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[PMID]:28987405
[Au] Autor:Botelho MJ; Vale C; Joaquim S; Costa ST; Soares F; Roque C; Matias D
[Ad] Endereço:IPMA, Portuguese Institute for the Sea and Atmosphere, Rua Alfredo Magalhães Ramalho, 6, 1495-006, Lisbon, Portugal; CIIMAR, Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Rua dos Bragas 289, 4050-123, Porto, Portugal. Electronic address: mjbotelho@ipma.pt.
[Ti] Título:Combined effect of temperature and nutritional regime on the elimination of the lipophilic toxin okadaic acid in the naturally contaminated wedge shell Donax trunculus.
[So] Source:Chemosphere;190:166-173, 2018 Jan.
[Is] ISSN:1879-1298
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The influence of nutritional regime and water temperature on depuration rates of OA-group toxins in the wedge shell Donax trunculus was examined by exposing naturally contaminated specimens to three nutritional regimes (microalgae, commercial paste of microalgae, and starvation) for 14 days at 16 °C and 20 °C. Total OA was quantified in the whole soft tissues of the individuals collected in days 2, 4, 6, 8, 10, 12 and 14. Mortality, dry weight, condition index, gross biochemical composition and gametogenic stages were surveyed. Low variation of glycogen and carbohydrates during the experiments suggest that wedge shells were under non-dramatic stress conditions. Wedge shells fed with non-toxic diets showed similar depuration rates being 15 and 38% higher than in starvation, at 16 and 20 °C, respectively. Depuration rates under non-toxic diets at 20 °C were 71% higher than at 16 °C. These results highlight the influence of water temperature on the depuration rate of total OA accumulated by D. trunculus, even when the increase is of only 4 °C, as commonly observed in week time scales in the southern Portuguese coastal waters. These results open the possibility of a faster release of OA in harvested wedge shells translocated to depuration systems when under a slight increase of water temperature.
[Mh] Termos MeSH primário: Bivalves/química
Recuperação e Remediação Ambiental/métodos
Avaliação Nutricional
Ácido Okadáico/isolamento & purificação
Temperatura Ambiente
[Mh] Termos MeSH secundário: Animais
Carboidratos/análise
Dieta/efeitos adversos
Glicogênio/análise
Toxinas Marinhas/isolamento & purificação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carbohydrates); 0 (Marine Toxins); 1W21G5Q4N2 (Okadaic Acid); 9005-79-2 (Glycogen)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171009
[St] Status:MEDLINE


  2 / 3570 MEDLINE  
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[PMID]:28419442
[Au] Autor:Arumugam B; Vairamani M; Partridge NC; Selvamurugan N
[Ad] Endereço:Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur, Tamil Nadu, India.
[Ti] Título:Characterization of Runx2 phosphorylation sites required for TGF-ß1-mediated stimulation of matrix metalloproteinase-13 expression in osteoblastic cells.
[So] Source:J Cell Physiol;233(2):1082-1094, 2018 Feb.
[Is] ISSN:1097-4652
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Transforming growth factor-beta1 (TGF-ß1), a highly abundant growth factor in skeletal tissues, stimulates matrix metalloproteinase-13 (MMP-13) expression in osteoblastic cells. MMP-13 plays a critical role in bone remodeling. Runx2, a bone transcription factor, is required for TGF-ß1-mediated stimulation of MMP-13 expression in osteoblastic cells. In this study, the molecular mechanism responsible for TGF-ß1-stimulation of MMP-13 expression via Runx2 in osteoblastic cells was elucidated. TGF-ß1 stimulated the phosphorylation of Runx2 at serine amino acids, and ERK inhibition blocked this effect in rat (UMR106-01) and human (MG-63) osteoblastic cells. Pretreatment with okadaic acid, a serine-threonine phosphatase inhibitor, increased Runx2 serine phosphorylation in osteoblastic cells. When cells were pretreated with an ERK inhibitor, TGF-ß1-mediated stimulation of MMP-13 mRNA expression decreased. Nano-ESI/LC/MS analysis identified that TGF-ß1 stimulates Runx2 phosphorylation at three serine amino acids. Transient transfection of mouse mesenchymal stem cells (C3H10T1/2) with Runx2 serine mutant constructs decreased TGF-ß1-mediated Runx2 serine phosphorylation. A luciferase reporter assay identified that TGF-ß1 stimulated MMP-13 promoter activity in these cells only in the presence of the wild Runx2 construct, and not with mutant Runx2. Thus, TGF-ß1 stimulates the phosphorylation of Runx2 at three serine amino acids, and this event is required for MMP-13 expression in osteoblastic cells. Hence, this study contributes to the knowledge of events governing bone remodeling and bone-related diseases.
[Mh] Termos MeSH primário: Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo
Metaloproteinase 13 da Matriz/biossíntese
Osteoblastos/efeitos dos fármacos
Fator de Crescimento Transformador beta1/farmacologia
[Mh] Termos MeSH secundário: Animais
Remodelação Óssea/efeitos dos fármacos
Linhagem Celular
Subunidade alfa 1 de Fator de Ligação ao Core/genética
Indução Enzimática
MAP Quinases Reguladas por Sinal Extracelular/metabolismo
Seres Humanos
Metaloproteinase 13 da Matriz/genética
Células Mesenquimais Estromais/efeitos dos fármacos
Células Mesenquimais Estromais/enzimologia
Camundongos Endogâmicos C3H
Mutação
Ácido Okadáico/farmacologia
Osteoblastos/enzimologia
Osteogênese/efeitos dos fármacos
Fosforilação
Regiões Promotoras Genéticas
Ratos
Transdução de Sinais/efeitos dos fármacos
Transcrição Genética/efeitos dos fármacos
Ativação Transcricional/efeitos dos fármacos
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Core Binding Factor Alpha 1 Subunit); 0 (RUNX2 protein, human); 0 (Runx2 protein, mouse); 0 (Runx2 protein, rat); 0 (Transforming Growth Factor beta1); 1W21G5Q4N2 (Okadaic Acid); EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases); EC 3.4.24.- (MMP13 protein, human); EC 3.4.24.- (Matrix Metalloproteinase 13); EC 3.4.24.- (Mmp13 protein, mouse); EC 3.4.24.- (Mmp13 protein, rat)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171128
[Lr] Data última revisão:
171128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170419
[St] Status:MEDLINE
[do] DOI:10.1002/jcp.25964


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[PMID]:28634074
[Au] Autor:Fukuchi M; Sanabe T; Watanabe T; Kubota T; Tabuchi A; Tsuda M
[Ad] Endereço:Laboratory of Molecular Neuroscience, Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi, Takasaki-shi, Gunma 370-0033, Japan; Department of Biological Chemistry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama-shi,
[Ti] Título:Distinct regulation of activity-dependent transcription of immediate early genes in cultured rat cortical neurons.
[So] Source:Biochem Biophys Res Commun;490(3):682-687, 2017 Aug 26.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The activity-regulated expression of immediate early genes (IEGs) contributes to long-lasting neuronal functions underlying long-term memory. However, their response properties following neuronal activity are unique and remain poorly understood. To address this knowledge gap, here we further investigated the response properties of two representative IEGs, c-fos and brain-derived neurotrophic factor (Bdnf). Treatment of cultured cortical cells with KCl produces a depolarization process that results in the increase of intracellular calcium concentration in a KCl concentration-dependent manner. Consistent with this increase, c-fos expression was induced in a KCl concentration-dependent manner. In contrast, however, Bdnf expression was optimally activated by both 25 and 50 mM concentration of KCl. Similar results were observed when the cells were treated with okadaic acid, which inhibits protein phosphatases and elicits the hyper-phosphorylation of signaling molecules. Thus, Bdnf expression is strictly regulated by a neuronal activity threshold in an all or nothing manner, whereas c-fos expression is activated in a neuronal activity-dependent manner. Our findings also suggest that these differential responses might be due to the presence or absence of a TATA box.
[Mh] Termos MeSH primário: Fator Neurotrófico Derivado do Encéfalo/genética
Genes Precoces
Neurônios/metabolismo
Proteínas Proto-Oncogênicas c-fos/genética
Ativação Transcricional
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
MAP Quinases Reguladas por Sinal Extracelular/metabolismo
Memória de Longo Prazo
Neurônios/citologia
Ácido Okadáico/metabolismo
Fosforilação
Cloreto de Potássio/metabolismo
Ratos
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Brain-Derived Neurotrophic Factor); 0 (Proto-Oncogene Proteins c-fos); 1W21G5Q4N2 (Okadaic Acid); 660YQ98I10 (Potassium Chloride); EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170811
[Lr] Data última revisão:
170811
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170622
[St] Status:MEDLINE


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[PMID]:28586109
[Au] Autor:Ramírez-Valadez KA; Vázquez-Victorio G; Macías-Silva M; González-Espinosa C
[Ad] Endereço:Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados del IPN, México.
[Ti] Título:Fyn kinase mediates cortical actin ring depolymerization required for mast cell migration in response to TGF-ß in mice.
[So] Source:Eur J Immunol;47(8):1305-1316, 2017 Aug.
[Is] ISSN:1521-4141
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Transforming growth factor-ß (TGF-ß) is a potent mast cell (MC) chemoattractant able to modulate local inflammatory reactions. The molecular mechanism leading to TGF-ß-directed MC migration is not fully described. Here we analyzed the role of the Src family protein kinase Fyn on the main TGF-ß-induced cytoskeletal changes leading to MC migration. Utilizing bone marrow-derived mast cells (BMMCs) from WT and Fyn-deficient mice we found that BMMC migration to TGF-ß was impaired in the absence of the kinase. TGF-ß caused depolymerization of the cortical actin ring and changes on the phosphorylation of cofilin, LIMK and CAMKII only in WT cells. Defective cofilin activation and phosphorylation of regulatory proteins was detected in Fyn-deficient BMMCs and this finding correlated with a lower activity of the catalytic subunit of the phosphatase PP2A. Diminished TGF-ß-induced chemotaxis of Fyn-deficient cells was also observed in an in vivo model of MC migration (bleomycin-induced scleroderma). Our results show that Fyn kinase is an important positive effector of TGF-ß-induced chemotaxis through the control of PP2A activity and this is relevant to pathological processes that are related to TGF-ß-dependent mast cell migration.
[Mh] Termos MeSH primário: Actinas/metabolismo
Quimiotaxia
Mastócitos/fisiologia
Proteínas Proto-Oncogênicas c-fyn/metabolismo
Fator de Crescimento Transformador beta/fisiologia
[Mh] Termos MeSH secundário: Fatores de Despolimerização de Actina/metabolismo
Animais
Mastócitos/imunologia
Camundongos
Ácido Okadáico/farmacologia
Fosforilação
Proteína Fosfatase 2/metabolismo
Proteínas Proto-Oncogênicas c-fyn/genética
Transdução de Sinais
Proteína Smad2/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Actin Depolymerizing Factors); 0 (Actins); 0 (Smad2 Protein); 0 (Smad2 protein, mouse); 0 (Transforming Growth Factor beta); 1W21G5Q4N2 (Okadaic Acid); EC 2.7.10.2 (Fyn protein, mouse); EC 2.7.10.2 (Proto-Oncogene Proteins c-fyn); EC 3.1.3.16 (Protein Phosphatase 2)
[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:170607
[St] Status:MEDLINE
[do] DOI:10.1002/eji.201646876


  5 / 3570 MEDLINE  
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[PMID]:28554022
[Au] Autor:Liu Y; Yu RC; Kong FZ; Li C; Dai L; Chen ZF; Zhou MJ
[Ad] Endereço:CAS Key Laboratory of Marine Ecology and Environmental Sciences, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, PR China; University of Chinese Academy of Sciences, Beijing 100039, PR China.
[Ti] Título:Lipophilic marine toxins discovered in the Bohai Sea using high performance liquid chromatography coupled with tandem mass spectrometry.
[So] Source:Chemosphere;183:380-388, 2017 Sep.
[Is] ISSN:1879-1298
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Some dinoflagellates can produce lipophilic marine toxins, which pose potent threats to seafood consumers. In the Bohai Sea, an important semi-closed inland sea with intensive mariculture industry in China, there is little knowledge concerning lipophilic marine toxins and their potential threats. In this study, net-concentrated phytoplankton samples were periodically collected from 5 typical mariculture zones around the Bohai Sea, including Laishan (LS), Laizhou (LZ), Hangu (HG), Qinhuangdao (QHD) and Huludao (HLD) in 2013 and 2014, and a method using high performance liquid chromatography (HPLC) coupled with a Q-Trap mass spectrometer was applied to analyze seven representative lipophilic marine toxins, including okadaic acid (OA), dinophysistoxin-1 (DTX1), pectenotoxin-2 (PTX2), yessotoxin (YTX), azaspiracid-1 (AZA1), gymnodimine (GYM), and 13-desmethyl spirolide C (desMeC). The method had high sensitivity and repeatability, and exhibited satisfactory recoveries for most of the lipophilic marine toxins (92.1-108%) except for AZA1 (65.8-68.9%). Nearly all the lipophilic marine toxins could be detected in phytoplankton samples from the Bohai Sea. OA, DTX1 and PTX2 were predominant components and present in most of the phytoplankton samples. The maximum content of lipophilic marine toxin in phytoplankton samples concentrated from seawater (OA 464 pg L ; DTX1 783 pg L ; YTX 86.6 pg L ; desMeC 15.6 pg L ; PTX2 1.11 × 10 pg L ) appeared in June 2014. Based on toxins present in phytoplankton samples, it is implied that seafood in the Bohai Sea is more likely to be contaminated by OA group and PTX group toxins, and spring is the high-risk season for toxin contamination.
[Mh] Termos MeSH primário: Dinoflagelados/química
Toxinas Marinhas/análise
Fitoplâncton/química
Alimentos Marinhos/normas
[Mh] Termos MeSH secundário: Animais
China
Cromatografia Líquida de Alta Pressão/métodos
Furanos/análise
Compostos Heterocíclicos com 3 Anéis/análise
Hidrocarbonetos Cíclicos/análise
Interações Hidrofóbicas e Hidrofílicas
Iminas/análise
Ácido Okadáico/análise
Oxocinas/análise
Piranos/análise
Alimentos Marinhos/análise
Compostos de Espiro/análise
Espectrometria de Massas em Tandem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (13-desmethylspirolide C); 0 (Furans); 0 (Heterocyclic Compounds, 3-Ring); 0 (Hydrocarbons, Cyclic); 0 (Imines); 0 (Marine Toxins); 0 (Oxocins); 0 (Pyrans); 0 (Spiro Compounds); 0 (azaspiracid); 1W21G5Q4N2 (Okadaic Acid); 4Q51CVY9O2 (dinophysistoxin 1); 7TV3J97IT8 (gymnodimine); 97564-91-5 (pectenotoxin 2); P6M9FM2L2G (yessotoxin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170530
[St] Status:MEDLINE


  6 / 3570 MEDLINE  
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[PMID]:28535464
[Au] Autor:Jiang T; Liu L; Li Y; Zhang J; Tan Z; Wu H; Jiang T; Lu S
[Ad] Endereço:Key Laboratory of Sustainable Development of Marine Fisheries, Ministry of Agriculture, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China; Research Center for Harmful Algae & Marine Biology, Jinan University, Guangzhou 510632, China.
[Ti] Título:Occurrence of marine algal toxins in oyster and phytoplankton samples in Daya Bay, South China Sea.
[So] Source:Chemosphere;183:80-88, 2017 Sep.
[Is] ISSN:1879-1298
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The occurrence and seasonal variations of marine algal toxins in phytoplankton and oyster samples in Daya Bay (DYB), South China Sea were investigated. Two Dinophysis species, namely, D. caudata and D. acuminata complex, were identified as Okadaic acid (OA)/pectenotoxin (PTX) related species. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis demonstrated that 2.04-14.47 pg PTX2 per cell was the predominant toxin in single-cell isolates of D. caudata. D. acuminata was not subjected to toxin analysis. The occurrence of OAs in phytoplankton concentrates of net-haul sample coincided with the presence of D. accuminata complex, suggesting that this species is most likely an OA producer in this sea area. OA, dinophysistoxins-1 (DTX1), PTX2, PTX2sa, gymnodimine (GYM), homoyessotoxin (homoYTX), and domoic acid (DA) demonstrated positive results in net haul samples. To our best knowledge, this paper is the first to report the detection of GYM, DA, and homoYTX in phytoplankton samples in Chinese coastal waters. Among the algal toxins, GYM demonstrated the highest frequency of positive detections in phytoplankton concentrates (13/17). Five compounds of algal toxins, including OA, DTX1, PTX2, PTX2sa, and GYM, were detected in oyster samples. DA and homoYTX were not detected in oysters despite of positive detections for both in the phytoplankton concentrates. However, neither the presence nor absence of DA in oysters can be determined because extraction conditions with 100% methanol used to isolate toxins from oysters (recommended by the EU-Harmonised Standard Operating Procedure, 2015) would likely be unsuitable for this water-soluble toxin. In addition, transformation of DA during the digestion process of oysters may also be involved in the negative detections of this toxin. GYM exhibited the highest frequency of positive results in oysters (14/17). OAs were only detected in the hydrolyzed oyster samples. The detection rates of PTX and PTX2sa in oysters were lower than those in the net haul samples.
[Mh] Termos MeSH primário: Baías/química
Dinoflagelados/metabolismo
Monitoramento Ambiental/métodos
Toxinas Marinhas/análise
Ostreidae/química
Fitoplâncton/química
Poluentes Químicos da Água/análise
[Mh] Termos MeSH secundário: Animais
China
Cromatografia Líquida/métodos
Compostos Heterocíclicos com 3 Anéis/análise
Compostos Heterocíclicos com 3 Anéis/metabolismo
Hidrocarbonetos Cíclicos/análise
Hidrocarbonetos Cíclicos/metabolismo
Iminas/análise
Iminas/metabolismo
Ácido Caínico/análogos & derivados
Ácido Caínico/análise
Ácido Caínico/metabolismo
Toxinas Marinhas/metabolismo
Ácido Okadáico/análise
Ácido Okadáico/metabolismo
Ostreidae/metabolismo
Fitoplâncton/metabolismo
Piranos/análise
Piranos/metabolismo
Espectrometria de Massas em Tandem
Poluentes Químicos da Água/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Heterocyclic Compounds, 3-Ring); 0 (Hydrocarbons, Cyclic); 0 (Imines); 0 (Marine Toxins); 0 (Pyrans); 0 (Water Pollutants, Chemical); 1W21G5Q4N2 (Okadaic Acid); 4Q51CVY9O2 (dinophysistoxin 1); 7TV3J97IT8 (gymnodimine); M02525818H (domoic acid); SIV03811UC (Kainic Acid)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170524
[St] Status:MEDLINE


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[PMID]:28383915
[Au] Autor:Yang AR; Lee S; Yoo YD; Kim HS; Jeong EJ; Rho JR
[Ad] Endereço:Department of Marine Biotechnology, Kunsan National University , 558 Daehak-ro, Gunsan 54150, South Korea.
[Ti] Título:Limaol: A Polyketide from the Benthic Marine Dinoflagellate Prorocentrum lima.
[So] Source:J Nat Prod;80(5):1688-1692, 2017 May 26.
[Is] ISSN:1520-6025
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Limaol (1), along with a dinophysistoxin 1 derivative and an okadaic acid (OA) derivative, was isolated from the large-scale cultivation of the benthic marine dinoflagellate Prorocentrum lima. The structure of 1 was determined by a combination of NMR spectroscopy and mass spectrometry and contained tetrahydropyran, 1,3,5,7-tetra(methylene)heptane, and octahydrospiro[pyran-2,2'-pyrano[3,2-b]pyran] moieties. The absolute configuration of 1 was completely elucidated on the basis of ROESY correlations, J-based configuration analysis, and modified Mosher's ester analysis. Limaol showed moderate cytotoxicity when compared to OA against three cancer cell lines.
[Mh] Termos MeSH primário: Dinoflagelados/química
Toxinas Marinhas/química
Ácido Okadáico/química
Ácido Okadáico/isolamento & purificação
Policetídeos/isolamento & purificação
Policetídeos/farmacologia
Piranos/isolamento & purificação
Compostos de Espiro/isolamento & purificação
Compostos de Espiro/farmacologia
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Espectroscopia de Ressonância Magnética
Estrutura Molecular
Ácido Okadáico/farmacologia
Policetídeos/química
Piranos/química
Piranos/farmacologia
Compostos de Espiro/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Marine Toxins); 0 (Polyketides); 0 (Pyrans); 0 (Spiro Compounds); 0 (limaol); 1W21G5Q4N2 (Okadaic Acid); 4Q51CVY9O2 (dinophysistoxin 1)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170407
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jnatprod.7b00127


  8 / 3570 MEDLINE  
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[PMID]:28363841
[Au] Autor:Cakir M; Duzova H; Tekin S; Taslidere E; Kaya GB; Cigremis Y; Ozgocer T; Yologlu S
[Ad] Endereço:Department of Physiology, Faculty of Medicine, Inonu University, Malatya, Turkey. Electronic address: murat.cakir@bozok.edu.tr.
[Ti] Título:ACA, an inhibitor phospholipases A2 and transient receptor potential melastatin-2 channels, attenuates okadaic acid induced neurodegeneration in rats.
[So] Source:Life Sci;176:10-20, 2017 May 01.
[Is] ISSN:1879-0631
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:AIM: In recent studies, it has been shown that the Transient Receptor Potential Melastatin-2 Channels (TRPM2) and Phospholipases A2 (PLA ) inhibitors may have a protective effect on neurons. This study was aimed to investigate the protective effect of TRPM2 and PLA inhibitor N-(p-amylcinnamoyl) Anthranilic Acid (ACA) in a neurodegenerative model induced by Okadaic Acid (OKA). MAIN METHODS: OKA (200ng/10µl) was administered bilateral intracerebroventricularly as a single injection. KEY FINDINGS: OKA-treated rats showed significant impairments of spatial memory in Morris Water Maze Test. OKA-induced memory-impaired rats showed increased numbers of degenerated neurons and Caspase-3, tau phosphorylated ser396, ß-amyloid positive cells in the hippocampus and cerebral cortex. Furthermore, OKA-treated rats exhibited significantly increased MDA, TNF-α levels, and decreased SOD, GSH-PX enzyme activates and GSH levels of the tissues. ACA administration ameliorated OKA-induced memory impairment in rats. The ACA treatment also increased SOD and GSH-PX enzyme activation and GSH levels, and conversely decreased the levels of MDA, TNF-α. It was found that the numbers of the degenerated neurons and Caspase-3 positive cells of cortex and hippocampus regions were significantly reduced. SIGNIFICANCE: ACA administration attenuates the oxidative stress and neuroinflammation of OKA-induced neurodegeneration; and ameliorates the cognitive decline and neurodegeneration.
[Mh] Termos MeSH primário: Córtex Cerebral
Hipocampo
Doenças Neurodegenerativas
Ácido Okadáico/toxicidade
Inibidores de Fosfolipase A2/farmacologia
Canais de Cátion TRPM/metabolismo
ortoaminobenzoatos/farmacologia
[Mh] Termos MeSH secundário: Animais
Caspase 3/metabolismo
Córtex Cerebral/metabolismo
Córtex Cerebral/fisiopatologia
Hipocampo/metabolismo
Hipocampo/fisiopatologia
Masculino
Aprendizagem em Labirinto/efeitos dos fármacos
Memória/efeitos dos fármacos
Doenças Neurodegenerativas/induzido quimicamente
Doenças Neurodegenerativas/metabolismo
Doenças Neurodegenerativas/fisiopatologia
Doenças Neurodegenerativas/prevenção & controle
Fosfolipases A2/metabolismo
Ratos
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Phospholipase A2 Inhibitors); 0 (TRPM Cation Channels); 0 (ortho-Aminobenzoates); 1W21G5Q4N2 (Okadaic Acid); EC 3.1.1.4 (Phospholipases A2); EC 3.4.22.- (Casp3 protein, rat); EC 3.4.22.- (Caspase 3)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170428
[Lr] Data última revisão:
170428
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170402
[St] Status:MEDLINE


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[PMID]:28340282
[Au] Autor:Liu CY; Hsieh FS; Chu PY; Tsai WC; Huang CT; Yu YB; Huang TT; Ko PS; Hung MH; Wang WL; Shiau CW; Chen KF
[Ad] Endereço:Comprehensive Breast Health Centre, Taipei Veterans General Hospital, Taipei, Taiwan.
[Ti] Título:Carfilzomib induces leukaemia cell apoptosis via inhibiting ELK1/KIAA1524 (Elk-1/CIP2A) and activating PP2A not related to proteasome inhibition.
[So] Source:Br J Haematol;177(5):726-740, 2017 Jun.
[Is] ISSN:1365-2141
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Enhancing the tumour suppressive activity of protein phosphatase 2A (PP2A) has been suggested to be an anti-leukaemic strategy. KIAA1524 (also termed CIP2A), an oncoprotein inhibiting PP2A, is associated with disease progression in chronic myeloid leukaemia and may be prognostic in cytogenetically normal acute myeloid leukaemia. Here we demonstrated that the selective proteasome inhibitor, carfilzomib, induced apoptosis in sensitive primary leukaemia cells and in sensitive leukaemia cell lines, associated with KIAA1524 protein downregulation, increased PP2A activity and decreased p-Akt, but not with the proteasome inhibition effect of carfilzomib. Ectopic expression of KIAA1524, or pretreatment with the PP2A inhibitor, okadaic acid, suppressed carfilzomib-induced apoptosis and KIAA1524 downregulation in sensitive cells, whereas co-treatment with the PP2A agonist, forskolin, enhanced carfilzomib-induced apoptosis in resistant cells. Mechanistically, carfilzomib affected KIAA1524 transcription through disturbing ELK1 (Elk-1) binding to the KIAA1524 promoter. Moreover, the drug sensitivity and mechanism of carfilzomib in xenograft mouse models correlated well with the effects of carfilzomib on KIAA1524 and p-Akt expression, as well as PP2A activity. Our data disclosed a novel drug mechanism of carfilzomib in leukaemia cells and suggests the potential therapeutic implication of KIAA1524 in leukaemia treatment.
[Mh] Termos MeSH primário: Leucemia/tratamento farmacológico
Oligopeptídeos/farmacologia
[Mh] Termos MeSH secundário: Adulto
Idoso
Animais
Apoptose/efeitos dos fármacos
Autoantígenos/metabolismo
Linhagem Celular Tumoral
Cicloeximida/farmacologia
Regulação para Baixo/efeitos dos fármacos
Feminino
Células HL-60
Seres Humanos
Células K562
Leucemia/fisiopatologia
Masculino
Proteínas de Membrana/metabolismo
Camundongos Nus
Meia-Idade
Transplante de Neoplasias/métodos
Ácido Okadáico/farmacologia
Complexo de Endopeptidases do Proteassoma/metabolismo
Inibidores da Síntese de Proteínas/farmacologia
Células Tumorais Cultivadas
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Autoantigens); 0 (KIAA1524 protein, human); 0 (Membrane Proteins); 0 (Oligopeptides); 0 (Protein Synthesis Inhibitors); 1W21G5Q4N2 (Okadaic Acid); 72X6E3J5AR (carfilzomib); 98600C0908 (Cycloheximide); EC 3.4.25.1 (Proteasome Endopeptidase Complex)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170807
[Lr] Data última revisão:
170807
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170325
[St] Status:MEDLINE
[do] DOI:10.1111/bjh.14620


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[PMID]:28267764
[Au] Autor:Penberthy KK; Buckley MW; Arandjelovic S; Ravichandran K
[Ad] Endereço:Department of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, Virginia, United States of America.
[Ti] Título:Ex vivo modulation of the Foxo1 phosphorylation state does not lead to dysfunction of T regulatory cells.
[So] Source:PLoS One;12(3):e0173386, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Peripheral regulatory CD4+ T cells (Treg cells) prevent maladaptive inflammatory responses to innocuous foreign antigens. Treg cell dysfunction has been linked to many inflammatory diseases, including allergic airway inflammation. Glucocorticoids that are used to treat allergic airway inflammation and asthma are thought to work in part by promoting Treg cell differentiation; patients who are refractory to these drugs have defective induction of anti-inflammatory Treg cells. Previous observations suggest that Treg cells deficient in the transcription factor FoxO1 are pro-inflammatory, and that FoxO1 activity is regulated by its phosphorylation status and nuclear localization. Here, we asked whether altering the phosphorylation state of FoxO1 through modulation of a regulatory phosphatase might affect Treg cell function. In a mouse model of house dust mite-induced allergic airway inflammation, we observed robust recruitment of Treg cells to the lungs and lymph nodes of diseased mice, without an apparent increase in the Treg cytokine interleukin-10 in the airways. Intriguingly, expression of PP2A, a serine/threonine phosphatase linked to the regulation of FoxO1 phosphorylation, was decreased in the mediastinal lymph nodes of HDM-treated mice, mirroring the decreased PP2A expression seen in peripheral blood monocytes of glucocorticoid-resistant asthmatic patients. When we asked whether modulation of PP2A activity alters Treg cell function via treatment with the PP2A inhibitor okadaic acid, we observed increased phosphorylation of FoxO1 and decreased nuclear localization. However, dysregulation of FoxO1 did not impair Treg cell differentiation ex vivo or cause Treg cells to adopt a pro-inflammatory phenotype. Moreover, inhibition of PP2A activity did not affect the suppressive function of Treg cells ex vivo. Collectively, these data suggest that modulation of the phosphorylation state of FoxO1 via PP2A inhibition does not modify Treg cell function ex vivo. Our data also highlight the caveat in using ex vivo assays of Treg cell differentiation and function, in that while these assays are useful, they may not fully recapitulate Treg cell phenotypes that are observed in vivo.
[Mh] Termos MeSH primário: Hiper-Reatividade Brônquica/imunologia
Hiper-Reatividade Brônquica/metabolismo
Proteína Forkhead Box O1/metabolismo
Linfócitos T Reguladores/imunologia
Linfócitos T Reguladores/metabolismo
[Mh] Termos MeSH secundário: Alérgenos/imunologia
Animais
Diferenciação Celular/efeitos dos fármacos
Modelos Animais de Doenças
Expressão Gênica
Imunomodulação/efeitos dos fármacos
Interleucina-10/metabolismo
Contagem de Linfócitos
Camundongos
Ácido Okadáico/farmacologia
Fenótipo
Fosfoproteínas Fosfatases/genética
Fosfoproteínas Fosfatases/metabolismo
Fosforilação
Pyroglyphidae/imunologia
Linfócitos T Reguladores/citologia
Linfócitos T Reguladores/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Allergens); 0 (Forkhead Box Protein O1); 130068-27-8 (Interleukin-10); 1W21G5Q4N2 (Okadaic Acid); EC 3.1.3.16 (Phosphoprotein Phosphatases)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171108
[Lr] Data última revisão:
171108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170308
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0173386



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