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[PMID]:28511668
[Au] Autor:Muruganandam G; Raasakka A; Myllykoski M; Kursula I; Kursula P
[Ad] Endereço:Centre for Structural Systems Biology - Helmholtz Centre for Infection Research, German Electron Synchrotron (DESY), Hamburg, Germany.
[Ti] Título:Structural similarities and functional differences clarify evolutionary relationships between tRNA healing enzymes and the myelin enzyme CNPase.
[So] Source:BMC Biochem;18(1):7, 2017 May 16.
[Is] ISSN:1471-2091
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Eukaryotic tRNA splicing is an essential process in the transformation of a primary tRNA transcript into a mature functional tRNA molecule. 5'-phosphate ligation involves two steps: a healing reaction catalyzed by polynucleotide kinase (PNK) in association with cyclic phosphodiesterase (CPDase), and a sealing reaction catalyzed by an RNA ligase. The enzymes that catalyze tRNA healing in yeast and higher eukaryotes are homologous to the members of the 2H phosphoesterase superfamily, in particular to the vertebrate myelin enzyme 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase). RESULTS: We employed different biophysical and biochemical methods to elucidate the overall structural and functional features of the tRNA healing enzymes yeast Trl1 PNK/CPDase and lancelet PNK/CPDase and compared them with vertebrate CNPase. The yeast and the lancelet enzymes have cyclic phosphodiesterase and polynucleotide kinase activity, while vertebrate CNPase lacks PNK activity. In addition, we also show that the healing enzymes are structurally similar to the vertebrate CNPase by applying synchrotron radiation circular dichroism spectroscopy and small-angle X-ray scattering. CONCLUSIONS: We provide a structural analysis of the tRNA healing enzyme PNK and CPDase domains together. Our results support evolution of vertebrate CNPase from tRNA healing enzymes with a loss of function at its N-terminal PNK-like domain.
[Mh] Termos MeSH primário: 2´,3´-Nucleotídeo Cíclico Fosfodiesterases/química
Evolução Molecular
[Mh] Termos MeSH secundário: 2',3'-Nucleotídeo Cíclico Fosfodiesterases/metabolismo
2',3'-Nucleotídeo Cíclico Fosfodiesterases/fisiologia
Animais
Dicroísmo Circular
Células Eucarióticas/enzimologia
Anfioxos
Camundongos
Bainha de Mielina/enzimologia
Polinucleotídeo 5'-Hidroxiquinase/química
Polinucleotídeo 5'-Hidroxiquinase/metabolismo
Processamento de RNA
RNA de Transferência/genética
Saccharomyces cerevisiae
Espalhamento a Baixo Ângulo
Difração de Raios X
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
9014-25-9 (RNA, Transfer); EC 2.7.1.78 (Polynucleotide 5'-Hydroxyl-Kinase); EC 3.1.4.- (2',3'-Cyclic-Nucleotide Phosphodiesterases)
[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:170518
[St] Status:MEDLINE
[do] DOI:10.1186/s12858-017-0084-2


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[PMID]:28445714
[Au] Autor:Stivers NS; Pelisch N; Orem BC; Williams J; Nally JM; Stirling DP
[Ad] Endereço:Kentucky Spinal Cord Injury Research Center and Departments of Neurological Surgery, Microbiology and Immunology, Anatomical Sciences and Neurobiology, University of Louisville, Louisville, KY, USA.
[Ti] Título:The toll-like receptor 2 agonist Pam3CSK4 is neuroprotective after spinal cord injury.
[So] Source:Exp Neurol;294:1-11, 2017 Aug.
[Is] ISSN:1090-2430
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Microglia/macrophage activation and recruitment following spinal cord injury (SCI) is associated with both detrimental and reparative functions. Stimulation of the innate immune receptor Toll-like receptor-2 (TLR2) has shown to be beneficial following SCI, and it increases axonal regeneration following optic nerve crush. However, the mechanism(s) remain unclear. As microglia express high levels of TLR2, we hypothesized that modulating the microglial response to injury using a specific TLR2 agonist, Pam3CSK4, would prevent secondary-mediated white matter degeneration following SCI. To test this hypothesis, we documented acute changes in microglia, axons, and oligodendroglia over time using two-photon excitation and an ex vivo laser-induced SCI (LiSCI) model. We utilized double transgenic mice that express GFP in either microglia or oligodendroglia, and YFP in axons, and we applied the lipophilic fluorescent dye (Nile Red) to visualize myelin. We found that treatment with Pam3CSK4 initiated one hour after injury induced a significant increase in the extent and timing of the microglial response to injury compared to vehicle controls. This enhanced response was observed 2 to 4h following SCI and was most prominent in areas closer to the ablation site. In addition, Pam3CSK4 treatment significantly reduced axonal dieback rostral and caudal to the ablation at 6h post-SCI. This protective effect of Pam3CSK4 was also mirrored when assessing secondary bystander axonal damage (i.e., axons spared by the primary injury that then succumb to secondary degeneration), and when assessing the survival of oligodendroglia. Following these imaging experiments, custom microarray analysis of the ex vivo spinal cord preparations revealed that Pam3CSK4-treatment induced an alternative (mixed M1:M2) microglial activation profile. In summary, our data suggest that by providing a second "sterile" activation signal to microglia through TLR2/TLR1 signaling, the microglial response to injury can be modulated in situ and is highly neuroprotective.
[Mh] Termos MeSH primário: Regulação da Expressão Gênica/efeitos dos fármacos
Lipopeptídeos/farmacologia
Lipopeptídeos/uso terapêutico
Degeneração Neural/tratamento farmacológico
Traumatismos da Medula Espinal/tratamento farmacológico
[Mh] Termos MeSH secundário: 2',3'-Nucleotídeo Cíclico Fosfodiesterases/genética
2',3'-Nucleotídeo Cíclico Fosfodiesterases/metabolismo
Animais
Axônios/efeitos dos fármacos
Axônios/patologia
Receptor 1 de Quimiocina CX3C
Citocinas/metabolismo
Modelos Animais de Doenças
Regulação da Expressão Gênica/genética
Inflamação/tratamento farmacológico
Inflamação/etiologia
Inflamação/metabolismo
Terapia a Laser/efeitos adversos
Proteínas Luminescentes/genética
Proteínas Luminescentes/metabolismo
Ativação de Macrófagos
Glicoproteínas de Membrana/metabolismo
Camundongos
Camundongos Transgênicos
Microglia/efeitos dos fármacos
Degeneração Neural/etiologia
Fármacos Neuroprotetores/farmacologia
Fármacos Neuroprotetores/uso terapêutico
Receptores de Superfície Celular/metabolismo
Receptores de Quimiocinas/genética
Receptores de Quimiocinas/metabolismo
Traumatismos da Medula Espinal/complicações
Traumatismos da Medula Espinal/etiologia
Traumatismos da Medula Espinal/patologia
Antígenos Thy-1/genética
Antígenos Thy-1/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CX3C Chemokine Receptor 1); 0 (Cx3cr1 protein, mouse); 0 (Cytokines); 0 (Lipopeptides); 0 (Luminescent Proteins); 0 (MRC1 protein, mouse); 0 (Membrane Glycoproteins); 0 (Neuroprotective Agents); 0 (Pam(3)CSK(4) peptide); 0 (Receptors, Cell Surface); 0 (Receptors, Chemokine); 0 (Thy-1 Antigens); EC 3.1.4.- (2',3'-Cyclic-Nucleotide Phosphodiesterases)
[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:170427
[St] Status:MEDLINE


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[PMID]:28279169
[Au] Autor:Keiner S; Niv F; Neumann S; Steinbach T; Schmeer C; Hornung K; Schlenker Y; Förster M; Witte OW; Redecker C
[Ad] Endereço:Hans Berger Department of Neurology, Jena University Hospital, Am Klinikum 1, 07747, Jena, Germany. silke.keiner@med.uni-jena.de.
[Ti] Título:Effect of skilled reaching training and enriched environment on generation of oligodendrocytes in the adult sensorimotor cortex and corpus callosum.
[So] Source:BMC Neurosci;18(1):31, 2017 Mar 09.
[Is] ISSN:1471-2202
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Increased motor activity or social interactions through enriched environment are strong stimulators of grey and white matter plasticity in the adult rodent brain. In the present study we evaluated whether specific reaching training of the dominant forelimb (RT) and stimulation of unspecific motor activity through enriched environment (EE) influence the generation of distinct oligodendrocyte subpopulations in the sensorimotor cortex and corpus callosum of the adult rat brain. Animals were placed in three different housing conditions: one group was transferred to an EE, a second group received daily RT, whereas a third group remained in the standard cage. Bromodeoxyuridine (BrdU) was applied at days 2-6 after start of experiments and animals were allowed to survive for 10 and 42 days. RESULTS: Enriched environment and daily reaching training of the dominant forelimb significantly increased the number of newly differentiated GSTπ oligodendrocytes at day 10 and newly differentiated CNPase oligodendrocytes in the sensorimotor cortex at day 42. The myelin level as measured by CNPase expression was increased in the frontal cortex at day 42. Distribution of newly differentiated NG2 subpopulations changed between 10 and 42 days with an increase of GSTπ subtypes and a decrease of NG2 cells in the sensorimotor cortex and corpus callosum. Analysis of neuronal marker doublecortin (DCX) showed that more than half of NG2 cells express DCX in the cortex. The number of new DCX NG2 cells was reduced by EE at day 10. CONCLUSIONS: Our results indicate for the first time that specific and unspecific motor training conditions differentially alter the process of differentiation from oligodendrocyte subpopulations, in particular NG2 DCX cells, in the sensorimotor cortex and corpus callosum.
[Mh] Termos MeSH primário: Corpo Caloso/fisiologia
Abrigo para Animais
Destreza Motora/fisiologia
Oligodendroglia/fisiologia
Prática (Psicologia)
Córtex Sensório-Motor/fisiologia
[Mh] Termos MeSH secundário: 2',3'-Nucleotídeo Cíclico Fosfodiesterases/metabolismo
Animais
Antígenos/metabolismo
Bromodesoxiuridina
Corpo Caloso/citologia
Membro Anterior/fisiologia
Lobo Frontal/citologia
Lobo Frontal/fisiologia
Masculino
Proteínas Associadas aos Microtúbulos/metabolismo
Modelos Animais
Neurogênese/fisiologia
Neuropeptídeos/metabolismo
Oligodendroglia/citologia
Proteoglicanas/metabolismo
Distribuição Aleatória
Ratos Wistar
Tempo de Reação
Córtex Sensório-Motor/citologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens); 0 (Microtubule-Associated Proteins); 0 (Neuropeptides); 0 (Proteoglycans); 0 (chondroitin sulfate proteoglycan 4); 0 (doublecortin protein); EC 3.1.4.- (2',3'-Cyclic-Nucleotide Phosphodiesterases); G34N38R2N1 (Bromodeoxyuridine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170918
[Lr] Data última revisão:
170918
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170311
[St] Status:MEDLINE
[do] DOI:10.1186/s12868-017-0347-2


  4 / 1221 MEDLINE  
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[PMID]:28106876
[Au] Autor:Dey RJ; Dey B; Zheng Y; Cheung LS; Zhou J; Sayre D; Kumar P; Guo H; Lamichhane G; Sintim HO; Bishai WR
[Ad] Endereço:Center for Tuberculosis Research, Johns Hopkins University, Baltimore, Maryland, USA.
[Ti] Título:Inhibition of innate immune cytosolic surveillance by an M. tuberculosis phosphodiesterase.
[So] Source:Nat Chem Biol;13(2):210-217, 2017 Feb.
[Is] ISSN:1552-4469
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mycobacterium tuberculosis infection leads to cytosolic release of the bacterial cyclic dinucleotide (CDN) c-di-AMP and a host-generated CDN, cGAMP, both of which trigger type I interferon (IFN) expression in a STING-dependent manner. Here we report that M. tuberculosis has developed a mechanism to inhibit STING activation and the type I IFN response via the bacterial phosphodiesterase (PDE) CdnP, which mediates hydrolysis of both bacterial-derived c-di-AMP and host-derived cGAMP. Mutation of cdnP attenuates M. tuberculosis virulence, as does loss of a host CDN PDE known as ENPP1. CdnP is inhibited by both US Food and Drug Administration (FDA)-approved PDE inhibitors and nonhydrolyzable dinucleotide mimetics specifically designed to target the enzyme. These findings reveal a crucial role of CDN homeostasis in governing the outcome of M. tuberculosis infection as well as a unique mechanism of subversion of the host's cytosolic surveillance pathway (CSP) by a bacterial PDE that may serve as an attractive antimicrobial target.
[Mh] Termos MeSH primário: 2´,3´-Nucleotídeo Cíclico Fosfodiesterases/metabolismo
Citosol/imunologia
Citosol/microbiologia
Imunidade Inata
Mycobacterium tuberculosis/enzimologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 3.1.4.- (2',3'-Cyclic-Nucleotide Phosphodiesterases)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170509
[Lr] Data última revisão:
170509
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170121
[St] Status:MEDLINE
[do] DOI:10.1038/nchembio.2254


  5 / 1221 MEDLINE  
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[PMID]:27302679
[Au] Autor:Sandhu MS; Ross HH; Lee KZ; Ormerod BK; Reier PJ; Fuller DD
[Ad] Endereço:University of Florida, Department of Physical Therapy, P.O. Box 100154, Gainesville, FL 32610-0154, United States.
[Ti] Título:Intraspinal transplantation of subventricular zone-derived neural progenitor cells improves phrenic motor output after high cervical spinal cord injury.
[So] Source:Exp Neurol;287(Pt 2):205-215, 2017 Jan.
[Is] ISSN:1090-2430
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Following spinal cord injury (SCI), intraspinal transplantation of neural progenitor cells (NPCs) harvested from the forebrain sub-ventricular zone (SVZ) can improve locomotor outcomes. Cervical SCI often results in respiratory-related impairments, and here we used an established model cervical SCI (C2 hemisection, C2Hx) to confirm the feasibility of mid-cervical transplantation of SVZ-derived NPCs and the hypothesis that that this procedure would improve spontaneous respiratory motor recovery. NPCs were isolated from the SVZ of enhanced green fluorescent protein (GFP) expressing neonatal rats, and then intraspinally delivered immediately caudal to an acute C2Hx lesion in adult non-GFP rats. Whole body plethysmography conducted at 4 and 8wks post-transplant demonstrated increased inspiratory tidal volume in SVZ vs. sham transplants during hypoxic (P=0.003) or hypercapnic respiratory challenge (P=0.019). Phrenic nerve output was assessed at 8wks post-transplant; burst amplitude recorded ipsilateral to C2Hx was greater in SVZ vs. sham rats across a wide range of conditions (e.g., quiet breathing through maximal chemoreceptor stimulation; P<0.001). Stereological analyses at 8wks post-injury indicated survival of ~50% of transplanted NPCs with ~90% of cells distributed in ipsilateral white matter at or near the injection site. Peak inspiratory phrenic bursting after NPC transplant was positively correlated with the total number of surviving cells (P<0.001). Immunohistochemistry confirmed an astrocytic phenotype in a subset of the transplanted cells with no evidence for neuronal differentiation. We conclude that intraspinal transplantation of SVZ-derived NPCs can improve respiratory recovery following high cervical SCI.
[Mh] Termos MeSH primário: Ventrículos Laterais/citologia
Nervo Frênico/fisiologia
Transtornos Respiratórios/etiologia
Traumatismos da Medula Espinal/complicações
Traumatismos da Medula Espinal/cirurgia
[Mh] Termos MeSH secundário: 2',3'-Nucleotídeo Cíclico Fosfodiesterases/metabolismo
Animais
Animais Recém-Nascidos
Antígeno CD11b/metabolismo
Vértebras Cervicais
Modelos Animais de Doenças
Feminino
Proteína Glial Fibrilar Ácida/metabolismo
Proteínas de Fluorescência Verde/genética
Proteínas de Fluorescência Verde/metabolismo
Hipóxia
Masculino
Proteína Básica da Mielina/metabolismo
Células-Tronco Neurais/metabolismo
Células-Tronco Neurais/fisiologia
Ratos
Ratos Sprague-Dawley
Ratos Transgênicos
Recuperação de Função Fisiológica/fisiologia
Transtornos Respiratórios/cirurgia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CD11b Antigen); 0 (Glial Fibrillary Acidic Protein); 0 (Myelin Basic Protein); 0 (enhanced green fluorescent protein); 147336-22-9 (Green Fluorescent Proteins); EC 3.1.4.- (2',3'-Cyclic-Nucleotide Phosphodiesterases)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160616
[St] Status:MEDLINE


  6 / 1221 MEDLINE  
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[PMID]:28269202
[Au] Autor:Joshi R; Buchanan J; Tavana H
[Ti] Título:Colony size effect on neural differentiation of embryonic stem cells microprinted on stromal cells.
[So] Source:Conf Proc IEEE Eng Med Biol Soc;2016:4173-4176, 2016 08.
[Is] ISSN:1557-170X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Controlling cellular microenvironment to induce neural differentiation of embryonic stem cells (ESCs) remains a major challenge. We address this need by introducing a micro-engineered co-culture system that resembles embryonic development in terms of direct intercellular interactions and induces neural differentiation of ESCs. A polymeric aqueous two-phase system (ATPS)-mediated robotic microprinting technology allows precise localization of mouse ESCs (mESCs) over a layer of supporting stromal cells. mESCs proliferate over a 2-week culture period into a single colony of defined size. Physical and chemical cues from the stromal cells guide mESCs to differentiate toward specific neural lineages. We generated mESC colonies of three different sizes from 100, 250 and 500 single cells and showed that size of mESC colonies is an important factor determining the yield of neural cells. Expression of early neural cell markers nestin denoting neural stem cells, NCAM specifying neural progenitors, and ß-III tubulin (TuJ) indicating post mitotic neurons escalated from day 4. Differentiation into specific neural cells astrocytes marked by GFAP, oligodendrocytes indicated by CNPase, and TH-positive dopaminergic neurons was observed during the second week of culture. Unexpectedly, analysis of protein expression revealed a disproportionate increase in neural differentiation of mESCs by increase in the colony size. For the first time, our study establishes colony size as an important regulator of fate of ESCs in this heterocellular niche. This approach of deriving neural cells may make a major impact on stem cell research for treating neurodegenerative diseases.
[Mh] Termos MeSH primário: Células-Tronco Embrionárias Murinas/citologia
Células Estromais/citologia
[Mh] Termos MeSH secundário: 2',3'-Nucleotídeo Cíclico Fosfodiesterases/metabolismo
Animais
Diferenciação Celular
Células Cultivadas
Técnicas de Cocultura
Camundongos
Microscopia de Fluorescência
Células-Tronco Embrionárias Murinas/metabolismo
Nestina/metabolismo
Neurônios/citologia
Neurônios/metabolismo
Oligodendroglia/metabolismo
Células Estromais/metabolismo
Tubulina (Proteína)/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Nestin); 0 (Tubulin); EC 3.1.4.- (2',3'-Cyclic-Nucleotide Phosphodiesterases)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171122
[Lr] Data última revisão:
171122
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170309
[St] Status:MEDLINE
[do] DOI:10.1109/EMBC.2016.7591646


  7 / 1221 MEDLINE  
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[PMID]:27587342
[Au] Autor:Dincman TA; Beare JE; Ohri SS; Gallo V; Hetman M; Whittemore SR
[Ad] Endereço:Division of Hematology & Oncology, Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, United States.
[Ti] Título:Histone deacetylase inhibition is cytotoxic to oligodendrocyte precursor cells in vitro and in vivo.
[So] Source:Int J Dev Neurosci;54:53-61, 2016 Nov.
[Is] ISSN:1873-474X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Histone deacetylase (HDAC) inhibition mediated by small molecule HDAC inhibitors (HDACi) has demonstrated divergent effects including toxicity towards transformed cell lines, neuroprotection in neurological disease models, and inhibition of oligodendrocyte precursor cell (OPC) differentiation to mature oligodendrocytes (OL). However, it remains unknown if transient HDAC inhibition may promote OPC survival. Using mouse cortical OPC primary cultures, we investigated the effects of the FDA approved pan-HDACi suberoylanilide hydroxamic acid (SAHA) on OPC survival. Initial studies showed differences in the HDAC expression pattern of multiple HDAC isoforms in OPCs relative to their terminally differentiated progeny cells, OLs and astrocytes. Treatment of OPCs with SAHA for up to 72h using a maximum concentration either at or lower than those necessary for cytotoxicity in most transformed cell lines resulted in over 67% reduction in viability relative to vehicle-treated OPCs. This was at least partly due to increased apoptosis as SAHA-treated cells displayed activated caspase 3 and were protected by the general caspase inhibitor Q-VD-OPH. Additionally, SAHA treatment of whole mice at postnatal day 5 induced apoptosis of cortical OPCs. These results suggest that SAHA negatively impacts OPC survival and may be detrimental to the myelinating brain and spinal cord. Such toxicity may be relevant in a clinical context as SAHA is currently involved in numerous clinical trials and is in consideration for use in the treatment of psychiatric and neurodegenerative conditions.
[Mh] Termos MeSH primário: Regulação da Expressão Gênica no Desenvolvimento/fisiologia
Histona Desacetilases/metabolismo
Oligodendroglia/enzimologia
Células-Tronco/fisiologia
[Mh] Termos MeSH secundário: 2',3'-Nucleotídeo Cíclico Fosfodiesterases/genética
2',3'-Nucleotídeo Cíclico Fosfodiesterases/metabolismo
Animais
Animais Recém-Nascidos
Caspases/metabolismo
Proliferação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Células Cultivadas
Córtex Cerebral/citologia
Relação Dose-Resposta a Droga
Embrião de Mamíferos
Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos
Inibidores de Histona Desacetilases/farmacologia
Histona Desacetilases/genética
Ácidos Hidroxâmicos/farmacologia
Técnicas In Vitro
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Oligodendroglia/efeitos dos fármacos
Células-Tronco/efeitos dos fármacos
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Histone Deacetylase Inhibitors); 0 (Hydroxamic Acids); 58IFB293JI (vorinostat); EC 3.1.4.- (2',3'-Cyclic-Nucleotide Phosphodiesterases); EC 3.4.22.- (Caspases); EC 3.5.1.98 (Histone Deacetylases)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170327
[Lr] Data última revisão:
170327
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160903
[St] Status:MEDLINE


  8 / 1221 MEDLINE  
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[PMID]:27294396
[Au] Autor:López-Villamizar I; Cabezas A; Pinto RM; Canales J; Ribeiro JM; Cameselle JC; Costas MJ
[Ad] Endereço:Grupo de Enzimología, Departamento de Bioquímica y Biología Molecular y Genética, Facultad de Medicina, Universidad de Extremadura, Badajoz, Spain.
[Ti] Título:The Characterization of Escherichia coli CpdB as a Recombinant Protein Reveals that, besides Having the Expected 3´-Nucleotidase and 2´,3´-Cyclic Mononucleotide Phosphodiesterase Activities, It Is Also Active as Cyclic Dinucleotide Phosphodiesterase.
[So] Source:PLoS One;11(6):e0157308, 2016.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Endogenous cyclic diadenylate phosphodiesterase activity was accidentally detected in lysates of Escherichia coli BL21. Since this kind of activity is uncommon in Gram-negative bacteria, its identification was undertaken. After partial purification and analysis by denaturing gel electrophoresis, renatured activity correlated with a protein identified by fingerprinting as CpdB (cpdB gene product), which is annotated as 3´-nucleotidase / 2´,3´-cyclic-mononucleotide phosphodiesterase, and it is synthesized as a precursor protein with a signal sequence removable upon export to the periplasm. It has never been studied as a recombinant protein. The coding sequence of mature CpdB was cloned and expressed as a GST fusion protein. The study of the purified recombinant protein, separated from GST, confirmed CpdB annotation. The assay of catalytic efficiencies (kcat/Km) for a large substrate set revealed novel CpdB features, including very high efficiencies for 3´-AMP and 2´,3´-cyclic mononucleotides, and previously unknown activities on cyclic and linear dinucleotides. The catalytic efficiencies of the latter activities, though low in relative terms when compared to the major ones, are far from negligible. Actually, they are perfectly comparable to those of the 'average' enzyme and the known, bona fide cyclic dinucleotide phosphodiesterases. On the other hand, CpdB differs from these enzymes in its extracytoplasmic location and in the absence of EAL, HD and DHH domains. Instead, it contains the domains of the 5´-nucleotidase family pertaining to the metallophosphoesterase superfamily, although CpdB lacks 5´-nucleotidase activity. The possibility that the extracytoplasmic activity of CpdB on cyclic dinucleotides could have physiological meaning is discussed.
[Mh] Termos MeSH primário: 2´,3´-Nucleotídeo Cíclico Fosfodiesterases/metabolismo
Proteínas de Escherichia coli/metabolismo
Escherichia coli/metabolismo
Nucleotidases/metabolismo
Nucleotídeos Cíclicos/metabolismo
Diester Fosfórico Hidrolases/metabolismo
[Mh] Termos MeSH secundário: 2',3'-Nucleotídeo Cíclico Fosfodiesterases/genética
3',5'-AMP Cíclico Fosfodiesterases/genética
3',5'-AMP Cíclico Fosfodiesterases/metabolismo
Clonagem Molecular
Escherichia coli/genética
Proteínas de Escherichia coli/genética
Nucleotidases/genética
Diester Fosfórico Hidrolases/genética
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Escherichia coli Proteins); 0 (Nucleotides, Cyclic); 0 (Recombinant Proteins); EC 3.1.3.- (Nucleotidases); EC 3.1.3.6 (3'-nucleotidase); EC 3.1.4.- (2',3'-Cyclic-Nucleotide Phosphodiesterases); EC 3.1.4.- (CpdB protein, E coli); EC 3.1.4.- (Phosphoric Diester Hydrolases); EC 3.1.4.17 (3',5'-Cyclic-AMP Phosphodiesterases)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170718
[Lr] Data última revisão:
170718
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160614
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0157308


  9 / 1221 MEDLINE  
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[PMID]:26943953
[Au] Autor:Makar TK; Nimmagadda VK; Singh IS; Lam K; Mubariz F; Judge SI; Trisler D; Bever CT
[Ad] Endereço:Department of Neurology, University of Maryland, Baltimore, MD 21201, United States; Research Service, VA Medical Center, Baltimore, MD 21201, United States; VA Multiple Sclerosis Center of Excellence East, Baltimore, MD 21201, United States. Electronic address: tmakar@som.umaryland.edu.
[Ti] Título:TrkB agonist, 7,8-dihydroxyflavone, reduces the clinical and pathological severity of a murine model of multiple sclerosis.
[So] Source:J Neuroimmunol;292:9-20, 2016 Mar 15.
[Is] ISSN:1872-8421
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:7,8-Dihydroxyflavone (DHF), is a recently described TrkB agonist that readily crosses the blood brain barrier. We treated C57Bl/6 mice with MOG--induced EAE daily with DHF starting on the day of disease induction. Clinical severity of impairment was reduced throughout the course of disease. Pathological examination of brains and spinal cords on day 28 showed that DHF treatment increased the phosphorylation of TrkB and activated downstream signaling pathways including AKT and STAT3 and reduced inflammation, demyelination and axonal loss compared to EAE controls. DHF treatment duplicated the central nervous system effects of brain derived neurotrophic factor in the EAE.
[Mh] Termos MeSH primário: Encéfalo/patologia
Encefalomielite Autoimune Experimental/tratamento farmacológico
Encefalomielite Autoimune Experimental/patologia
Flavonas/uso terapêutico
Esclerose Múltipla/tratamento farmacológico
Medula Espinal/patologia
[Mh] Termos MeSH secundário: 2',3'-Nucleotídeo Cíclico Fosfodiesterases/metabolismo
Animais
Apoptose/efeitos dos fármacos
Encéfalo/efeitos dos fármacos
Encéfalo/metabolismo
Citocinas/metabolismo
Modelos Animais de Doenças
Encefalomielite Autoimune Experimental/imunologia
Feminino
Seres Humanos
Camundongos
Camundongos Endogâmicos C57BL
Proteína Básica da Mielina/metabolismo
Glicoproteína Mielina-Oligodendrócito/toxicidade
Fragmentos de Peptídeos/toxicidade
Índice de Gravidade de Doença
Transdução de Sinais/efeitos dos fármacos
Medula Espinal/efeitos dos fármacos
Medula Espinal/metabolismo
Fatores de Tempo
Proteína X Associada a bcl-2/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (6,7-dihydroxyflavone); 0 (Cytokines); 0 (Flavones); 0 (Myelin Basic Protein); 0 (Myelin-Oligodendrocyte Glycoprotein); 0 (Peptide Fragments); 0 (bcl-2-Associated X Protein); 0 (myelin oligodendrocyte glycoprotein (35-55)); EC 3.1.4.- (2',3'-Cyclic-Nucleotide Phosphodiesterases)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:170216
[Lr] Data última revisão:
170216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160306
[St] Status:MEDLINE


  10 / 1221 MEDLINE  
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[PMID]:26791522
[Au] Autor:Ruiz-Mendoza S; Macedo-Ramos H; Santos FA; Quadros-de-Souza LC; Paiva MM; Pinto TC; Teixeira LM; Baetas-da-Cruz W
[Ad] Endereço:Laboratório Translacional em Fisiologia Molecular, Centro de Cirurgia Experimental, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil; Instituto de Biofísica Carlos Chagas Filho, Programa de Pós-Graduação em Ciências Biológicas (Fisiologia), Universidade Feder
[Ti] Título:Streptococcus pneumoniae infection regulates expression of neurotrophic factors in the olfactory bulb and cultured olfactory ensheathing cells.
[So] Source:Neuroscience;317:149-61, 2016 Mar 11.
[Is] ISSN:1873-7544
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Streptococcus pneumoniae is the causative agent of numerous diseases including severe invasive infections such as bacteremia and meningitis. It has been previously shown that strains of S. pneumoniae that are unable to survive in the bloodstream may colonize the CNS. However, information on cellular components and pathways involved in the neurotropism of these strains is still scarce. The olfactory system is a specialized tissue in which olfactory receptor neurons (ORNs) are interfacing with the external environment through several microvilli. Olfactory ensheathing cells (OECs) which also form the glial limiting membrane at the surface of the olfactory bulb (OB) are the only cells that ensheathe the ORNs axons. Since previous data from our group showed that OECs may harbor S. pneumoniae, we decided to test whether infection of the OB or OEC cultures modulates the expression levels of neurotrophic factor's mRNA and its putative effects on the activation and viability of microglia. We observed that neurotrophin-3 (NT-3) and glial cell-line-derived neurotrophic factor (GDNF) expression was significantly higher in the OB from uninfected mice than in infected mice. A similar result was observed when we infected OEC cultures. Brain-derived neurotrophic factor (BNDF) expression was significantly lower in the OB from infected mice than in uninfected mice. In contrast, in vitro infection of OECs resulted in a significant increase of BDNF mRNA expression. An upregulation of high-mobility group box 1 (HMGB1) expression was observed in both OB and OEC cultures infected with S. pneumoniae. Moreover, we found that conditioned medium from infected OEC cultures induced the expression of the pro-apoptotic protein cleaved-caspase-3 and an apparently continuous nuclear factor-kappa B (NF-κB) p65 activation in the N13 microglia. Altogether, our data suggest the possible existence of an OEC-pathogen molecular interface, through which the OECs could interfere on the activation and viability of microglia, favoring the access of non-hematogenous S. pneumoniae strains to the CNS in the absence of bacteremia.
[Mh] Termos MeSH primário: Fatores de Crescimento Neural/metabolismo
Neuroglia/metabolismo
Bulbo Olfatório/metabolismo
Bulbo Olfatório/patologia
Infecções Pneumocócicas/patologia
[Mh] Termos MeSH secundário: 2',3'-Nucleotídeo Cíclico Fosfodiesterases/metabolismo
Actinas/metabolismo
Animais
Caspase 3/metabolismo
Células Cultivadas
Modelos Animais de Doenças
Regulação Bacteriana da Expressão Gênica/fisiologia
Proteína HMGB1/genética
Proteína HMGB1/metabolismo
Masculino
Camundongos
Camundongos Endogâmicos BALB C
Modelos Biológicos
N-Acetil-Muramil-L-Alanina Amidase/genética
N-Acetil-Muramil-L-Alanina Amidase/metabolismo
NF-kappa B/metabolismo
Fatores de Crescimento Neural/genética
Neuroglia/microbiologia
RNA Mensageiro/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Actins); 0 (HMGB1 Protein); 0 (HMGB1 protein, mouse); 0 (NF-kappa B); 0 (Nerve Growth Factors); 0 (RNA, Messenger); EC 3.1.4.- (2',3'-Cyclic-Nucleotide Phosphodiesterases); EC 3.4.22.- (Caspase 3); EC 3.5.1.28 (N-Acetylmuramoyl-L-alanine Amidase)
[Em] Mês de entrada:1610
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160122
[St] Status:MEDLINE



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