Base de dados : MEDLINE
Pesquisa : D08.811.277.352.100.680.750.937 [Categoria DeCS]
Referências encontradas : 9623 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 963 ir para página                         

  1 / 9623 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29391000
[Au] Autor:Khan MF; Nahar N; Rashid RB; Chowdhury A; Rashid MA
[Ad] Endereço:Department of Pharmacy, State University of Bangladesh, Dhaka, 1205, Bangladesh.
[Ti] Título:Computational investigations of physicochemical, pharmacokinetic, toxicological properties and molecular docking of betulinic acid, a constituent of Corypha taliera (Roxb.) with Phospholipase A2 (PLA2).
[So] Source:BMC Complement Altern Med;18(1):48, 2018 Feb 02.
[Is] ISSN:1472-6882
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Betulinic acid (BA) is a natural triterpenoid compound and exhibits a wide range of biological and medicinal properties including anti-inflammatory activity. Therefore, this theoretical investigation is performed to evaluate (a) physicochemical properties such as acid dissociation constant (pKa), distribution coefficient (logD), partition coefficient (logP), aqueous solubility (logS), solvation free energy, dipole moment, polarizability, hyperpolarizability and different reactivity descriptors, (b) pharmacokinetic properties like human intestinal absorption (HIA), cellular permeability, skin permeability (P ), plasma protein binding (PPB), penetration of the blood brain barrier (BBB), (c) toxicological properties including mutagenicity, carcinogenicity, risk of inhibition of hERG gene and (d) molecular mechanism of anti-inflammatory action which will aid the development of analytical method and the synthesis of BA derivatives. METHODS: The physicochemical properties were calculated using MarvinSketch 15.6.29 and Gaussian 09 software package. The pharmacokinetic and toxicological properties were calculated on online server PreADMET. Further, the molecular docking study was conducted on AutoDock vina in PyRx 0.8. RESULTS: The aqueous solubility increased with increasing pH due to the ionization of BA leading to decrease in distribution coefficient. The solvation energies in water, dimethyl sulfoxide (DMSO), acetonitrile, n-octanol, chloroform and carbon tetrachloride were - 41.74 kJ/mol, - 53.80 kJ/mol, - 66.27 kJ/mol, - 69.64 kJ/mol, - 65.96 kJ/mol and - 60.13 kJ/mol, respectively. From the results of polarizability and softness, it was clear that BA is less stable and hence, kinetically more reactive in water. BA demonstrated good human intestinal absorption (HIA) and moderate cellular permeability. Further, BA also exhibited positive CNS activity due to high permeability through BBB. The toxicological study revealed that BA was a mutagenic compound but noncarcinogenic in mice model. Moreover, molecular docking study of BA with PLA2 revealed that BA interacts with GLY22 & GLY29 through hydrogen bond formation and LEU2, PHE5, HIS6, ALA17, ALA18, HIS47 and TYR51 through different types of hydrophobic interactions. The binding affinity of BA was - 41.00 kJ/mol which is comparable to the binding affinity of potent inhibitor 6-Phenyl-4(R)-(7-Phenyl-heptanoylamino)-hexanoic acid (BR4) (- 33.89 kJ/mol). CONCLUSIONS: Our computed properties may assist the development of analytical method to assay BA or to develop BA derivatives with better pharmacokinetic and toxicological profile.
[Mh] Termos MeSH primário: Fosfolipases A2/química
Fosfolipases A2/metabolismo
Triterpenos/química
Triterpenos/metabolismo
[Mh] Termos MeSH secundário: Fenômenos Químicos
Concentração de Íons de Hidrogênio
Simulação de Acoplamento Molecular
Fosfolipases A2/análise
Ligação Proteica
Termodinâmica
Triterpenos/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Triterpenes); 4G6A18707N (betulinic acid); EC 3.1.1.4 (Phospholipases A2)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180203
[St] Status:MEDLINE
[do] DOI:10.1186/s12906-018-2116-x


  2 / 9623 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29197624
[Au] Autor:Fernández ML; Quartino PY; Arce-Bejarano R; Fernández J; Camacho LF; Gutiérrez JM; Kuemmel D; Fidelio G; Lomonte B
[Ad] Endereço:Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica San José 11501, Costa Rica.
[Ti] Título:Intravascular hemolysis induced by phospholipases A from the venom of the Eastern coral snake, Micrurus fulvius: Functional profiles of hemolytic and non-hemolytic isoforms.
[So] Source:Toxicol Lett;286:39-47, 2018 Apr.
[Is] ISSN:1879-3169
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:A unique feature of the venom of Micrurus fulvius (Eastern coral snake) is its ability to induce severe intravascular hemolysis in particular species, such as dogs or mice. This effect was previously shown to be induced by distinct phospholipase A (PLA ) isoforms which cause direct hemolysis in vitro, an uncommon finding for such enzymes. The functional profiles of PLA -17, a direct hemolytic enzyme, and PLA -12, a co-existing venom isoform lacking such effect, were compared. The enzymes differed not only in their ability to cause intravascular hemolysis: PLA -17 additionally displayed lethal, myotoxic, and anticoagulant actions, whereas PLA -12 lacked these effects. PLA -12 was much more active in hydrolyzing a monodisperse synthetic substrate than PLA -17, but the catalytic activity of latter was notably higher on a micellar substrate, or towards pure phospholipid artificial monolayers under controlled lateral pressures. Interestingly, PLA -17 could hydrolyze substrate at a pressure of 20 mN m , in contrast to PLA -12 or the non-toxic pancreatic PLA . This suggests important differences in the monolayer penetrating power, which could be related to differences in toxicity. Comparative examination of primary structures and predicted three-dimensional folding of PLA -12 and PLA -17, revealed that differences concentrate in their N-terminal and central regions, leading to variations of the surface properties at the membrane interacting interface. PLA -17 presents a less basic interfacial surface than PLA -12, but more bulky aromatic residues, which could be associated to its higher membrane-penetrating strength. Altogether, these structural and functional comparative observations suggest that the ability of PLA s to penetrate substrate interfaces could be a major determinant of toxicity, perhaps more important than protein surface charge.
[Mh] Termos MeSH primário: Cobras Corais
Venenos Elapídicos/toxicidade
Hemólise/efeitos dos fármacos
Fosfolipases A2/toxicidade
Proteínas de Répteis/toxicidade
[Mh] Termos MeSH secundário: Animais
Relação Dose-Resposta a Droga
Venenos Elapídicos/enzimologia
Feminino
Masculino
Camundongos
Modelos Moleculares
Permeabilidade
Fosfolipases A2/química
Fosfolipases A2/metabolismo
Conformação Proteica
Dobramento de Proteína
Isoformas de Proteínas
Proteínas de Répteis/química
Proteínas de Répteis/metabolismo
Relação Estrutura-Atividade
Propriedades de Superfície
Fatores de Tempo
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Elapid Venoms); 0 (Protein Isoforms); 0 (Reptilian Proteins); 0 (micrurus venom); EC 3.1.1.4 (Phospholipases A2)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171204
[St] Status:MEDLINE


  3 / 9623 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29292090
[Au] Autor:Miyake M; Ito Y; Suzuki H; Tomizawa M; Sato H; Liu M; Okamura A; Nakajima T; Ohtani K; Takino H; Inagaki H; Kamijima M
[Ad] Endereço:Department of Occupational and Environmental Health, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
[Ti] Título:Epididymal phospholipidosis is a possible mechanism for spermatotoxicity induced by the organophosphorus insecticide fenitrothion in rats.
[So] Source:Toxicol Lett;285:27-33, 2018 Mar 15.
[Is] ISSN:1879-3169
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Fenitrothion (FNT) is used worldwide in agricultural and public health settings. Spermatogenesis is a toxicological target of FNT under high-dose exposure. Although anti-androgenic action is postulated to be the mechanism associated with this toxicity, few studies have examined histopathology of androgen-dependent male accessory sex organs. The present study aimed to reveal the effects of FNT on the accessory organs of rats exhibiting spermatotoxicity in the absence of testicular histopathological changes. Furthermore, a possible novel molecular target was clarified. Male Wistar rats were orally administered 5 or 10 mg/kg FNT or its major metabolite 3-methyl-4-nitrophenol (MNP), or vehicle only, 4 days per week for 9 weeks. Then the epididymis, prostate, and seminal vesicles were collected. FNT and MNP did not show anti-androgenic effects but FNT induced cytoplasmic vacuolation in the epithelial cells of epididymal ducts and hyperplasia of mucosal folds/epithelial papillomatosis in seminal vesicles. FNT and MNP induced epididymal phospholipidosis, which was presumably caused by inhibition of epididymal secreted phospholipase A2 (sPLA2). Percentages of morphologically normal sperm and immature sperm were significantly predicted from both epididymal sPLA2 and phospholipid levels and from epididymal sPLA2, respectively. These results suggest that epididymal phospholipidosis plays an important role in FNT-induced spermatotoxicity. Anti-androgenic actions were not observed.
[Mh] Termos MeSH primário: Epididimo/efeitos dos fármacos
Fenitrotion/toxicidade
Inseticidas/toxicidade
Fosfolipídeos/metabolismo
Espermatogênese/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Relação Dose-Resposta a Droga
Epididimo/metabolismo
Epididimo/patologia
Masculino
Fosfolipases A2/metabolismo
Ratos Wistar
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Insecticides); 0 (Phospholipids); EC 3.1.1.4 (Phospholipases A2); W8M4X3Y7ZY (Fenitrothion)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180219
[Lr] Data última revisão:
180219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180103
[St] Status:MEDLINE


  4 / 9623 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28743267
[Au] Autor:Valdez-Cruz NA; Reynoso-Cereceda GI; Pérez-Rodriguez S; Restrepo-Pineda S; González-Santana J; Olvera A; Zavala G; Alagón A; Trujillo-Roldán MA
[Ad] Endereço:Programa de Investigación de Producción de Biomoléculas, Unidad de Bioprocesos, Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, AP. 70228, CP 04510, Mexico City, Mexico. adrivaldez1@gmail.com.
[Ti] Título:Production of a recombinant phospholipase A2 in Escherichia coli using resonant acoustic mixing that improves oxygen transfer in shake flasks.
[So] Source:Microb Cell Fact;16(1):129, 2017 Jul 25.
[Is] ISSN:1475-2859
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Shake flasks are widely used during the development of bioprocesses for recombinant proteins. Cultures of recombinant Escherichia coli with orbital mixing (OM) have an oxygen limitation negatively affecting biomass growth and recombinant-protein production. With the aim to improve mixing and aeration in shake flask cultures, we analyzed cultures subjected to OM and the novel resonant acoustic mixing (RAM) by applying acoustic energy to E. coli BL21-Gold (DE3): a producer of recombinant phospholipase A2 (rPLA2) from Micrurus laticollaris snake venom. RESULTS: Comparing OM with RAM (200 rpm vs. 7.5g) at the same initial volumetric oxygen transfer coefficient (k a ≈ 80 h ) ~69% less biomass was obtained with OM compared with RAM. We analyzed two more conditions increasing agitation until maximal speed (12.5 and 20g), and ~1.6- and ~1.4-fold greater biomass was obtained as compared with cultures at 7.5g. Moreover, the specific growth rate was statistically similar in all cultures carried out in RAM, but ~1.5-fold higher than that in cultures carried out under OM. Almost half of the glucose was consumed in OM, whereas between 80 and 100% of the glucose was consumed in RAM cultures, doubling biomass per glucose yields. Differential organic acid production was observed, but acetate production was prevented at the maximal RAM (20g). The amount of rPLA2 in both, OM and RAM cultures, represented 38 ± 5% of the insoluble protein. A smaller proportion of α-helices and ß-sheet of purified inclusion bodies (IBs) were appreciated by ATR-FTIR from cultures carried out under OM, than those from RAM. At maximal agitation by RAM, internal E. coli localization patterns of protein aggregation changed, as well as, IBs proteolytic degradation, in conjunction with the formation of small external vesicles, although these changes did not significantly affect the cell survival response. CONCLUSIONS: In moderate-cell-density recombinant E. coli BL21-Gold (DE3) cultures, the agitation increases in RAM (up to the maximum) was not enough to avoid the classical oxygen limitation that happens in OM shake flasks. However, RAM presents a decrease of oxygen limitation, resulting in a favorable effect on biomass growth and volumetric rPLA2 production. While under OM a higher recombinant protein yield was obtained.
[Mh] Termos MeSH primário: Escherichia coli/metabolismo
Oxigênio/metabolismo
Fosfolipases A2/metabolismo
[Mh] Termos MeSH secundário: Técnicas de Cultura Celular por Lotes
Escherichia coli/crescimento & desenvolvimento
Glucose/metabolismo
Corpos de Inclusão/genética
Corpos de Inclusão/metabolismo
Cinética
Microscopia Eletrônica de Transmissão
Fosfolipases A2/genética
Proteínas Recombinantes/biossíntese
Proteínas Recombinantes/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Recombinant Proteins); EC 3.1.1.4 (Phospholipases A2); IY9XDZ35W2 (Glucose); S88TT14065 (Oxygen)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180205
[Lr] Data última revisão:
180205
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170727
[St] Status:MEDLINE
[do] DOI:10.1186/s12934-017-0746-1


  5 / 9623 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27777178
[Au] Autor:Pla D; Sanz L; Sasa M; Acevedo ME; Dwyer Q; Durban J; Pérez A; Rodriguez Y; Lomonte B; Calvete JJ
[Ad] Endereço:Structural and Functional Venomics Laboratory, Instituto de Biomedicina de Valencia, CSIC, Valencia, Spain.
[Ti] Título:Proteomic analysis of venom variability and ontogeny across the arboreal palm-pitvipers (genus Bothriechis).
[So] Source:J Proteomics;152:1-12, 2017 01 30.
[Is] ISSN:1876-7737
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Bothriechis is a genus of eleven currently recognized slender and arboreal venomous snakes, commonly called palm-pitvipers that range from southern Mexico to northern South America. Despite dietary studies suggesting that palm-pitvipers are generalists with an ontogenetic shift toward endothermic prey, venom proteomic analyses have revealed remarkable divergence between the venoms of the Costa Rican species, B. lateralis, B. schlegelii, B. supraciliaris, and B. nigroviridis. To achieve a more complete picture of the venomic landscape across Bothriechis, the venom proteomes of biodiversity of the northern Middle American highland palm-pitvipers, B. thalassinus, B. aurifer, and B. bicolor from Guatemala, B. marchi from Honduras, and neonate Costa Rican B. lateralis and B. schlegelii, were investigated. B. thalassinus and B. aurifer venoms are comprised by similar toxin arsenals dominated by SVMPs (33-39% of the venom proteome), CTLs (11-16%), BPP-like molecules (10-13%), and CRISPs (5-10%), and are characterized by the absence of PLA proteins. Conversely, the predominant (35%) components of B. bicolor are D49-PLA molecules. The venom proteome of B. marchi is similar to B. aurifer and B. thalassinus in that it is rich in SVMPs and BPPs, but also contains appreciable amounts (14.3%) of PLA s. The major toxin family found in the venoms of both neonate B. lateralis and B. schlegelii, is serine proteinase (SVSP), comprising about 20% of their toxin arsenals. The venom of neonate B. schlegelii is the only palm-pitviper venom where relative high amounts of Kunitz-type (6.3%) and γPLA (5.2%) inhibitors have been identified. Despite notable differences between their proteomes, neonate venoms are more similar to each other than to adults of their respective species. However, the ontogenetic changes taking place in the venom of B. lateralis strongly differ from those that occur in the venom of B. schlegelii. Thus, the ontogenetic change in B. lateralis produces a SVMP-rich venom, whereas in B. schlegelii the age-dependent compositional shift generates a PLA -rich venom. Overall, genus-wide venomics illustrate the high evolvability of palm-pitviper venoms. The integration of the pattern of venom variation across Bothriechis into a phylogenetic and biogeographic framework may lay the foundation for assessing, in future studies, the evolutionary path that led to the present-day variability of the venoms of palm-pitvipers. SIGNIFICANCE: Bothriechis represents a monophyletic basal genus of eleven arboreal palm-pitvipers that range from southern Mexico to northern South America. Despite palm-pitvipers' putative status as diet generalists, previous proteomic analyses have revealed remarkable divergence between the venoms of Costa Rican species, B. lateralis, B. schlegelii, B. supraciliaris, and B. nigroviridis. Our current proteomic study of Guatemalan species, B. thalassinus, B. aurifer, and B. bicolor, Honduran B. marchi, and neonate B. lateralis and B. schlegelii from Costa Rica was undertaken to deepen our understanding of the evolutionary pattern of venom proteome diversity across Bothriechis. Ancestral characters are often, but not always, preserved in an organism's development. Venoms of neonate B. lateralis and B. schlegelii are more similar to each other than to adults of their respective species, suggesting that the high evolvability of palm-pitviper venoms may represent an inherent feature of Bothriechis common ancestor. Our genus-wide data identified four nodes of venom phenotype differentiation across the phylogeny of Bothriechis. Integrated into a phylogenetic and biogeographic framework, the pattern of venom variation across Bothriechis may lay the groundwork to establish whether divergence was driven by selection for efficient resource exploitation in arboreal 'islands', thereby contributing to the ecological speciation of the genus.
[Mh] Termos MeSH primário: Biodiversidade
Venenos de Crotalídeos/química
Proteoma/análise
[Mh] Termos MeSH secundário: Fatores Etários
Animais
Evolução Biológica
Venenos de Crotalídeos/enzimologia
Fosfolipases A2/análise
Filogenia
Proteômica/métodos
Serina Proteases/análise
Toxinas Biológicas/análise
Viperidae
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Crotalid Venoms); 0 (Proteome); 0 (Toxins, Biological); EC 3.1.1.4 (Phospholipases A2); EC 3.4.- (Serine Proteases)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180118
[Lr] Data última revisão:
180118
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161107
[St] Status:MEDLINE


  6 / 9623 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29023569
[Au] Autor:Vulfius CA; Kasheverov IE; Kryukova EV; Spirova EN; Shelukhina IV; Starkov VG; Andreeva TV; Faure G; Zouridakis M; Tsetlin VI; Utkin YN
[Ad] Endereço:Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region, Russia.
[Ti] Título:Pancreatic and snake venom presynaptically active phospholipases A2 inhibit nicotinic acetylcholine receptors.
[So] Source:PLoS One;12(10):e0186206, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Phospholipases A2 (PLA2s) are enzymes found throughout the animal kingdom. They hydrolyze phospholipids in the sn-2 position producing lysophospholipids and unsaturated fatty acids, agents that can damage membranes. PLA2s from snake venoms have numerous toxic effects, not all of which can be explained by phospholipid hydrolysis, and each enzyme has a specific effect. We have earlier demonstrated the capability of several snake venom PLA2s with different enzymatic, cytotoxic, anticoagulant and antiproliferative properties, to decrease acetylcholine-induced currents in Lymnaea stagnalis neurons, and to compete with α-bungarotoxin for binding to nicotinic acetylcholine receptors (nAChRs) and acetylcholine binding protein. Since nAChRs are implicated in postsynaptic and presynaptic activities, in this work we probe those PLA2s known to have strong presynaptic effects, namely ß-bungarotoxin from Bungarus multicinctus and crotoxin from Crotalus durissus terrificus. We also wished to explore whether mammalian PLA2s interact with nAChRs, and have examined non-toxic PLA2 from porcine pancreas. It was found that porcine pancreatic PLA2 and presynaptic ß-bungarotoxin blocked currents mediated by nAChRs in Lymnaea neurons with IC50s of 2.5 and 4.8 µM, respectively. Crotoxin competed with radioactive α-bungarotoxin for binding to Torpedo and human α7 nAChRs and to the acetylcholine binding protein. Pancreatic PLA2 interacted similarly with these targets; moreover, it inhibited radioactive α-bungarotoxin binding to the water-soluble extracellular domain of human α9 nAChR, and blocked acetylcholine induced currents in human α9α10 nAChRs heterologously expressed in Xenopus oocytes. These and our earlier results show that all snake PLA2s, including presynaptically active crotoxin and ß-bungarotoxin, as well as mammalian pancreatic PLA2, interact with nAChRs. The data obtained suggest that this interaction may be a general property of all PLA2s, which should be proved by further experiments.
[Mh] Termos MeSH primário: Neurônios/fisiologia
Pâncreas/enzimologia
Fosfolipases A2/farmacologia
Venenos de Serpentes/enzimologia
[Mh] Termos MeSH secundário: Acetilcolina/metabolismo
Animais
Bungarotoxinas/farmacologia
Crotoxina/farmacologia
Seres Humanos
Lymnaea/citologia
Neurônios/efeitos dos fármacos
Receptores Nicotínicos/metabolismo
Suínos/metabolismo
Xenopus laevis/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bungarotoxins); 0 (Receptors, Nicotinic); 0 (Snake Venoms); 9007-40-3 (Crotoxin); EC 3.1.1.4 (Phospholipases A2); N9YNS0M02X (Acetylcholine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171013
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0186206


  7 / 9623 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28892824
[Au] Autor:Lippestad M; Hodges RR; Utheim TP; Serhan CN; Dartt DA
[Ad] Endereço:Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States.
[Ti] Título:Resolvin D1 Increases Mucin Secretion in Cultured Rat Conjunctival Goblet Cells via Multiple Signaling Pathways.
[So] Source:Invest Ophthalmol Vis Sci;58(11):4530-4544, 2017 Sep 01.
[Is] ISSN:1552-5783
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Purpose: Goblet cells in the conjunctiva secrete mucin into the tear film protecting the ocular surface. The proresolution mediator resolvin D1 (RvD1) regulates mucin secretion to maintain homeostasis during physiological conditions and in addition, actively terminates inflammation. We determined the signaling mechanisms used by RvD1 in cultured rat conjunctival goblet cells to increase intracellular [Ca2+] ([Ca2+]i) and induce glycoconjugate secretion. Methods: Increase in [Ca2+]i were measured using fura 2/AM and glycoconjugate secretion determined using an enzyme-linked lectin assay with the lectin Ulex Europaeus Agglutinin 1. Signaling pathways activated by RvD1 were studied after goblet cells were pretreated with signaling pathway inhibitors before stimulation with RvD1. The results were compared with results when goblet cells were stimulated with RvD1 alone and percent inhibition calculated. Results: The increase in [Ca2+]i stimulated by RvD1 was blocked by inhibitors to phospholipases (PL-) -D, -C, -A2, protein kinase C (PKC), extracellular signal-regulated kinases (ERK)1/2 and Ca2+/calmodulin-dependent kinase (Ca2+/CamK). Glycoconjugate secretion was significantly inhibited by PLD, -C, -A2, ERK1/2 and Ca2+/CamK, but not PKC. Conclusions: We conclude that RvD1 increases glycoconjugate secretion from goblet cells via multiple signaling pathways including PLC, PLD, and PLA2, as well as their signaling components ERK1/2 and Ca2+/CamK to preserve the mucous layer and maintain homeostasis by protecting the eye from desiccating stress, allergens, and pathogens.
[Mh] Termos MeSH primário: Túnica Conjuntiva/efeitos dos fármacos
Ácidos Docosa-Hexaenoicos/farmacologia
Células Caliciformes/efeitos dos fármacos
Mucinas/secreção
Transdução de Sinais/fisiologia
[Mh] Termos MeSH secundário: Animais
Cálcio/metabolismo
Células Cultivadas
Túnica Conjuntiva/metabolismo
Ensaio de Imunoadsorção Enzimática
Fura-2/análogos & derivados
Fura-2/metabolismo
Células Caliciformes/metabolismo
Receptores de Inositol 1,4,5-Trifosfato/metabolismo
Sistema de Sinalização das MAP Quinases/fisiologia
Masculino
Fosfolipase D/metabolismo
Fosfolipases A2/metabolismo
Ratos
Ratos Sprague-Dawley
Receptores de Lipoxinas/metabolismo
Fosfolipases Tipo C/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Inositol 1,4,5-Trisphosphate Receptors); 0 (Mucins); 0 (Receptors, Lipoxin); 0 (lipoxin A(4) receptor, rat); 0 (resolvin D1); 105344-37-4 (fura-2-am); 25167-62-8 (Docosahexaenoic Acids); EC 3.1.1.4 (Phospholipases A2); EC 3.1.4.- (Type C Phospholipases); EC 3.1.4.4 (Phospholipase D); SY7Q814VUP (Calcium); TSN3DL106G (Fura-2)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170929
[Lr] Data última revisão:
170929
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170912
[St] Status:MEDLINE
[do] DOI:10.1167/iovs.17-21914


  8 / 9623 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28867438
[Au] Autor:Cavalcante WLG; Noronha-Matos JB; Timóteo MA; Fontes MRM; Gallacci M; Correia-de-Sá P
[Ad] Endereço:Departamento de Farmacologia, Instituto de Ciências Biológicas, UFMG, Av. Antônio Carlos, 6627 Belo Horizonte, Brazil; Laboratório de Farmacologia e Neurobiologia, Instituto de Ciências Biomédicas Abel Salazar - Universidade do Porto (ICBAS-UP), R. Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portug
[Ti] Título:Neuromuscular paralysis by the basic phospholipase A subunit of crotoxin from Crotalus durissus terrificus snake venom needs its acid chaperone to concurrently inhibit acetylcholine release and produce muscle blockage.
[So] Source:Toxicol Appl Pharmacol;334:8-17, 2017 Nov 01.
[Is] ISSN:1096-0333
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND AND PURPOSE: Crotoxin (CTX), a heterodimeric phospholipase A (PLA ) neurotoxin from Crotalus durissus terrificus snake venom, promotes irreversible blockade of neuromuscular transmission. Indirect electrophysiological evidence suggests that CTX exerts a primary inhibitory action on transmitter exocytosis, yet contribution of a postsynaptic action of the toxin resulting from nicotinic receptor desensitization cannot be excluded. Here, we examined the blocking effect of CTX on nerve-evoked transmitter release measured directly using radioisotope neurochemistry and video microscopy with the FM4-64 fluorescent dye. EXPERIMENTAL APPROACH: Experiments were conducted using mice phrenic-diaphragm preparations. Real-time fluorescence video microscopy and liquid scintillation spectrometry techniques were used to detect transmitter exocytosis and nerve-evoked [ H]-acetylcholine ([ H]ACh) release, respectively. Nerve-evoked myographic recordings were also carried out for comparison purposes. KEY RESULTS: Both CTX (5µg/mL) and its basic PLA subunit (CB, 20µg/mL) had biphasic effects on nerve-evoked transmitter exocytosis characterized by a transient initial facilitation followed by a sustained decay. CTX and CB reduced nerve-evoked [ H]ACh release by 60% and 69%, respectively, but only the heterodimer, CTX, decreased the amplitude of nerve-evoked muscle twitches. CONCLUSION AND IMPLICATIONS: Data show that CTX exerts a presynaptic inhibitory action on ACh release that is highly dependent on its intrinsic PLA activity. Given the high safety margin of the neuromuscular transmission, one may argue that the presynaptic block caused by the toxin is not enough to produce muscle paralysis unless a concurrent postsynaptic inhibitory action is also exerted by the CTX heterodimer.
[Mh] Termos MeSH primário: Acetilcolina/antagonistas & inibidores
Venenos de Crotalídeos/toxicidade
Crotalus/fisiologia
Crotoxina/toxicidade
Chaperonas Moleculares/metabolismo
Bloqueio Neuromuscular
[Mh] Termos MeSH secundário: Acetilcolina/metabolismo
Animais
Venenos de Crotalídeos/química
Crotoxina/química
Feminino
Masculino
Camundongos
Chaperonas Moleculares/química
Músculos/efeitos dos fármacos
Neurotoxinas/toxicidade
Fosfolipases A2
Subunidades Proteicas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Crotalid Venoms); 0 (Molecular Chaperones); 0 (Neurotoxins); 0 (Protein Subunits); 9007-40-3 (Crotoxin); EC 3.1.1.4 (Phospholipases A2); N9YNS0M02X (Acetylcholine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170905
[St] Status:MEDLINE


  9 / 9623 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28855258
[Au] Autor:Jang KK; Lee ZW; Kim B; Jung YH; Han HJ; Kim MH; Kim BS; Choi SH
[Ad] Endereço:From the National Research Laboratory of Molecular Microbiology and Toxicology, Department of Agricultural Biotechnology, Center for Food Safety and Toxicology, and.
[Ti] Título:Identification and characterization of encoding a phospholipase A essential for pathogenesis.
[So] Source:J Biol Chem;292(41):17129-17143, 2017 Oct 13.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The marine bacterium causes food-borne diseases, which may lead to life-threatening septicemia in some individuals. Therefore, identifying virulence factors in is of high priority. We performed a transcriptome analysis on after infection of human intestinal HT29-methotrexate cells and found induction of , encoding a putative phospholipase, PlpA. Bioinformatics, biochemical, and genetic analyses demonstrated that PlpA is a phospholipase A secreted in a type II secretion system-dependent manner. Compared with the wild type, the mutant exhibited reduced mortality, systemic infection, and inflammation in mice as well as low cytotoxicity toward the human epithelial INT-407 cells. Moreover, mutation attenuated the release of actin and cytosolic cyclophilin A from INT-407 cells, indicating that PlpA is a virulence factor essential for causing lysis and necrotic death of the epithelial cells. transcription was growth phase-dependent, reaching maximum levels during the early stationary phase. Also, transcription factor HlyU and cAMP receptor protein (CRP) mediate additive activation and host-dependent induction of Molecular biological analyses revealed that expression is controlled via the promoter, P , and that HlyU and CRP directly bind to P upstream sequences. Taken together, this study demonstrated that PlpA is a type II secretion system-dependent secretory phospholipase A regulated by HlyU and CRP and is essential for the pathogenicity of .
[Mh] Termos MeSH primário: Proteínas de Bactérias/metabolismo
Fosfolipases A2/metabolismo
Vibrioses/enzimologia
Vibrio vulnificus/enzimologia
Vibrio vulnificus/patogenicidade
[Mh] Termos MeSH secundário: Proteínas de Bactérias/genética
Sistemas de Secreção Bacterianos/genética
Sistemas de Secreção Bacterianos/metabolismo
Linhagem Celular
Seres Humanos
Mucosa Intestinal/microbiologia
Mucosa Intestinal/patologia
Fosfolipases A2/genética
Fatores de Transcrição/genética
Fatores de Transcrição/metabolismo
Vibrioses/genética
Vibrioses/patologia
Vibrio vulnificus/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Bacterial Secretion Systems); 0 (Transcription Factors); EC 3.1.1.4 (Phospholipases A2)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170901
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.791657


  10 / 9623 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28796890
[Au] Autor:Uyama T; Tsuboi K; Ueda N
[Ad] Endereço:Department of Biochemistry, Kagawa University School of Medicine, Japan.
[Ti] Título:An involvement of phospholipase A/acyltransferase family proteins in peroxisome regulation and plasmalogen metabolism.
[So] Source:FEBS Lett;591(18):2745-2760, 2017 Sep.
[Is] ISSN:1873-3468
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The H-Ras-like suppressor (HRASLS) is a protein family consisting of five members in humans. Despite their discovery as tumor suppressors, we demonstrated that all these proteins are phospholipid-metabolizing enzymes, such as phospholipase (PL) A /A and acyltransferase. We thus proposed to rename HRASLS1-5 as PLA/acyltransferase (PLAAT)-1-5. Notably, PLAATs exhibit N-acyltransferase activity to biosynthesize N-acylated ethanolamine phospholipids, including N-acyl-plasmalogen, which serve as precursors of bioactive N-acylethanolamines. Furthermore, the overexpression of PLAAT-3 in animal cells causes disappearance of peroxisomes and a remarkable reduction in plasmalogen levels. This finding might be related to the inhibitory effect of PLAAT-3 on the chaperone activity of the peroxin PEX19. In this article, we will review our recent findings about PLAAT proteins, with special reference to their roles in peroxisome biogenesis and plasmalogen metabolism.
[Mh] Termos MeSH primário: Peroxissomos/metabolismo
Plasmalogênios/metabolismo
[Mh] Termos MeSH secundário: Animais
Diacilglicerol O-Aciltransferase/metabolismo
Etanolaminas/metabolismo
Seres Humanos
Proteínas de Membrana/metabolismo
Fosfolipases A1/metabolismo
Fosfolipases A2/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Ethanolamines); 0 (Membrane Proteins); 0 (N-acylethanolamines); 0 (Plasmalogens); EC 2.3.1.20 (Diacylglycerol O-Acyltransferase); EC 3.1.1.32 (Phospholipases A1); EC 3.1.1.4 (Phospholipases A2)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171011
[Lr] Data última revisão:
171011
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170811
[St] Status:MEDLINE
[do] DOI:10.1002/1873-3468.12787



página 1 de 963 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde