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[PMID]:29408309
[Au] Autor:Mohamed DI; Nabih ES; El-Waseef DAA; El-Kharashi OA; Abd El Samad AA
[Ad] Endereço:Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
[Ti] Título:The protective effect of pentoxifylline versus silymarin on the pancreas through increasing adenosine by CD39 in a rat model of liver cirrhosis: Pharmacological, biochemical and histological study.
[So] Source:Gene;651:9-22, 2018 Apr 20.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Impaired glucose homoeostasis due to insulin resistance and decrease sensitivity of pancreatic ß-cells is a feature of liver disease and results into hepatogenous diabetes. Decrease expression of CD39 was linked to inflammation and occurrence of diabetes. Therefore, we performed this study to explore the protective effect of pentoxifylline (PTX) and silymarin administration on the ß-cells of the pancreas in a rat model of thioacetamide induced liver cirrhosis. Biochemical, histological and immunohistochemistry studies of the liver and pancreas were performed and provided an evidence on the protective effect of PTX to pancreatic ß-cells compared to silymarin. Also, silymarin induced a significant improvement of liver cirrhosis compared to PTX. In conclusion, the potential protective effect of PTX against ß-cells deterioration could be attributed to increasing pancreatic CD39 expression and the subsequent increase of adenosine.
[Mh] Termos MeSH primário: Adenosina/metabolismo
Antígenos CD/metabolismo
Apirase/metabolismo
Cirrose Hepática Experimental/tratamento farmacológico
Pâncreas/efeitos dos fármacos
Pentoxifilina/uso terapêutico
Substâncias Protetoras/uso terapêutico
Silimarina/uso terapêutico
[Mh] Termos MeSH secundário: Amilases/sangue
Animais
Modelos Animais de Doenças
Células Secretoras de Insulina/efeitos dos fármacos
Fígado/patologia
Cirrose Hepática Experimental/metabolismo
Cirrose Hepática Experimental/patologia
Testes de Função Hepática
Masculino
Pâncreas/patologia
Ratos
Ratos Wistar
Fator de Crescimento Transformador beta1/metabolismo
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD); 0 (Protective Agents); 0 (Silymarin); 0 (Transforming Growth Factor beta1); EC 3.2.1.- (Amylases); EC 3.6.1.5 (Apyrase); EC 3.6.1.5 (CD39 antigen); K72T3FS567 (Adenosine); SD6QCT3TSU (Pentoxifylline)
[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:180207
[St] Status:MEDLINE


  2 / 1566 MEDLINE  
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[PMID]:28742222
[Au] Autor:Lanser AJ; Rezende RM; Rubino S; Lorello PJ; Donnelly DJ; Xu H; Lau LA; Dulla CG; Caldarone BJ; Robson SC; Weiner HL
[Ad] Endereço:Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
[Ti] Título:Disruption of the ATP/adenosine balance in CD39 mice is associated with handling-induced seizures.
[So] Source:Immunology;152(4):589-601, 2017 12.
[Is] ISSN:1365-2567
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Seizures are due to excessive, synchronous neuronal firing in the brain and are characteristic of epilepsy, the fourth most prevalent neurological disease. We report handling-induced and spontaneous seizures in mice deficient for CD39, a cell-surface ATPase highly expressed on microglial cells. CD39 mice with handling-induced seizures had normal input-output curves and paired-pulse ratio measured from hippocampal slices and lacked microgliosis, astrogliosis or overt cell loss in the hippocampus and cortex. As expected, however, the cerebrospinal fluid of CD39 mice contained increased levels of ATP and decreased levels of adenosine. To determine if immune activation was involved in seizure progression, we challenged mice with lipopolysaccharide (LPS) and measured the effect on microglia activation and seizure severity. Systemic LPS challenge resulted in increased cortical staining of Iba1/CD68 and gene array data from purified microglia predicted increased expression of interleukin-8, triggering receptor expressed on myeloid cells 1, p38, pattern recognition receptors, death receptor, nuclear factor-κB , complement, acute phase, and interleukin-6 signalling pathways in CD39 versus CD39 mice. However, LPS treatment did not affect handling-induced seizures. In addition, microglia-specific CD39 deletion in adult mice was not sufficient to cause seizures, suggesting instead that altered expression of CD39 during development or on non-microglial cells such as vascular endothelial cells may promote the seizure phenotype. In summary, we show a correlation between altered extracellular ATP/adenosine ratio and a previously unreported seizure phenotype in CD39 mice. This work provides groundwork for further elucidation of the underlying mechanisms of epilepsy.
[Mh] Termos MeSH primário: Trifosfato de Adenosina/imunologia
Adenosina/imunologia
Apirase/deficiência
Córtex Cerebral/imunologia
Hipocampo/imunologia
Convulsões/imunologia
[Mh] Termos MeSH secundário: Adenosina/genética
Trifosfato de Adenosina/genética
Animais
Antígenos CD/imunologia
Apirase/imunologia
Proteínas de Ligação ao Cálcio/genética
Proteínas de Ligação ao Cálcio/imunologia
Córtex Cerebral/patologia
Hipocampo/patologia
Lipopolissacarídeos/toxicidade
Camundongos
Camundongos Knockout
Proteínas dos Microfilamentos/genética
Proteínas dos Microfilamentos/imunologia
Convulsões/genética
Convulsões/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aif1 protein, mouse); 0 (Antigens, CD); 0 (Calcium-Binding Proteins); 0 (Lipopolysaccharides); 0 (Microfilament Proteins); 8L70Q75FXE (Adenosine Triphosphate); EC 3.6.1.5 (Apyrase); EC 3.6.1.5 (CD39 antigen); K72T3FS567 (Adenosine)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170726
[St] Status:MEDLINE
[do] DOI:10.1111/imm.12798


  3 / 1566 MEDLINE  
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[PMID]:28464260
[Au] Autor:Martínez-Ramírez AS; Díaz-Muñoz M; Battastini AM; Campos-Contreras A; Olvera A; Bergamin L; Glaser T; Jacintho Moritz CE; Ulrich H; Vázquez-Cuevas FG
[Ad] Endereço:Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Boulevard Juriquilla 3001, Juriquilla Querétaro, CP 76230, Querétaro, México.
[Ti] Título:Cellular Migration Ability Is Modulated by Extracellular Purines in Ovarian Carcinoma SKOV-3 Cells.
[So] Source:J Cell Biochem;118(12):4468-4478, 2017 Dec.
[Is] ISSN:1097-4644
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Extracellular nucleotides and nucleosides have emerged as important elements regulating tissue homeostasis. Acting through specific receptors, have the ability to control gene expression patterns to direct cellular fate. We observed that SKOV-3 cells express the ectonucleotidases: ectonucleotide pyrophosphatase 1 (ENPP1), ecto-5'-nucleotidase (NT5E), and liver alkaline phosphatase (ALPL). Strikingly, in pulse and chase experiments supplemented with ATP, SKOV-3 cells exhibited low catabolic efficiency in the conversion of ADP into AMP, but they were efficient in converting AMP into adenosine. Since these cells release ATP, we proposed that the conversion of ADP into AMP is a regulatory node associated with the migratory ability and the mesenchymal characteristics shown by SKOV-3 cells under basal conditions. The landscape of gene expression profiles of SKOV-3 cell cultures treated with apyrase or adenosine demonstrated similarities (e.g., decrease FGF16 transcript) and differences (e.g., the negative regulation of Wnt 2, and 10B by adenosine). Thus, in SKOV-3 we analyzed the migratory ability and the expression of epithelium to mesenchymal transition (EMT) markers in response to apyrase. Apyrase-treatment favored the epithelial-like phenotype, as revealed by the re-location of E-cadherin to the cell to cell junctions. Pharmacological approaches strongly suggested that the effect of Apyrase involved the accumulation of extracellular adenosine; this notion was strengthened when the incubation of the SKOV-3 cell with α,ß-methylene ADP (CD73 inhibitor) or adenosine deaminase was sufficient to abolish the effect of apyrase on cell migration. Overall, adenosine signaling is a fine tune mechanism in the control of cell phenotype in cancer. J. Cell. Biochem. 118: 4468-4478, 2017. © 2017 Wiley Periodicals, Inc.
[Mh] Termos MeSH primário: Movimento Celular/efeitos dos fármacos
Neoplasias Ovarianas/metabolismo
Purinas/farmacologia
[Mh] Termos MeSH secundário: Apirase/metabolismo
Linhagem Celular Tumoral
Transição Epitelial-Mesenquimal/efeitos dos fármacos
Feminino
Seres Humanos
Proteínas de Neoplasias/metabolismo
Purinas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Neoplasm Proteins); 0 (Purines); EC 3.6.1.5 (Apyrase)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180102
[Lr] Data última revisão:
180102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1002/jcb.26104


  4 / 1566 MEDLINE  
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[PMID]:29176764
[Au] Autor:Gregersen I; Sandanger Ø; Askevold ET; Sagen EL; Yang K; Holm S; Pedersen TM; Skjelland M; Krohg-Sørensen K; Hansen TV; Dahl TB; Otterdal K; Espevik T; Aukrust P; Yndestad A; Halvorsen B
[Ad] Endereço:Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet,Oslo, Norway.
[Ti] Título:Interleukin 27 is increased in carotid atherosclerosis and promotes NLRP3 inflammasome activation.
[So] Source:PLoS One;12(11):e0188387, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:AIM: Interleukin-27 (IL-27) is involved in different inflammatory diseases; however, its role in atherosclerosis is unclear. In this study we investigated the expression of IL-27 and its receptor in patients with carotid atherosclerosis and if IL-27 could modulate the inflammatory effects of the NLRP3 inflammasome in vitro. METHODS: Plasma IL-27 was measured by enzyme immunoassay in patients with carotid stenosis (n = 140) and in healthy controls (n = 19). Expression of IL-27 and IL-27R was analyzed by quantitative PCR and immunohistochemistry in plaques from patients and in non-atherosclerotic vessels. THP-1 monocytes, primary monocytes and peripheral blood mononuclear cells (PBMCs) were used to study effects of IL-27 in vitro. RESULTS: Our main findings were: (i) Plasma levels of IL-27 were significantly elevated in patients with carotid atherosclerotic disease compared to healthy controls. (ii) Gene expression of IL-27 and IL-27R was significantly elevated in plaques compared to control vessels, and co-localized to macrophages. (iii) In vitro, IL-27 increased NLRP3 inflammasome activation in monocytes with enhanced release of IL-1 ß. CONCLUSIONS: We demonstrate increased levels of IL-27 and IL-27R in patients with carotid atherosclerosis. Our in vitro findings suggest an inflammatory role for IL-27, which can possibly be linked to atherosclerotic disease development.
[Mh] Termos MeSH primário: Doenças das Artérias Carótidas/metabolismo
Inflamassomos/metabolismo
Interleucina-27/metabolismo
Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo
[Mh] Termos MeSH secundário: Idoso
Antígenos CD/metabolismo
Apirase/metabolismo
Doenças das Artérias Carótidas/sangue
Doenças das Artérias Carótidas/genética
Doenças das Artérias Carótidas/patologia
Feminino
Regulação da Expressão Gênica
Seres Humanos
Interleucina-1beta/metabolismo
Interleucina-27/sangue
Interleucina-27/genética
Interleucinas/metabolismo
Lipopolissacarídeos
Macrófagos/metabolismo
Masculino
Antígenos de Histocompatibilidade Menor/metabolismo
Monócitos/metabolismo
Placa Aterosclerótica/metabolismo
Placa Aterosclerótica/patologia
Receptores de Citocinas/genética
Receptores de Citocinas/metabolismo
Fatores de Transcrição STAT/metabolismo
Transdução de Sinais
Fator de Necrose Tumoral alfa/metabolismo
Regulação para Cima/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD); 0 (EBI3 protein, human); 0 (Inflammasomes); 0 (Interleukin-1beta); 0 (Interleukin-27); 0 (Interleukins); 0 (Lipopolysaccharides); 0 (Minor Histocompatibility Antigens); 0 (NLR Family, Pyrin Domain-Containing 3 Protein); 0 (Receptors, Cytokine); 0 (STAT Transcription Factors); 0 (Tumor Necrosis Factor-alpha); EC 3.6.1.5 (Apyrase); EC 3.6.1.5 (CD39 antigen)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171219
[Lr] Data última revisão:
171219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0188387


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[PMID]:28980000
[Au] Autor:Hu P; Hunt NH; Arfuso F; Shaw LC; Uddin MN; Zhu M; Devasahayam R; Adamson SJ; Benson VL; Chan-Ling T; Grant MB
[Ad] Endereço:Department of Anatomy, Bosch Institute, University of Sydney, New South Wales, Australia.
[Ti] Título:Increased Indoleamine 2,3-Dioxygenase and Quinolinic Acid Expression in Microglia and Müller Cells of Diabetic Human and Rodent Retina.
[So] Source:Invest Ophthalmol Vis Sci;58(12):5043-5055, 2017 Oct 01.
[Is] ISSN:1552-5783
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Purpose: We investigated the relationship between inflammation, neuronal loss, and expression of indoleamine 2, 3-dioxygenase (IDO) and quinolinic acid (QUIN) in the retina of subjects with type 1 diabetes (T1D) and type 2 diabetes (T2D) and in the retina of rats with T1D. Methods: Retinas from T1D (n = 7), T2D (n = 13), and 20 age-matched nondiabetic human donors and from T1D (n = 3) and control rats (n = 3) were examined using immunohistochemistry for IDO, QUIN, cluster of differentiation 39 (CD39), ionized calcium-binding adaptor molecule (Iba-1, for macrophages and microglia), Vimentin (VIM; for Müller cells), neuronal nuclei (NeuN; for neurons), and UEA1 lectin (for blood vessels). Results: Based on morphologic criteria, CD39+/ionized calcium binding adaptor molecule 1(Iba-1+) resident microglia and CD39-/Iba-1+ bone marrow-derived macrophages were present at higher density in T1D (13% increase) and T2D (26% increase) human retinas when compared with controls. The density and brightness of IDO+ microglia were increased in both T1D and T2D human retinas. The intensity of QUIN+ expression on CD39+ microglia and VIM+ Müller cells was greatly increased in both human T1D and T2D retinas. T1D retinas showed a 63% loss of NeuN+ neurons and T2D retinas lost approximately 43% when compared with nondiabetic human retinas. Few QUIN+ microglia-like cells were seen in nondiabetic retinas, but the numbers increased 18-fold in T1D and 7-fold in T2D in the central retina. In T1D rat retinas, the density of IDO+ microglia increased 2.8-fold and brightness increased 2.1-fold when compared with controls. Conclusions: Our findings suggest that IDO and QUIN expression in the retinas of diabetic rats and humans could contribute to the neuronal degeneration that is characteristic of diabetic retinopathy.
[Mh] Termos MeSH primário: Biomarcadores/metabolismo
Retinopatia Diabética/metabolismo
Células Ependimogliais/metabolismo
Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo
Microglia/metabolismo
Ácido Quinolínico/metabolismo
Retina/metabolismo
[Mh] Termos MeSH secundário: Idoso
Animais
Antígenos CD/metabolismo
Antígenos Nucleares/metabolismo
Apirase/metabolismo
Proteínas de Ligação ao Cálcio/metabolismo
Proteínas de Ligação a DNA/metabolismo
Diabetes Mellitus Experimental/metabolismo
Diabetes Mellitus Tipo 1/metabolismo
Diabetes Mellitus Tipo 2/metabolismo
Retinopatia Diabética/patologia
Células Ependimogliais/patologia
Feminino
Técnica Indireta de Fluorescência para Anticorpo
Seres Humanos
Masculino
Proteínas dos Microfilamentos/metabolismo
Microglia/patologia
Microscopia Confocal
Meia-Idade
Proteínas do Tecido Nervoso/metabolismo
Ratos
Ratos Sprague-Dawley
Retina/patologia
Vimentina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AIF1 protein, human); 0 (Aif1 protein, rat); 0 (Antigens, CD); 0 (Antigens, Nuclear); 0 (Biomarkers); 0 (Calcium-Binding Proteins); 0 (DNA-Binding Proteins); 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase); 0 (Microfilament Proteins); 0 (Nerve Tissue Proteins); 0 (NeuN protein, rat); 0 (Vimentin); 0 (neuronal nuclear antigen NeuN, human); EC 3.6.1.5 (Apyrase); EC 3.6.1.5 (CD39 antigen); F6F0HK1URN (Quinolinic Acid)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171020
[Lr] Data última revisão:
171020
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171006
[St] Status:MEDLINE
[do] DOI:10.1167/iovs.17-21654


  6 / 1566 MEDLINE  
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[PMID]:28800362
[Au] Autor:Jiang P; Xing F; Guo B; Yang J; Li Z; Wei W; Hu F; Lee I; Zhang X; Pan L; Xu J
[Ad] Endereço:The Key Laboratory of Weak-Light Nonlinear Photonics, Ministry of Education, TEDA Institute of Applied Physics and School of Physics, Nankai University, Tianjin, China.
[Ti] Título:Nucleotide transmitters ATP and ADP mediate intercellular calcium wave communication via P2Y12/13 receptors among BV-2 microglia.
[So] Source:PLoS One;12(8):e0183114, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Nerve injury is accompanied by a liberation of diverse nucleotides, some of which act as 'find/eat-me' signals in mediating neuron-glial interplay. Intercellular Ca2+ wave (ICW) communication is the main approach by which glial cells interact and coordinate with each other to execute immune defense. However, the detailed mechanisms on how these nucleotides participate in ICW communication remain largely unclear. In the present work, we employed a mechanical stimulus to an individual BV-2 microglia to simulate localized injury. Remarkable ICW propagation was observed no matter whether calcium was in the environment or not. Apyrase (ATP/ADP-hydrolyzing enzyme), suramin (broad-spectrum P2 receptor antagonist), 2-APB (IP3 receptor blocker) and thapsigargin (endoplasmic reticulum calcium pump inhibitor) potently inhibited these ICWs, respectively, indicating the dependence of nucleotide signals and P2Y receptors. Then, we detected the involvement of five naturally occurring nucleotides (ATP, ADP, UTP, UDP and UDP-glucose) by desensitizing receptors. Results showed that desensitization with ATP and ADP could block ICW propagation in a dose-dependent manner, whereas other nucleotides had little effect. Meanwhile, the expression of P2Y receptors in BV-2 microglia was identified and their contributions were analyzed, from which we suggested P2Y12/13 receptors activation mostly contributed to ICWs. Besides, we estimated that extracellular ATP and ADP concentration sensed by BV-2 microglia was about 0.3 µM during ICWs by analyzing calcium dynamic characteristics. Taken together, these results demonstrated that the nucleotides ATP and ADP were predominant signal transmitters in mechanical stimulation-induced ICW communication through acting on P2Y12/13 receptors in BV-2 microglia.
[Mh] Termos MeSH primário: Difosfato de Adenosina/metabolismo
Trifosfato de Adenosina/metabolismo
Cálcio/metabolismo
Microglia/metabolismo
Receptores Purinérgicos P2Y12/metabolismo
Receptores Purinérgicos P2/metabolismo
[Mh] Termos MeSH secundário: Animais
Apirase/farmacologia
Fenômenos Biomecânicos
Compostos de Boro/farmacologia
Sinalização do Cálcio/efeitos dos fármacos
Comunicação Celular/efeitos dos fármacos
Linhagem Celular Transformada
Expressão Gênica
Fosfatos de Inositol/farmacologia
Mecanotransdução Celular/efeitos dos fármacos
Camundongos
Microglia/citologia
Microglia/efeitos dos fármacos
Imagem Molecular
Receptores Purinérgicos P2/genética
Receptores Purinérgicos P2Y12/genética
Suramina/farmacologia
Tapsigargina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (2-aminoethyl diphenylborinate); 0 (Boron Compounds); 0 (Inositol Phosphates); 0 (P2ry12 protein, mouse); 0 (P2ry13 protein, mouse); 0 (Receptors, Purinergic P2); 0 (Receptors, Purinergic P2Y12); 2831-74-5 (inositol 3-phosphate); 6032D45BEM (Suramin); 61D2G4IYVH (Adenosine Diphosphate); 67526-95-8 (Thapsigargin); 8L70Q75FXE (Adenosine Triphosphate); EC 3.6.1.5 (Apyrase); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171006
[Lr] Data última revisão:
171006
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170812
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0183114


  7 / 1566 MEDLINE  
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[PMID]:28679740
[Au] Autor:Cho MS; Noh K; Haemmerle M; Li D; Park H; Hu Q; Hisamatsu T; Mitamura T; Mak SLC; Kunapuli S; Ma Q; Sood AK; Afshar-Kharghan V
[Ad] Endereço:Department of Benign Hematology, University of Texas MD Anderson Cancer Center, Houston, TX.
[Ti] Título:Role of ADP receptors on platelets in the growth of ovarian cancer.
[So] Source:Blood;130(10):1235-1242, 2017 Sep 07.
[Is] ISSN:1528-0020
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We investigated the effect of platelets on ovarian cancer and the role of adenosine diphosphate (ADP) receptors (P2Y12 and P2Y1) on platelets in the growth of primary ovarian cancer tumors. We showed that in murine models of ovarian cancer, a P2Y12 inhibitor (ticagrelor) reduced tumor growth by 60% compared with aspirin and by 75% compared with placebo. In P2Y12 mice, the growth of syngeneic ovarian cancer tumors was reduced by >85% compared with wild-type (WT) mice. In contrast, there was no difference in tumor growth between P2Y1 and WT mice. Reconstitution of hematopoiesis in irradiated P2Y12 mice by hematopoietic progenitor cells from WT mice (WT→P2Y12 ) restored tumor growth in P2Y12 mice. Finally, knockdown of ecto-apyrase (CD39) on ovarian cancer cells increased tumor growth in tumor-bearing mice. Although in the absence of platelets, ADP, the P2Y12 inhibitor, recombinant apyrase, or knockdown of CD39 did not affect cancer cell proliferation, in the presence of platelets, the P2Y12 inhibitor and recombinant apyrase reduced and knockdown of CD39 increased platelet-enhanced cancer cell proliferation. These results suggest that P2Y12 on platelets and ADP concentration at the interface between cancer cells and platelets affect the growth of primary ovarian cancer tumors in mice. If additional studies in mice and in pilot human trials confirm our results, inhibition of P2Y12 might be a new therapeutic option that can be used in adjuvant to the traditional surgery and chemotherapy in patients with ovarian cancer.
[Mh] Termos MeSH primário: Plaquetas/metabolismo
Neoplasias Ovarianas/sangue
Neoplasias Ovarianas/patologia
Receptores Purinérgicos P2Y12/metabolismo
Receptores Purinérgicos P2Y1/metabolismo
[Mh] Termos MeSH secundário: Adenosina/análogos & derivados
Adenosina/farmacologia
Transferência Adotiva
Animais
Antígenos CD/metabolismo
Apoptose/efeitos dos fármacos
Apirase/metabolismo
Plaquetas/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Feminino
Técnicas de Silenciamento de Genes
Hematopoese/efeitos dos fármacos
Seres Humanos
Camundongos Endogâmicos C57BL
Neoplasias Ovarianas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD); 0 (Receptors, Purinergic P2Y1); 0 (Receptors, Purinergic P2Y12); EC 3.6.1.5 (Apyrase); EC 3.6.1.5 (CD39 antigen); GLH0314RVC (Ticagrelor); K72T3FS567 (Adenosine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171008
[Lr] Data última revisão:
171008
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170707
[St] Status:MEDLINE
[do] DOI:10.1182/blood-2017-02-769893


  8 / 1566 MEDLINE  
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[PMID]:28543850
[Au] Autor:Summers EL; Cumming MH; Oulavallickal T; Roberts NJ; Arcus VL
[Ad] Endereço:School of Science, University of Waikato, Private Bag 3105, Hamilton, 3240, New Zealand.
[Ti] Título:Structures and kinetics for plant nucleoside triphosphate diphosphohydrolases support a domain motion catalytic mechanism.
[So] Source:Protein Sci;26(8):1627-1638, 2017 Aug.
[Is] ISSN:1469-896X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Extracellular nucleoside triphosphate diphosphohydrolases (NTPDases) are enzymes that hydrolyze extracellular nucleotides to the respective monophosphate nucleotides. In the past 20 years, NTPDases belonging to mammalian, parasitic and prokaryotic domains of life have been discovered, cloned and characterized. We reveal the first structures of NTPDases from the legume plant species Trifolium repens (7WC) and Vigna unguiculata subsp. cylindrica (DbLNP). Four crystal structures of 7WC and DbLNP were determined at resolutions between 1.9 and 2.6 Å. For 7WC, structures were determined for an -apo form (1.89 Å) and with the product AMP (2.15 Å) and adenine and phosphate (1.76 Å) bound. For DbLNP, a structure was solved with phosphate and manganese bound (2.60 Å). Thorough kinetic data and analysis is presented. The structure of 7WC and DbLNP reveals that these NTPDases can adopt two conformations depending on the molecule and co-factor bound in the active site. A central hinge region creates a "butterfly-like" motion of the domains that reduces the width of the inter-domain active site cleft upon molecule binding. This phenomenon has been previously described in Rattus norvegicus and Legionella pneumophila NTPDaseI and Toxoplasma gondii NTPDaseIII suggesting a common catalytic mechanism across the domains of life.
[Mh] Termos MeSH primário: Monofosfato de Adenosina/química
Trifosfato de Adenosina/química
Apirase/química
Proteínas de Plantas/química
Trifolium/química
Vigna/química
[Mh] Termos MeSH secundário: Monofosfato de Adenosina/metabolismo
Trifosfato de Adenosina/metabolismo
Sequência de Aminoácidos
Animais
Apirase/genética
Apirase/metabolismo
Domínio Catalítico
Clonagem Molecular
Cristalografia por Raios X
Escherichia coli/genética
Escherichia coli/metabolismo
Expressão Gênica
Isoenzimas/química
Isoenzimas/genética
Isoenzimas/metabolismo
Cinética
Legionella pneumophila/química
Legionella pneumophila/enzimologia
Manganês/química
Manganês/metabolismo
Modelos Moleculares
Fosfatos/química
Fosfatos/metabolismo
Proteínas de Plantas/genética
Proteínas de Plantas/metabolismo
Ligação Proteica
Conformação Proteica em alfa-Hélice
Conformação Proteica em Folha beta
Domínios e Motivos de Interação entre Proteínas
Ratos
Proteínas Recombinantes/química
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Alinhamento de Sequência
Homologia de Sequência de Aminoácidos
Especificidade por Substrato
Toxoplasma/química
Toxoplasma/enzimologia
Trifolium/enzimologia
Vigna/enzimologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Isoenzymes); 0 (Phosphates); 0 (Plant Proteins); 0 (Recombinant Proteins); 415SHH325A (Adenosine Monophosphate); 42Z2K6ZL8P (Manganese); 8L70Q75FXE (Adenosine Triphosphate); EC 3.6.1.5 (Apyrase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170824
[Lr] Data última revisão:
170824
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170526
[St] Status:MEDLINE
[do] DOI:10.1002/pro.3199


  9 / 1566 MEDLINE  
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[PMID]:28414024
[Au] Autor:Zhang H; Chan LL; Rice W; Kassam N; Longhi MS; Zhao H; Robson SC; Gao W; Wu Y
[Ad] Endereço:Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States.
[Ti] Título:Novel high-throughput cell-based hybridoma screening methodology using the Celigo Image Cytometer.
[So] Source:J Immunol Methods;447:23-30, 2017 Aug.
[Is] ISSN:1872-7905
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Hybridoma screening is a critical step for antibody discovery, which necessitates prompt identification of potential clones from hundreds to thousands of hybridoma cultures against the desired immunogen. Technical issues associated with ELISA- and flow cytometry-based screening limit accuracy and diminish high-throughput capability, increasing time and cost. Conventional ELISA screening with coated antigen is also impractical for difficult-to-express hydrophobic membrane antigens or multi-chain protein complexes. Here, we demonstrate novel high-throughput screening methodology employing the Celigo Image Cytometer, which avoids nonspecific signals by contrasting antibody binding signals directly on living cells, with and without recombinant antigen expression. The image cytometry-based high-throughput screening method was optimized by detecting the binding of hybridoma supernatants to the recombinant antigen CD39 expressed on Chinese hamster ovary (CHO) cells. Next, the sensitivity of the image cytometer was demonstrated by serial dilution of purified CD39 antibody. Celigo was used to measure antibody affinities of commercial and in-house antibodies to membrane-bound CD39. This cell-based screening procedure can be completely accomplished within one day, significantly improving throughput and efficiency of hybridoma screening. Furthermore, measuring direct antibody binding to living cells eliminated both false positive and false negative hits. The image cytometry method was highly sensitive and versatile, and could detect positive antibody in supernatants at concentrations as low as ~5ng/mL, with concurrent K binding affinity coefficient determination. We propose that this screening method will greatly facilitate antibody discovery and screening technologies.
[Mh] Termos MeSH primário: Anticorpos Monoclonais/isolamento & purificação
Ensaios de Triagem em Larga Escala/instrumentação
Ensaios de Triagem em Larga Escala/métodos
Citometria por Imagem/métodos
[Mh] Termos MeSH secundário: Animais
Anticorpos Monoclonais/imunologia
Afinidade de Anticorpos
Antígenos CD/genética
Antígenos CD/imunologia
Apirase/genética
Apirase/imunologia
Células CHO
Cricetulus
Ensaio de Imunoadsorção Enzimática/métodos
Hibridomas/imunologia
Sensibilidade e Especificidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Antigens, CD); EC 3.6.1.5 (Apyrase); EC 3.6.1.5 (CD39 antigen)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170915
[Lr] Data última revisão:
170915
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170418
[St] Status:MEDLINE


  10 / 1566 MEDLINE  
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[PMID]:28377485
[Au] Autor:Baek AE; Sutton NR; Petrovic-Djergovic D; Liao H; Ray JJ; Park J; Kanthi Y; Pinsky DJ
[Ad] Endereço:From Department of Molecular and Integrative Physiology (A.E.B., D.J.P.) and Department of Internal Medicine (N.R.S., D.P.-D, H.L., J.R., Y.K., D.J.P.), Division of Cardiovascular Medicine University of Michigan Medical Center, Ann Arbor; and Section of Cardiology, VA Ann Arbor Healthcare System, MI
[Ti] Título:Ischemic Cerebroprotection Conferred by Myeloid Lineage-Restricted or Global CD39 Transgene Expression.
[So] Source:Circulation;135(24):2389-2402, 2017 Jun 13.
[Is] ISSN:1524-4539
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Cerebral tissue damage after an ischemic event can be exacerbated by inflammation and thrombosis. Elevated extracellular ATP and ADP levels are associated with cellular injury, inflammation, and thrombosis. Ectonucleoside triphosphate diphosphohydrolase-1 (CD39), an enzyme expressed on the plasmalemma of leukocytes and endothelial cells, suppresses platelet activation and leukocyte infiltration by phosphohydrolyzing ATP/ADP. To investigate the effects of increased CD39 in an in vivo cerebral ischemia model, we developed a transgenic mouse expressing human CD39 (hCD39). METHODS: A floxed-stop sequence was inserted between the promoter and the hCD39 transcriptional start site, generating a mouse in which the expression of hCD39 can be controlled tissue-specifically using Cre recombinase mice. We generated mice that express hCD39 globally or in myeloid-lineage cells only. Cerebral ischemia was induced by middle cerebral artery occlusion. Infarct volumes were quantified by MRI after 48 hours. RESULTS: Both global and transgenic hCD39- and myeloid lineage CD39-overexpressing mice (transgenic, n=9; myeloid lineage, n=6) demonstrated significantly smaller cerebral infarct volumes compared with wild-type mice. Leukocytes from ischemic and contralateral hemispheres were analyzed by flow cytometry. Although contralateral hemispheres had equal numbers of macrophages and neutrophils, ischemic hemispheres from transgenic mice had less infiltration (n=4). Transgenic mice showed less neurological deficit compared with wild-type mice (n=6). CONCLUSIONS: This is the first report of transgenic overexpression of CD39 in mice imparting a protective phenotype after stroke, with reduced leukocyte infiltration, smaller infarct volumes, and decreased neurological deficit. CD39 overexpression, either globally or in myeloid lineage cells, quenches postischemic leukosequestration and reduces stroke-induced neurological injury.
[Mh] Termos MeSH primário: Antígenos CD/biossíntese
Antígenos CD/genética
Apirase/biossíntese
Apirase/genética
Isquemia Encefálica/genética
Isquemia Encefálica/metabolismo
Linhagem da Célula/fisiologia
Transgenes/fisiologia
[Mh] Termos MeSH secundário: Animais
Isquemia Encefálica/prevenção & controle
Expressão Gênica
Seres Humanos
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Células Mieloides/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD); EC 3.6.1.5 (Apyrase); EC 3.6.1.5 (CD39 antigen)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171018
[Lr] Data última revisão:
171018
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170406
[St] Status:MEDLINE
[do] DOI:10.1161/CIRCULATIONAHA.116.023301



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