Base de dados : MEDLINE
Pesquisa : D08.811.682.690.416.617 [Categoria DeCS]
Referências encontradas : 121 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 13 ir para página                         

  1 / 121 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
[PMID]:29277791
[Au] Autor:Bur H; Haapasaari KM; Turpeenniemi-Hujanen T; Kuittinen O; Auvinen P; Marin K; Soini Y; Karihtala P
[Ad] Endereço:Department of Oncology and Radiotherapy, Medical Research Center Oulu, Oulu University Hospital, Oulu, Finland.
[Ti] Título:Strong Prolyl Hydroxylase Domain 1 Expression Predicts Poor Outcome in Radiotherapy-treated Patients with Classical Hodgkin's Lymphoma.
[So] Source:Anticancer Res;38(1):329-336, 2018 01.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Hypoxia-inducible factors (HIFs) and prolyl hydroxylase domain (PHD) proteins control cellular oxygen homeostasis and a wide range of other processes. MATERIALS AND METHODS: We immunohistochemically assessed the expression of HIF1α, HIF2α, PHD1, PHD2 and PHD3 in 115 cases of classical Hodgkin's lymphoma, all treated in the first line with doxorubicin, bleomycin, vinblastine and darcabazine (ABVD) chemotherapy. RESULTS: In advanced-stage patients treated with involved-field radiotherapy (IFRT), nuclear HIF1α expression in reactive cellular infiltrate predicted prolonged relapse-free survival (RFS) (p=0.026). Strong cytoplasmic PHD1 expression in Reed-Sternberg cells was associated with poor RFS among patients treated with IFRT and advanced-stage patients treated with ABVD and IFRT (p=0.0028 and p=0.0058, respectively). In Cox regression analysis, PHD1 was a more significant predictor of relapse (risk ratio=18.383; 95% confidence interval(CI)=1.521-222.246; p=0.022) than the International Prognostic Score. CONCLUSION: HIF and PHD expression appear to be novel prognostic biomarkers in classical Hodgkin's lymphoma.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/biossíntese
Doença de Hodgkin/patologia
Doença de Hodgkin/radioterapia
Prolil Hidroxilases/biossíntese
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Idoso de 80 Anos ou mais
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Fatores de Transcrição Hélice-Alça-Hélice Básicos/biossíntese
Bleomicina/uso terapêutico
Hipóxia Celular/fisiologia
Dacarbazina/uso terapêutico
Doxorrubicina/uso terapêutico
Feminino
Doença de Hodgkin/tratamento farmacológico
Doença de Hodgkin/mortalidade
Seres Humanos
Subunidade alfa do Fator 1 Induzível por Hipóxia/biossíntese
Prolina Dioxigenases do Fator Induzível por Hipóxia/biossíntese
Masculino
Meia-Idade
Estudos Retrospectivos
Resultado do Tratamento
Vimblastina/uso terapêutico
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Basic Helix-Loop-Helix Transcription Factors); 0 (Biomarkers, Tumor); 0 (HIF1A protein, human); 0 (Hypoxia-Inducible Factor 1, alpha Subunit); 0 (endothelial PAS domain-containing protein 1); 11056-06-7 (Bleomycin); 5V9KLZ54CY (Vinblastine); 7GR28W0FJI (Dacarbazine); 80168379AG (Doxorubicin); EC 1.14.11.- (Prolyl Hydroxylases); EC 1.14.11.2 (EGLN1 protein, human); EC 1.14.11.29 (EGLN2 protein, human); EC 1.14.11.29 (EGLN3 protein, human); EC 1.14.11.29 (Hypoxia-Inducible Factor-Proline Dioxygenases)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180104
[Lr] Data última revisão:
180104
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171227
[St] Status:MEDLINE


  2 / 121 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28981257
[Au] Autor:Schnicker NJ; Razzaghi M; Guha Thakurta S; Chakravarthy S; Dey M
[Ad] Endereço:Department of Chemistry, The University of Iowa , Iowa City, Iowa 52242, United States.
[Ti] Título:Bacillus anthracis Prolyl 4-Hydroxylase Interacts with and Modifies Elongation Factor Tu.
[So] Source:Biochemistry;56(43):5771-5785, 2017 Oct 31.
[Is] ISSN:1520-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Prolyl hydroxylation is a very common post-translational modification and plays many roles in eukaryotes such as collagen stabilization, hypoxia sensing, and controlling protein transcription and translation. There is a growing body of evidence that suggests that prokaryotes contain prolyl 4-hydroxylases (P4Hs) homologous to the hypoxia-inducible factor (HIF) prolyl hydroxylase domain (PHD) enzymes that act on elongation factor Tu (EFTu) and are likely involved in the regulation of bacterial translation. Recent biochemical and structural studies with a PHD from Pseudomonas putida (PPHD) determined that it forms a complex with EFTu and hydroxylates a prolyl residue of EFTu. Moreover, while animal, plant, and viral P4Hs act on peptidyl proline, most prokaryotic P4Hs have been known to target free l-proline; the exceptions include PPHD and a P4H from Bacillus anthracis (BaP4H) that modifies collagen-like proline-rich peptides. Here we use biophysical and mass spectrometric methods to demonstrate that BaP4H recognizes full-length BaEFTu and a BaEFTu 9-mer peptide for site-specific proline hydroxylation. Using size-exclusion chromatography coupled small-angle X-ray scattering (SEC-SAXS) and binding studies, we determined that BaP4H forms a 1:1 heterodimeric complex with BaEFTu. The SEC-SAXS studies reveal dissociation of BaP4H dimeric subunits upon interaction with BaEFTu. While BaP4H is unusual within bacteria in that it is structurally and functionally similar to the animal PHDs and collagen P4Hs, respectively, this work provides further evidence of its promiscuous substrate recognition. It is possible that the enzyme might have evolved to hydroxylate a universally conserved protein in prokaryotes, similar to the PHDs, and implies a functional role in B. anthracis.
[Mh] Termos MeSH primário: Bacillus anthracis/metabolismo
Proteínas de Bactérias/metabolismo
Fator Tu de Elongação de Peptídeos/metabolismo
Prolil Hidroxilases/metabolismo
[Mh] Termos MeSH secundário: Bacillus anthracis/química
Bacillus anthracis/genética
Proteínas de Bactérias/química
Proteínas de Bactérias/genética
Fator Tu de Elongação de Peptídeos/química
Fator Tu de Elongação de Peptídeos/genética
Prolil Hidroxilases/química
Prolil Hidroxilases/genética
Ligação Proteica
Domínios Proteicos
Difração de Raios X
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); EC 1.14.11.- (Prolyl Hydroxylases); EC 3.6.1.- (Peptide Elongation Factor Tu)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171103
[Lr] Data última revisão:
171103
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171006
[St] Status:MEDLINE
[do] DOI:10.1021/acs.biochem.7b00601


  3 / 121 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28880966
[Au] Autor:Zhou J; Li J; Rosenbaum DM; Zhuang J; Poon C; Qin P; Rivera K; Lepore J; Willette RN; Hu E; Barone FC
[Ad] Endereço:Department of Neurology, State University of New York Downstate Medical Center, Brooklyn, New York, United States of America.
[Ti] Título:The prolyl 4-hydroxylase inhibitor GSK360A decreases post-stroke brain injury and sensory, motor, and cognitive behavioral deficits.
[So] Source:PLoS One;12(9):e0184049, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:There is interest in pharmacologic preconditioning for end-organ protection by targeting the HIF system. This can be accomplished by inhibition of prolyl 4-hydroxylase (PHD). GSK360A is an orally active PHD inhibitor that has been previously shown to protect the failing heart. We hypothesized that PHD inhibition can also protect the brain from injuries and resulting behavioral deficits that can occur as a result of surgery. Thus, our goal was to investigate the effect of pre-stroke surgery brain protection using a verified GSK360A PHD inhibition paradigm on post-stroke surgery outcomes. Vehicle or an established protective dose (30 mg/kg, p.o.) of GSK360A was administered to male Sprague-Dawley rats. Initially, GSK360A pharmacokinetics and organ distribution were determined, and then PHD-HIF pharmacodynamic markers were measured (i.e., to validate the pharmacological effects of the GSK360A administration regimen). Results obtained using this validated PHD dose-regimen indicated significant improvement by GSK360A (30mg/kg); administered at 18 and 5 hours prior to transient middle cerebral artery occlusion (stroke). GSK360A exposure and plasma, kidney and brain HIF-PHD pharmacodynamics endpoints (e.g., erythropoietin; EPO and Vascular Endothelial Growth Factor; VEGF) were measured. GSK360A provided rapid exposure in plasma (7734 ng/ml), kidney (45-52% of plasma level) and brain (1-4% of plasma level), and increased kidney EPO mRNA (80-fold) and brain VEGF mRNA (2-fold). We also observed that GSK360A increased plasma EPO (300-fold) and VEGF (2-fold). Further assessments indicated that GSK360A reduced post-stroke surgery neurological deficits (47-64%), cognitive dysfunction (60-75%) and brain infarction (30%) 4 weeks later. Thus, PHD inhibition using GSK360A pretreatment produced long-term post-stroke brain protection and improved behavioral functioning. These data support PHD inhibition, specifically by GSK360A, as a potential strategy for pre-surgical use to reduce brain injury and functional decline due to surgery-related cerebral injury.
[Mh] Termos MeSH primário: Comportamento Animal
Lesões Encefálicas/tratamento farmacológico
Lesões Encefálicas/etiologia
Transtornos Cognitivos/tratamento farmacológico
Glicina/análogos & derivados
Atividade Motora
Inibidores de Prolil-Hidrolase/uso terapêutico
Quinolonas/uso terapêutico
Acidente Vascular Cerebral/complicações
[Mh] Termos MeSH secundário: Administração Oral
Animais
Comportamento Animal/efeitos dos fármacos
Encéfalo/efeitos dos fármacos
Encéfalo/metabolismo
Encéfalo/patologia
Lesões Encefálicas/sangue
Lesões Encefálicas/fisiopatologia
Transtornos Cognitivos/etiologia
Eritropoetina/sangue
Eritropoetina/genética
Glicina/administração & dosagem
Glicina/farmacocinética
Glicina/farmacologia
Glicina/uso terapêutico
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo
Infarto da Artéria Cerebral Média/sangue
Infarto da Artéria Cerebral Média/complicações
Infarto da Artéria Cerebral Média/patologia
Infarto da Artéria Cerebral Média/fisiopatologia
Masculino
Atividade Motora/efeitos dos fármacos
Especificidade de Órgãos/efeitos dos fármacos
Prolil Hidroxilases/metabolismo
Inibidores de Prolil-Hidrolase/administração & dosagem
Inibidores de Prolil-Hidrolase/farmacologia
Quinolonas/administração & dosagem
Quinolonas/farmacocinética
Quinolonas/farmacologia
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Ratos Sprague-Dawley
Sensação/efeitos dos fármacos
Acidente Vascular Cerebral/sangue
Acidente Vascular Cerebral/fisiopatologia
Fator A de Crescimento do Endotélio Vascular/sangue
Fator A de Crescimento do Endotélio Vascular/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hypoxia-Inducible Factor 1, alpha Subunit); 0 (N-((1-(cyclopropylethyl)-6-fluoro-4-hydroxy-2-oxo-1,2-dihydro-3-quinolinyl)carbonyl)glycine); 0 (Prolyl-Hydroxylase Inhibitors); 0 (Quinolones); 0 (RNA, Messenger); 0 (Vascular Endothelial Growth Factor A); 11096-26-7 (Erythropoietin); EC 1.14.11.- (Prolyl Hydroxylases); TE7660XO1C (Glycine)
[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:170908
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184049


  4 / 121 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28610954
[Au] Autor:Chang YC; Chan YC; Chang WM; Lin YF; Yang CJ; Su CY; Huang MS; Wu ATH; Hsiao M
[Ad] Endereço:Graduate Institute of Life Sciences, National Defense Medical Center, Taiwan; Genomics Research Center, Academia Sinica, Taipei, Taiwan.
[Ti] Título:Feedback regulation of ALDOA activates the HIF-1α/MMP9 axis to promote lung cancer progression.
[So] Source:Cancer Lett;403:28-36, 2017 Sep 10.
[Is] ISSN:1872-7980
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Distant metastasis and recurrence are the greatest challenges in the clinical management of lung cancer. Despite advances in targeted therapies, high mortality rates persist. Therefore, alternative therapeutic interventions are urgently required. Accumulating evidence indicates that normalizing tumor metabolism may be a way to increase therapeutic efficacy and to reduce tumor malignancy. Here, we analyzed integrated transcriptomics data and an shRNA library against glycolytic enzymes and found that elevated Aldolase A expression is highly correlated with metastatic potential and a poor prognosis in patients with non-small cell lung cancer (NSCLC). We validated our in silico findings with an immunohistochemical analysis of clinical samples. Aldolase A silencing significantly suppressed metastatic potential both in vitro and in vivo, whereas the ectopic overexpression of Aldolase A resulted in the opposite phenotype. Furthermore, our microarray and Ingenuity Pathway Analyses (IPA) revealed that Aldolase A-driven lung cancer metastasis was closely linked to hypoxia inducible factor 1 alpha (HIF-1α)-downstream signaling. Importantly, Aldolase A overexpression may promote the release of lactate to block PHD activities and further induce HIF-1α stabilization. Aldolase A and nuclear HIF-1α overexpression levels were positively correlated and were significantly associated with a poorer survival rate in lung cancer patients (P = 0.008 for Overall Survival, P = 0.021 for Disease-free Survival). Furthermore, MMP9, a downstream target of HIF-1α, was significantly upregulated after ALDOA overexpression. A MMP9 inhibitor significantly inhibited cell invasion and migration in ALDOA-HIF-1α axis-induced lung cancer. In summary, our results reveal the molecular mechanism of Aldolase A in promoting lung cancer metastasis via PHD-mediated stabilization of HIF-1α and the subsequent activation of MMP9. The ALDOA-HIF-1α axis may provide a new therapeutic target for metastatic lung cancer treatment.
[Mh] Termos MeSH primário: Carcinoma Pulmonar de Células não Pequenas/enzimologia
Movimento Celular
Frutose-Bifosfato Aldolase/metabolismo
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo
Neoplasias Pulmonares/enzimologia
Metaloproteinase 9 da Matriz/metabolismo
[Mh] Termos MeSH secundário: Idoso
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico
Carcinoma Pulmonar de Células não Pequenas/genética
Carcinoma Pulmonar de Células não Pequenas/patologia
Linhagem Celular Tumoral
Movimento Celular/efeitos dos fármacos
Progressão da Doença
Intervalo Livre de Doença
Ativação Enzimática
Feminino
Frutose-Bifosfato Aldolase/genética
Perfilação da Expressão Gênica/métodos
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Hidroxilação
Subunidade alfa do Fator 1 Induzível por Hipóxia/genética
Estimativa de Kaplan-Meier
Neoplasias Pulmonares/tratamento farmacológico
Neoplasias Pulmonares/genética
Neoplasias Pulmonares/patologia
Masculino
Inibidores de Metaloproteinases de Matriz/farmacologia
Meia-Idade
Invasividade Neoplásica
Prolil Hidroxilases/metabolismo
Modelos de Riscos Proporcionais
Estabilidade Proteica
Proteólise
Interferência de RNA
Estudos Retrospectivos
Transdução de Sinais
Fatores de Tempo
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (HIF1A protein, human); 0 (Hypoxia-Inducible Factor 1, alpha Subunit); 0 (Matrix Metalloproteinase Inhibitors); EC 1.14.11.- (Prolyl Hydroxylases); EC 3.4.24.35 (MMP9 protein, human); EC 3.4.24.35 (Matrix Metalloproteinase 9); EC 4.1.2.13 (ALDOA protein, human); EC 4.1.2.13 (Fructose-Bisphosphate Aldolase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170615
[St] Status:MEDLINE


  5 / 121 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28592436
[Au] Autor:Hughes FM; Sexton SJ; Jin H; Govada V; Purves JT
[Ad] Endereço:Division of Urology, Department of Surgery, Duke University Medical Center, Durham, North Carolina; monty.hughes@duke.edu.
[Ti] Título:Bladder fibrosis during outlet obstruction is triggered through the NLRP3 inflammasome and the production of IL-1ß.
[So] Source:Am J Physiol Renal Physiol;313(3):F603-F610, 2017 Sep 01.
[Is] ISSN:1522-1466
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Bladder outlet obstruction (BOO) triggers inflammation in the bladder through the NLRP3 inflammasome. BOO also activates fibrosis, which is largely responsible for the decompensation of the bladder in the chronic state. Because fibrosis can be driven by inflammation, we have explored a role for NLRP3 (and IL-1ß produced by NLRP3) in the activation and progression of BOO-induced fibrosis. Female rats were divided into five groups: ) control, ) sham, ) BOO + vehicle, ) BOO + the NLRP3 inhibitor glyburide, or ) BOO + the IL-1ß receptor antagonist anakinra. Fibrosis was assessed by Masson's trichrome stain, collagen secretion via Sirius Red, and protein localization by immunofluorescence. BOO increased collagen production in the bladder, which was blocked by glyburide and anakinra, clearly implicating the NLRP3/IL-1ß pathway in fibrosis. The collagen was primarily found in the lamina propria and the smooth muscle, while IL-1 receptor 1 and prolyl 4-hydroylase (an enzyme involved in the intracellular modification of collagen) both localized to the urothelium and the smooth muscle. Lysyl oxidase, the enzyme involved in the final extracellular assembly of mature collagen fibrils, was found to some extent in the lamina propria where its expression was greatly enhanced during BOO. In vitro studies demonstrated isolated urothelial cells from BOO rats secreted substantially more collagen than controls, and collagen expression in control cultures could be directly stimulated by IL-1ß. In summary, NLRP3-derived-IL-1ß triggers fibrosis during BOO, most likely through an autocrine loop in which IL-1ß acts on urothelia to drive collagen production.
[Mh] Termos MeSH primário: Inflamassomos/metabolismo
Interleucina-1beta/metabolismo
Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo
Obstrução do Colo da Bexiga Urinária/metabolismo
Bexiga Urinária/metabolismo
[Mh] Termos MeSH secundário: Animais
Comunicação Autócrina
Células Cultivadas
Modelos Animais de Doenças
Feminino
Colágenos Fibrilares/metabolismo
Fibrose
Glibureto/farmacologia
Inflamassomos/antagonistas & inibidores
Proteína Antagonista do Receptor de Interleucina 1/farmacologia
Interleucina-1beta/antagonistas & inibidores
Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores
Prolil Hidroxilases/metabolismo
Proteína-Lisina 6-Oxidase/metabolismo
Ratos Sprague-Dawley
Receptores de Interleucina-1/antagonistas & inibidores
Receptores de Interleucina-1/metabolismo
Transdução de Sinais
Bexiga Urinária/efeitos dos fármacos
Bexiga Urinária/patologia
Obstrução do Colo da Bexiga Urinária/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fibrillar Collagens); 0 (IL1B protein, rat); 0 (Inflammasomes); 0 (Interleukin 1 Receptor Antagonist Protein); 0 (Interleukin-1beta); 0 (NLR Family, Pyrin Domain-Containing 3 Protein); 0 (Nlrp3 protein, rat); 0 (Receptors, Interleukin-1); EC 1.14.11.- (Prolyl Hydroxylases); EC 1.4.3.13 (Protein-Lysine 6-Oxidase); SX6K58TVWC (Glyburide)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171005
[Lr] Data última revisão:
171005
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170609
[St] Status:MEDLINE
[do] DOI:10.1152/ajprenal.00128.2017


  6 / 121 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28589291
[Au] Autor:Shi J; Ma X; Gao Y; Fan D; Zhu C; Mi Y; Xue W
[Ad] Endereço:Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi'an, 710069, Shaanxi, China.
[Ti] Título:Hydroxylation of Human Type III Collagen Alpha Chain by Recombinant Coexpression with a Viral Prolyl 4-Hydroxylase in Escherichia coli.
[So] Source:Protein J;36(4):322-331, 2017 Aug.
[Is] ISSN:1875-8355
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:High-level expression of recombinant collagen by genetic engineering is urgently required. Recombinant collagen is different from natural collagen in its hydroxyproline (Hyp) content and thermal stability. To obtain hydroxylated collagen for applications in biomedicine and biomaterials, the human collagen α1(III) chain was co-expressed with the viral prolyl 4-hydroxylase A085R in Escherichia coli. Unlike previous reports using human prolyl 4-hydroxylase, this study examined the hydroxylation of full-length human collagen α1(III) chain (COL3A1) by viral prolyl 4-hydroxylase. The genes encoding these two proteins were controlled by different promoters, Ptac and PRPL, on a recombinant pKK223-3 plasmid. The sequencing results verified that the target genes were successfully inserted into the recombinant vector. Based on quantitative PCR, SDS-PAGE, and western blotting, successful expression by E. coli BL21(DE3) was detected at the mRNA and protein levels for both loci. Liquid chromatography-mass spectrometry (LC-MS/MS) results suggested that the highest Hyp yield was obtained when the two proteins were induced with 0.5 mM IPTG and heat-shock treatment at 50 °C, corresponding to high enzyme expression and low human collagen α1(III) chain expression levels. A biological activity analysis indicated that the recombinant collagen with the highest hydroxylation level supported the growth of baby hamster kidney cells, similar to observations for native collagen. The production of hydroxylated collagen in this study establishes a new method for collagen hydroxylation and provides a basis for the application of recombinant collagen expressed in E. coli.
[Mh] Termos MeSH primário: Colágeno Tipo III/metabolismo
Escherichia coli/metabolismo
Plasmídeos/metabolismo
Prolil Hidroxilases/metabolismo
Proteínas Recombinantes/metabolismo
Proteínas Virais/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Linhagem Celular
Proliferação Celular/efeitos dos fármacos
Colágeno Tipo III/química
Colágeno Tipo III/genética
Colágeno Tipo III/farmacologia
Cricetinae
Escherichia coli/genética
Expressão Gênica
Seres Humanos
Hidroxilação
Phycodnaviridae/química
Phycodnaviridae/enzimologia
Plasmídeos/química
Prolil Hidroxilases/genética
Regiões Promotoras Genéticas
Proteínas Recombinantes/química
Proteínas Recombinantes/genética
Proteínas Recombinantes/farmacologia
Alinhamento de Sequência
Transformação Bacteriana
Proteínas Virais/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (COL3A1 protein, human); 0 (Collagen Type III); 0 (Recombinant Proteins); 0 (Viral Proteins); EC 1.14.11.- (Prolyl Hydroxylases)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170728
[Lr] Data última revisão:
170728
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170608
[St] Status:MEDLINE
[do] DOI:10.1007/s10930-017-9723-0


  7 / 121 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28436951
[Au] Autor:Hsu YL; Hung JY; Chang WA; Lin YS; Pan YC; Tsai PH; Wu CY; Kuo PL
[Ad] Endereço:Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
[Ti] Título:Hypoxic lung cancer-secreted exosomal miR-23a increased angiogenesis and vascular permeability by targeting prolyl hydroxylase and tight junction protein ZO-1.
[So] Source:Oncogene;36(34):4929-4942, 2017 Aug 24.
[Is] ISSN:1476-5594
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Hypoxia plays a critical role during the evolution of malignant cells and tumour microenvironment (TME).Tumour-derived exosomes contain informative microRNAs involved in the interaction of cancer and stromal cells, thus contributing to tissue remodelling of tumour microenvironment. This study aims to clarify how hypoxia affects tumour angiogenesis through exosomes shed from lung cancer cells. Lung cancer cells produce more exosomes under hypoxic conditions than do parental cells under normoxic conditions. miR-23a was significantly upregulated in exosomes from lung cancer under hypoxic conditions. Exosomal miR-23a directly suppressed its target prolyl hydroxylase 1 and 2 (PHD1 and 2), leading to the accumulation of hypoxia-inducible factor-1 α (HIF-1 α) in endothelial cells. Consequently, hypoxic lung cancer cells enhanced angiogenesis by exosomes derived from hypoxic cancer under both normoxic and hypoxic conditions. In addition, exosomal miR-23a also inhibits tight junction protein ZO-1, thereby increasing vascular permeability and cancer transendothelial migration. Inhibition of miR-23a by inhibitor administration decreased angiogenesis and tumour growth in a mouse model. Furthermore, elevated levels of circulating miR-23a are found in the sera of lung cancer patients, and miR-23a levels are positively correlated with proangiogenic activities. Taken together, our study reveals the clinical relevance and prognostic value of cancer-derived exosomal miR-23a under hypoxic conditions, and investigates a unique intercellular communication, mediated by cancer-derived exosomes, which modulates tumour vasculature.
[Mh] Termos MeSH primário: Permeabilidade Capilar/fisiologia
Exossomos/metabolismo
Neoplasias Pulmonares/metabolismo
MicroRNAs/metabolismo
Neovascularização Patológica/metabolismo
Prolil Hidroxilases/metabolismo
Proteína da Zônula de Oclusão-1/metabolismo
[Mh] Termos MeSH secundário: Animais
Hipóxia Celular/fisiologia
Linhagem Celular
Linhagem Celular Tumoral
Movimento Celular/fisiologia
Células Endoteliais da Veia Umbilical Humana
Seres Humanos
Hipóxia/metabolismo
Neoplasias Pulmonares/patologia
Masculino
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Nus
Proteínas de Junções Íntimas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (MicroRNAs); 0 (Tight Junction Proteins); 0 (Zonula Occludens-1 Protein); EC 1.14.11.- (Prolyl Hydroxylases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170925
[Lr] Data última revisão:
170925
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170425
[St] Status:MEDLINE
[do] DOI:10.1038/onc.2017.105


  8 / 121 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28419360
[Au] Autor:Zou Y; Donkervoort S; Salo AM; Foley AR; Barnes AM; Hu Y; Makareeva E; Leach ME; Mohassel P; Dastgir J; Deardorff MA; Cohn RD; DiNonno WO; Malfait F; Lek M; Leikin S; Marini JC; Myllyharju J; Bönnemann CG
[Ad] Endereço:Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
[Ti] Título:P4HA1 mutations cause a unique congenital disorder of connective tissue involving tendon, bone, muscle and the eye.
[So] Source:Hum Mol Genet;26(12):2207-2217, 2017 Jun 15.
[Is] ISSN:1460-2083
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Collagen prolyl 4-hydroxylases (C-P4Hs) play a central role in the formation and stabilization of the triple helical domain of collagens. P4HA1 encodes the catalytic α(I) subunit of the main C-P4H isoenzyme (C-P4H-I). We now report human bi-allelic P4HA1 mutations in a family with a congenital-onset disorder of connective tissue, manifesting as early-onset joint hypermobility, joint contractures, muscle weakness and bone dysplasia as well as high myopia, with evidence of clinical improvement of motor function over time in the surviving patient. Similar to P4ha1 null mice, which die prenatally, the muscle tissue from P1 and P2 was found to have reduced collagen IV immunoreactivity at the muscle basement membrane. Patients were compound heterozygous for frameshift and splice site mutations leading to reduced, but not absent, P4HA1 protein level and C-P4H activity in dermal fibroblasts compared to age-matched control samples. Differential scanning calorimetry revealed reduced thermal stability of collagen in patient-derived dermal fibroblasts versus age-matched control samples. Mutations affecting the family of C-P4Hs, and in particular C-P4H-I, should be considered in patients presenting with congenital connective tissue/myopathy overlap disorders with joint hypermobility, contractures, mild skeletal dysplasia and high myopia.
[Mh] Termos MeSH primário: Pró-Colágeno-Prolina Dioxigenase/genética
Pró-Colágeno-Prolina Dioxigenase/metabolismo
Prolil Hidroxilases/genética
[Mh] Termos MeSH secundário: Animais
Membrana Basal/metabolismo
Osso e Ossos/metabolismo
Criança
Colágeno Tipo IV/genética
Tecido Conjuntivo
Seres Humanos
Masculino
Camundongos
Camundongos Knockout
Músculos/metabolismo
Mutação
Osteocondrodisplasias/genética
Prolil Hidroxilases/metabolismo
Tendões/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Collagen Type IV); EC 1.14.11.- (Prolyl Hydroxylases); EC 1.14.11.2 (P4HA1 protein, human); EC 1.14.11.2 (Procollagen-Proline Dioxygenase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171012
[Lr] Data última revisão:
171012
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170419
[St] Status:MEDLINE
[do] DOI:10.1093/hmg/ddx110


  9 / 121 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28418093
[Au] Autor:Hulley PA; Bishop T; Vernet A; Schneider JE; Edwards JR; Athanasou NA; Knowles HJ
[Ad] Endereço:Nuffield Department of Orthopaedics Rheumatology & Musculoskeletal Sciences, University of Oxford, Oxford, UK.
[Ti] Título:Hypoxia-inducible factor 1-alpha does not regulate osteoclastogenesis but enhances bone resorption activity via prolyl-4-hydroxylase 2.
[So] Source:J Pathol;242(3):322-333, 2017 Jul.
[Is] ISSN:1096-9896
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Osteogenic-angiogenic coupling is promoted by the hypoxia-inducible factor 1-alpha (HIF-1α) transcription factor, provoking interest in HIF activation as a therapeutic strategy to improve osteoblast mineralization and treat pathological osteolysis. However, HIF also enhances the bone-resorbing activity of mature osteoclasts. It is therefore essential to determine the full effect(s) of HIF on both the formation and the bone-resorbing function of osteoclasts in order to understand how they might respond to such a strategy. Expression of HIF-1α mRNA and protein increased during osteoclast differentiation from CD14+ monocytic precursors, additionally inducing expression of the HIF-regulated glycolytic enzymes. However, HIF-1α siRNA only moderately affected osteoclast differentiation, accelerating fusion of precursor cells. HIF induction by inhibition of the regulatory prolyl-4-hydroxylase (PHD) enzymes reduced osteoclastogenesis, but was confirmed to enhance bone resorption by mature osteoclasts. Phd2 murine osteoclasts also exhibited enhanced bone resorption, associated with increased expression of resorption-associated Acp5, in comparison with wild-type cells from littermate controls. Phd3 bone marrow precursors displayed accelerated early fusion, mirroring results with HIF-1α siRNA. In vivo, Phd2 and Phd3 mice exhibited reduced trabecular bone mass, associated with reduced mineralization by Phd2 osteoblasts. These data indicate that HIF predominantly functions as a regulator of osteoclast-mediated bone resorption, with little effect on osteoclast differentiation. Inhibition of HIF might therefore represent an alternative strategy to treat diseases characterized by pathological levels of osteolysis. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
[Mh] Termos MeSH primário: Reabsorção Óssea/fisiopatologia
Subunidade alfa do Fator 1 Induzível por Hipóxia/fisiologia
Osteoclastos/fisiologia
Osteogênese/fisiologia
Prolil Hidroxilases/fisiologia
[Mh] Termos MeSH secundário: Animais
Osso Esponjoso/fisiologia
Adesão Celular/fisiologia
Diferenciação Celular/fisiologia
Feminino
Seres Humanos
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo
Prolina Dioxigenases do Fator Induzível por Hipóxia/deficiência
Leucócitos Mononucleares/patologia
Camundongos
RNA Mensageiro/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hypoxia-Inducible Factor 1, alpha Subunit); 0 (RNA, Messenger); EC 1.14.11.- (Prolyl Hydroxylases); EC 1.14.11.29 (Egln1 protein, mouse); EC 1.14.11.29 (Hypoxia-Inducible Factor-Proline Dioxygenases)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170828
[Lr] Data última revisão:
170828
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170419
[St] Status:MEDLINE
[do] DOI:10.1002/path.4906


  10 / 121 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28368464
[Au] Autor:Schaible B; Rodriguez J; Garcia A; von Kriegsheim A; McClean S; Hickey C; Keogh CE; Brown E; Schaffer K; Broquet A; Taylor CT
[Ad] Endereço:Conway Institute and.
[Ti] Título:Hypoxia Reduces the Pathogenicity of Pseudomonas aeruginosa by Decreasing the Expression of Multiple Virulence Factors.
[So] Source:J Infect Dis;215(9):1459-1467, 2017 May 01.
[Is] ISSN:1537-6613
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Our understanding of how the course of opportunistic bacterial infection is influenced by the microenvironment is limited. We demonstrate that the pathogenicity of Pseudomonas aeruginosa strains derived from acute clinical infections is higher than that of strains derived from chronic infections, where tissues are hypoxic. Exposure to hypoxia attenuated the pathogenicity of strains from acute (but not chronic) infections, implicating a role for hypoxia in regulating bacterial virulence. Mass spectrometric analysis of the secretome of P. aeruginosa derived from an acute infection revealed hypoxia-induced repression of multiple virulence factors independent of altered bacterial growth. Pseudomonas aeruginosa lacking the Pseudomonas prolyl-hydroxylase domain-containing protein, which has been implicated in bacterial oxygen sensing, displays reduced virulence factor expression. Furthermore, pharmacological hydroxylase inhibition reduces virulence factor expression and pathogenicity in a murine model of pneumonia. We hypothesize that hypoxia reduces P. aeruginosa virulence at least in part through the regulation of bacterial hydroxylases.
[Mh] Termos MeSH primário: Hipóxia Celular/fisiologia
Infecções por Pseudomonas/microbiologia
Pseudomonas aeruginosa/efeitos dos fármacos
Pseudomonas aeruginosa/patogenicidade
Fatores de Virulência/metabolismo
[Mh] Termos MeSH secundário: ADP Ribose Transferases/metabolismo
Doença Aguda
Animais
Proteínas de Bactérias/antagonistas & inibidores
Proteínas de Bactérias/metabolismo
Toxinas Bacterianas/metabolismo
Microambiente Celular/fisiologia
Doença Crônica
Exotoxinas/metabolismo
Camundongos
Oxigênio/farmacologia
Prolil Hidroxilases/metabolismo
Inibidores de Prolil-Hidrolase/metabolismo
Pseudomonas aeruginosa/metabolismo
Sideróforos/metabolismo
Fatores de Virulência/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Bacterial Toxins); 0 (Exotoxins); 0 (Prolyl-Hydroxylase Inhibitors); 0 (Siderophores); 0 (Virulence Factors); EC 1.14.11.- (Prolyl Hydroxylases); EC 2.4.2.- (ADP Ribose Transferases); EC 2.4.2.31 (toxA protein, Pseudomonas aeruginosa); S88TT14065 (Oxygen)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170816
[Lr] Data última revisão:
170816
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170404
[St] Status:MEDLINE
[do] DOI:10.1093/infdis/jix139



página 1 de 13 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