxidase 1); EC 1.6.3.- (NADPH Oxidase 4); EC 1.6.3.- (NADPH Oxidases)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171226
[Lr] Data última revisão:
171226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161107
[St] Status:MEDLINE


  6 / 970 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29111459
[Au] Autor:Chen H; Song Z; Ying S; Yang X; Wu W; Tan Q; Ju X; Wu W; Zhang X; Qu J; Wang Y
[Ad] Endereço:Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China; The Eye Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
[Ti] Título:Myeloid differentiation protein 2 induced retinal ischemia reperfusion injury via upregulation of ROS through a TLR4-NOX4 pathway.
[So] Source:Toxicol Lett;282:109-120, 2018 Jan 05.
[Is] ISSN:1879-3169
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Retinal ischemia reperfusion (I/R) injury is common in many ophthalmic diseases. Recent studies have shown that toll-like receptor 4 (TLR4) is involved in ischemic retinal injury. Activation of TLRs requires specific accessory proteins such as myeloid differentiation protein 2 (MD2), which facilitate in ligand responsiveness. Therefore, inhibiting MD2 may be a novel approach to modulate TLR4 signaling and deleterious downstream effects in ischemic retinal injury. We used human Müller MIO-M1 cells treated with tert-butyl hydroperoxide (TBHP) to establish an in vitro I/R model of oxidative injury and tested the therapeutic effect of inhibiting MD2. Furthermore, we inhibited MD2 in a mouse model of retinal I/R injury and confirmed the results using MD2 knockout mice. Our studies show that pharmacological inhibition of MD2 prevented TBHP-induced reactive oxygen species (ROS) generation, inflammation and subsequent apoptosis in Müller cells. We also show that retinal I/R injury in mice induced functional deficits, increased ROS levels, inflammation and apoptosis. These pathological changes were not observed in MD2 knockout mice and attenuated when MD2 was inhibited in wildtype mice. In addition, we discovered that the mechanism of these therapeutic effects involved regulation of NADPH oxidase 4 (NOX4)-MD2-TLR4 complex formation. This study provides evidence that MD2 plays a key role in the pathogenesis of retinal I/R damage by participating in TLR4-NOX4 complex formation and elaboration of oxidative and inflammatory damage. Hence, inhibition of MD2 may reduce TLR-dependent damage during retinal I/R injury.
[Mh] Termos MeSH primário: Antígeno 96 de Linfócito/antagonistas & inibidores
NADPH Oxidase 4/metabolismo
Espécies Reativas de Oxigênio/metabolismo
Traumatismo por Reperfusão/metabolismo
Doenças Retinianas/metabolismo
Receptor 4 Toll-Like/metabolismo
[Mh] Termos MeSH secundário: Animais
Apoptose/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Chalconas/farmacologia
Modelos Animais de Doenças
Células Ependimogliais
Seres Humanos
Antígeno 96 de Linfócito/genética
Camundongos Endogâmicos C57BL
Camundongos Knockout
Estresse Oxidativo/efeitos dos fármacos
Transdução de Sinais
terc-Butil Hidroperóxido/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (1-(3,4-dihydroxyphenyl)-3-(2-methoxyphenyl)prop-2-en-1-one); 0 (Chalcones); 0 (Ly96 protein, mouse); 0 (Lymphocyte Antigen 96); 0 (Reactive Oxygen Species); 0 (Tlr4 protein, mouse); 0 (Toll-Like Receptor 4); 955VYL842B (tert-Butylhydroperoxide); EC 1.6.3.- (NADPH Oxidase 4); EC 1.6.3.- (Nox4 protein, mouse)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171201
[Lr] Data última revisão:
171201
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171108
[St] Status:MEDLINE


  7 / 970 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28890346
[Au] Autor:Li C; Li L; Yang CF; Zhong YJ; Wu D; Shi L; Chen L; Li YW
[Ad] Endereço:College of Pharmacy, Guilin Medical University, Guilin 541004, PR China.
[Ti] Título:Hepatoprotective effects of Methyl ferulic acid on alcohol-induced liver oxidative injury in mice by inhibiting the NOX4/ROS-MAPK pathway.
[So] Source:Biochem Biophys Res Commun;493(1):277-285, 2017 Nov 04.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:AIMS: The present study aimed to investigate the hepatoprotective effects of Methyl ferulic acid (MFA) against oxidative stress and apoptosis as well as inflammation in mice with liver injury induced by alcohol and its underlying mechanisms. METHODS: C57BL/6 mice were divided into a control group,a model group, and Methyl ferulic acid with high dosage (20 mg/kg), moderate dosage (10 mg/kg) and low dosage (5 mg/kg) groups. The general condition and organ index of each group were investigated. Histopathological analysis was performed to determine the degree of hepatic injury. Biochemical analyses of functional liver enzymes, lipid peroxidation enzymes and lipid content in each group. The levels of inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA). The mechanisms were investigated by detecting levels of NADPH Oxidase 4 (NOX4),p22phox, cytochrome P4502E1 (CYP2E1),Bax,B-cell lymphoma 2 (Bcl-2),cleaved-caspase 3 and 9 and phosphorylated extracellular regulated protein kinases(ERK),phosphorylated c-Jun N-terminal kinase (JNK), and phosphorylated p38 mitogen-activated protein kinase (MAPK) using real-time polymerase chain reaction (PCR) and Western blotting. RESULTS: MFA treatment significantly decreased serum enzymatic activities of alanine aminotransferase (ALT) and aspartate aminotransaminase (AST). MFA markedly increased levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GSH-Px) and total antioxidative capacity (T-AOC), and reduced the concentration of malondialdehyde (MDA) and reactive oxygen species (ROS). Histopathological examination of livers showed that MFA reduced cytoplasmic vacuolisation necrosis and inflammatory cell infiltration in alcohol-treated mice. MFA treatment remarkably reduced the levels of trigyceride (TG), total cholesterol (TC) and low-density lipoprotein (LDL), decreasing the levels of high-density lipoprotein (HDL), alcohol dehydrogenase(ADL) and aldehyde dehydrogenase (ALDH). MFA treatment remarkably inhibited the expression of inflammatory factors tumour necrosis factor (TNF)-α, monocyte chemoattractant protein 1 (MCP-1), interleukin (IL)-1ß and IL-6. MFA attenuated both mRNA and protein expression of NOX4,p22phox,CYP2E1,Bax/Bcl-2. In addition, MFA inhibited the activation of caspase 3 and 9 and downregulated the levels of p-JNK,p-p38 MAPK and p-ERK in liver. CONCLUSION: MFA has a protective effect on alcohol-induced liver injury, which may be related to its antioxidant,anti-inflammatory,lipid-eliminating properties and its ability to regulate the NOX4/ROS-MAPK signalling pathway.
[Mh] Termos MeSH primário: Ácidos Cafeicos/administração & dosagem
Hepatopatias Alcoólicas/tratamento farmacológico
Hepatopatias Alcoólicas/metabolismo
NADPH Oxidases/metabolismo
Estresse Oxidativo/efeitos dos fármacos
Espécies Reativas de Oxigênio/metabolismo
[Mh] Termos MeSH secundário: Animais
Antioxidantes/administração & dosagem
Doença Hepática Induzida por Substâncias e Drogas
Relação Dose-Resposta a Droga
Etanol
Hepatopatias Alcoólicas/patologia
Sistema de Sinalização das MAP Quinases/efeitos dos fármacos
Masculino
Camundongos
Camundongos Endogâmicos C57BL
NADPH Oxidase 4
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antioxidants); 0 (Caffeic Acids); 0 (Reactive Oxygen Species); 3K9958V90M (Ethanol); EC 1.6.3.- (NADPH Oxidase 4); EC 1.6.3.- (NADPH Oxidases); EC 1.6.3.- (Nox4 protein, mouse); Y98BUA66RX (methyl ferulate)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170912
[St] Status:MEDLINE


  8 / 970 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28771600
[Au] Autor:Nakamura K; Miura D; Saito Y; Yunoki K; Koyama Y; Satoh M; Kondo M; Osawa K; Hatipoglu OF; Miyoshi T; Yoshida M; Morita H; Ito H
[Ad] Endereço:Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
[Ti] Título:Eicosapentaenoic acid prevents arterial calcification in klotho mutant mice.
[So] Source:PLoS One;12(8):e0181009, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The klotho gene was identified as an "aging-suppressor" gene that accelerates arterial calcification when disrupted. Serum and vascular klotho levels are reduced in patients with chronic kidney disease, and the reduced levels are associated with arterial calcification. Intake of eicosapentaenoic acid (EPA), an n-3 fatty acid, reduces the risk of fatal coronary artery disease. However, the effects of EPA on arterial calcification have not been fully elucidated. The aim of this study was to determine the effect of EPA on arterial calcification in klotho mutant mice. METHODS AND RESULTS: Four-week-old klotho mutant mice and wild-type (WT) mice were given a diet containing 5% EPA (EPA food, klotho and WT: n = 12, each) or not containing EPA (control food, klotho and WT: n = 12, each) for 4 weeks. Calcium volume scores of thoracic and abdominal aortas assessed by computed tomography were significantly elevated in klotho mice after 4 weeks of control food, but they were not elevated in klotho mice after EPA food or in WT mice. Serum levels of EPA and resolvin E1, an active metabolite of EPA, in EPA food-fed mice were significantly increased compared to those in control food-fed mice. An oxidative stress PCR array followed by quantitative PCR revealed that NADPH oxidase-4 (NOX4), an enzyme that generates superoxide, gene expression was up-regulated in arterial smooth muscle cells (SMCs) of klotho mice. Activity of NOX was also significantly higher in SMCs of klotho mice than in those of WT mice. EPA decreased expression levels of the NOX4 gene and NOX activity. GPR120, a receptor of n-3 fatty acids, gene knockdown by siRNA canceled effects of EPA on NOX4 gene expression and NOX activity in arterial SMCs of klotho mice. CONCLUSIONS: EPA prevents arterial calcification together with reduction of NOX gene expression and activity via GPR120 in klotho mutant mice.
[Mh] Termos MeSH primário: Artérias/efeitos dos fármacos
Calcinose/genética
Calcinose/prevenção & controle
Ácido Eicosapentaenoico/farmacologia
Glucuronidase/genética
Mutação
[Mh] Termos MeSH secundário: Animais
Ácido Araquidônico/sangue
Artérias/metabolismo
Calcinose/sangue
Calcinose/metabolismo
Cálcio/sangue
Cálcio/metabolismo
Ácido Eicosapentaenoico/análogos & derivados
Ácido Eicosapentaenoico/sangue
Feminino
Regulação da Expressão Gênica/efeitos dos fármacos
Masculino
Camundongos
NADPH Oxidase 4
NADPH Oxidases/metabolismo
Fósforo/sangue
Receptores Acoplados a Proteínas-G/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid); 0 (O3far1 protein, mouse); 0 (Receptors, G-Protein-Coupled); 27YG812J1I (Arachidonic Acid); 27YLU75U4W (Phosphorus); AAN7QOV9EA (Eicosapentaenoic Acid); EC 1.6.3.- (NADPH Oxidase 4); EC 1.6.3.- (NADPH Oxidases); EC 1.6.3.- (Nox4 protein, mouse); EC 3.2.1.31 (Glucuronidase); EC 3.2.1.31 (klotho protein); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170804
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0181009


  9 / 970 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28751569
[Au] Autor:Yu B; Liu Z; Fu Y; Wang Y; Zhang L; Cai Z; Yu F; Wang X; Zhou J; Kong W
[Ad] Endereço:From the Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, P. R. China (B.Y., Z.L., Y.F., Y.W., L.Z., Z.C., F.Y., X.W., W.K.); Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, P. R. China (B.Y., Z.L., Y.F.,
[Ti] Título:CYLD Deubiquitinates Nicotinamide Adenine Dinucleotide Phosphate Oxidase 4 Contributing to Adventitial Remodeling.
[So] Source:Arterioscler Thromb Vasc Biol;37(9):1698-1709, 2017 Sep.
[Is] ISSN:1524-4636
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Transdifferentiation of adventitial fibroblasts (AFs) into myofibroblasts plays a critical role during the vascular remodeling that occurs during atherosclerosis, restenosis, and aortic aneurysm. The ubiquitination/deubiquitination regulatory system is essential for the quality control of proteins. The involvement of ubiquitination/deubiquitination during AF transdifferentiation remains largely unknown. In this study, we determined the role of cylindromatosis (CYLD), a deubiquitinase, in the process of AF differentiation and activation in vitro and in vivo. APPROACH AND RESULTS: Transforming growth factor-ß1 and homocysteine, 2 known inducers of AF transdifferentiation, greatly upregulated CYLD expression in a time- and dose-dependent manner. The silencing of CYLD significantly inhibited AF transdifferentiation and activation as evidenced by the expression of contractile proteins, the production of the proinflammatory cytokines MCP-1 (monocyte chemotactic protein 1) and IL-6 (interleukin-6), the deposition of extracellular matrix, and cell migration. We further asked whether CYLD mediates AF activation via the regulation of nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) as it is an essential factor during AF transdifferentiation. Indeed, the silencing of CYLD repressed transforming growth factor-ß1-induced and homocysteine-induced Nox4 upregulation and reactive oxygen species production, whereas Nox4 overexpression greatly rescued the inhibitory effect on AF activation by CYLD silencing. Most interestingly, transforming growth factor-ß1 and homocysteine repressed Nox4 ubiquitination and prolonged the half-life of Nox4. Moreover, Nox4 was deubiquitinated via a direct interaction with the ubiquitin-specific protease domain of CYLD. In accordance, hyperhomocysteinemia significantly increased adventitial CYLD and Nox4 expression, promoted AF transdifferentiation, and aggravated CaPO -induced abdominal aortic aneurysm in mice. These effects were abolished in CYLD mice. CONCLUSIONS: CYLD contributes to the transdifferentiation of AFs via deubiquitinating Nox4 and may play a role in vascular remodeling.
[Mh] Termos MeSH primário: Túnica Adventícia/enzimologia
Aneurisma da Aorta Abdominal/enzimologia
Transdiferenciação Celular
Cisteína Endopeptidases/metabolismo
Miofibroblastos/enzimologia
NADPH Oxidases/metabolismo
Ubiquitina Tiolesterase/metabolismo
Remodelação Vascular
[Mh] Termos MeSH secundário: Túnica Adventícia/efeitos dos fármacos
Túnica Adventícia/patologia
Animais
Aneurisma da Aorta Abdominal/induzido quimicamente
Aneurisma da Aorta Abdominal/genética
Aneurisma da Aorta Abdominal/patologia
Células COS
Fosfatos de Cálcio
Movimento Celular
Transdiferenciação Celular/efeitos dos fármacos
Cercopithecus aethiops
Quimiocina CCL2/metabolismo
Cisteína Endopeptidases/deficiência
Cisteína Endopeptidases/genética
Modelos Animais de Doenças
Relação Dose-Resposta a Droga
Estabilidade Enzimática
Matriz Extracelular/metabolismo
Genótipo
Células HEK293
Meia-Vida
Homocisteína/farmacologia
Seres Humanos
Hiper-Homocisteinemia/complicações
Hiper-Homocisteinemia/enzimologia
Hiper-Homocisteinemia/genética
Interleucina-6/metabolismo
Masculino
Camundongos Endogâmicos C57BL
Camundongos Knockout
Miofibroblastos/efeitos dos fármacos
Miofibroblastos/patologia
NADPH Oxidase 4
NADPH Oxidases/genética
Fenótipo
Proteólise
Interferência de RNA
Ratos Sprague-Dawley
Espécies Reativas de Oxigênio/metabolismo
Transdução de Sinais
Fatores de Tempo
Transfecção
Fator de Crescimento Transformador beta1/farmacologia
Ubiquitina Tiolesterase/genética
Ubiquitinação
Remodelação Vascular/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calcium Phosphates); 0 (Ccl2 protein, mouse); 0 (Chemokine CCL2); 0 (Interleukin-6); 0 (Reactive Oxygen Species); 0 (Transforming Growth Factor beta1); 0 (interleukin-6, mouse); 0LVT1QZ0BA (Homocysteine); 97Z1WI3NDX (calcium phosphate); EC 1.6.3.- (NADPH Oxidase 4); EC 1.6.3.- (NADPH Oxidases); EC 1.6.3.- (Nox4 protein, mouse); EC 1.6.3.- (Nox4 protein, rat); EC 3.4.19.12 (CYLD protein, mouse); EC 3.4.19.12 (CYLD protein, rat); EC 3.4.19.12 (Ubiquitin Thiolesterase); EC 3.4.22.- (Cysteine Endopeptidases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170729
[St] Status:MEDLINE
[do] DOI:10.1161/ATVBAHA.117.309859


  10 / 970 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28723216
[Au] Autor:Jhou BY; Song TY; Lee I; Hu ML; Yang NC
[Ad] Endereço:Department of Food Science and Biotechnology, National Chung Hsing University , Taichung, Taiwan.
[Ti] Título:Lycopene Inhibits Metastasis of Human Liver Adenocarcinoma SK-Hep-1 Cells by Downregulation of NADPH Oxidase 4 Protein Expression.
[So] Source:J Agric Food Chem;65(32):6893-6903, 2017 Aug 16.
[Is] ISSN:1520-5118
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:NADPH oxidase 4 (NOX4), with the sole function to produce reactive oxygen species (ROS), can be a molecular target for disrupting cancer metastasis. Several studies have indicated that lycopene exhibited anti-metastatic actions in vitro and in vivo. However, the role of NOX4 in the anti-metastatic action of lycopene remains unknown. Herein, we first confirmed the anti-metastatic effect of lycopene (0.1-5 µM) on human liver adenocarcinoma SK-Hep-1 cells. We showed that lycopene significantly inhibited NOX4 protein expression, with the strongest inhibition of 64.3 ± 10.2% (P < 0.05) at 2.5 µM lycopene. Lycopene also significantly inhibited NOX4 mRNA expression, NOX activity, and intracellular ROS levels in SK-Hep-1 cells. We then determined the effects of lycopene on transforming growth factor ß (TGF-ß)-induced metastasis. We found that TGF-ß (5 ng/mL) significantly increased migration, invasion, and adhesion activity, the intracellular ROS level, matrix metalloproteinase 9 (MMP-9) and MMP-2 activities, the level of NOX4 protein expression, and NOX activity. All these TGF-ß-induced effects were antagonized by the incubation of SK-Hep-1 cells with lycopene (2.5 µM). Using transient transfection of siRNA against NOX4, we found that the downregulation of NOX4 could mimic lycopene by inhibiting cell migration and the activities of MMP-9 and MMP-2 during the incubation with or without TGF-ß on SK-Hep-1 cells. The results demonstrate that the downregulation of NOX4 plays a crucial role in the anti-metastatic action of lycopene in SK-Hep-1 cells.
[Mh] Termos MeSH primário: Adenocarcinoma/enzimologia
Carotenoides/farmacologia
Neoplasias Hepáticas/enzimologia
NADPH Oxidases/genética
[Mh] Termos MeSH secundário: Adenocarcinoma/tratamento farmacológico
Adenocarcinoma/genética
Linhagem Celular Tumoral
Regulação para Baixo/efeitos dos fármacos
Seres Humanos
Neoplasias Hepáticas/tratamento farmacológico
Neoplasias Hepáticas/genética
Metaloproteinase 2 da Matriz/genética
Metaloproteinase 2 da Matriz/metabolismo
Metaloproteinase 9 da Matriz/genética
Metaloproteinase 9 da Matriz/metabolismo
NADPH Oxidase 4
NADPH Oxidases/metabolismo
Espécies Reativas de Oxigênio/metabolismo
Fator de Crescimento Transformador beta/genética
Fator de Crescimento Transformador beta/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Reactive Oxygen Species); 0 (Transforming Growth Factor beta); 36-88-4 (Carotenoids); EC 1.6.3.- (NADPH Oxidase 4); EC 1.6.3.- (NADPH Oxidases); EC 1.6.3.- (NOX4 protein, human); EC 3.4.24.24 (Matrix Metalloproteinase 2); EC 3.4.24.35 (Matrix Metalloproteinase 9); SB0N2N0WV6 (lycopene)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170721
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jafc.7b03036



página 1 de 97 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