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[PMID]:28748404
[Au] Autor:Scariot FJ; Jahn L; Delamare APL; Echeverrigaray S
[Ad] Endereço:Institute of Biotechnology, University of Caxias do Sul, Caxias do Sul, Rio Grande Do Sul, Brazil.
[Ti] Título:Necrotic and apoptotic cell death induced by Captan on Saccharomyces cerevisiae.
[So] Source:World J Microbiol Biotechnol;33(8):159, 2017 Aug.
[Is] ISSN:1573-0972
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Captan is one of the most widely used broad-spectrum fungicide applied to control several early and late diseases of grapes, apples, and other fruits and vegetables, and as other phthalimide fungicides is defined as a multisite compound with thiol-reactivity. Captan can affect non-target organisms as yeasts, modifying microbial populations and fermentation processes. In this study, we asked whether Captan thiol-reactivity and other mechanisms are involved in acute Captan-induced cell death on aerobic growing Saccharomyces cerevisiae. Thus for, we analyze cellular protein and non-protein thiols, cell membrane integrity, reactive oxygen species accumulation, phosphatidylserine externalization, and apoptotic mutants behavior. The results showed that when submitted to acute Captan treatment most cells lost their membrane integrity and died by necrosis due to Captan reaction with thiols. However, part of the cells, even maintaining their membrane integrity, lost their culture ability. These cells showed an apoptotic behavior that may be the result of non-protein thiol depletion and consequent increase of reactive oxygen species (ROS). ROS accumulation triggers a metacaspase-dependent apoptotic cascade, as shown by the higher viability of the yca1-deleted mutant. Together, necrosis and apoptosis are responsible for the high mortality detected after acute Captan treatment of aerobically growing cells of S. cerevisiae.
[Mh] Termos MeSH primário: Apoptose/efeitos dos fármacos
Captana/farmacologia
Morte Celular/efeitos dos fármacos
Saccharomyces cerevisiae/efeitos dos fármacos
[Mh] Termos MeSH secundário: Membrana Celular/efeitos dos fármacos
Fermentação
Fungicidas Industriais/farmacologia
Viabilidade Microbiana/efeitos dos fármacos
Mutação
Necrose
Espécies Reativas de Oxigênio/metabolismo
Saccharomyces cerevisiae/genética
Saccharomyces cerevisiae/crescimento & desenvolvimento
Proteínas de Saccharomyces cerevisiae/genética
Proteínas de Saccharomyces cerevisiae/metabolismo
Compostos de Sulfidrila/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fungicides, Industrial); 0 (Reactive Oxygen Species); 0 (Saccharomyces cerevisiae Proteins); 0 (Sulfhydryl Compounds); EOL5G26Q9F (Captan)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170728
[St] Status:MEDLINE
[do] DOI:10.1007/s11274-017-2325-3


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[PMID]:29289887
[Au] Autor:Moussa G; Alaaeddine R; Alaeddine LM; Nassra R; Belal ASF; Ismail A; El-Yazbi AF; Abdel-Ghany YS; Hazzaa A
[Ad] Endereço:Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt.
[Ti] Título:Novel click modifiable thioquinazolinones as anti-inflammatory agents: Design, synthesis, biological evaluation and docking study.
[So] Source:Eur J Med Chem;144:635-650, 2018 Jan 20.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Click chemistry was used to synthesize a new series of thioquinazolinone molecules equipped with propargyl moiety,1,2,3-triazolyl and isoxazolyl rings. Our design was based on merging pharmacophores previously reported to exhibit COX-2 inhibitory activities to a thioquinazolinone-privileged scaffold. The synthesized compounds were subjected to in vitro cyclooxygenase COX-1/COX-2 and 15-LOX inhibition assays. Compounds 2c, 3b, 3h, 3j, and 3k showed COX-2 inhibition with IC (µM) 0.18, 0.19, 0.11, 0.16 and 0.17 respectively. These values were compared to celecoxib (IC 0.05 µM), diclofenac (IC 0.8 µM) and indomethacin (IC 0.49 µM) reference drugs. They also showed 15-LOX inhibition with IC (µM) 6.21, 4.33, 7.62, 5.21 and 3.98 respectively. These values were compared with Zileuton (IC 2.41 µM) and Meclofenamate sodium (IC 5.64 µM) as positive controls. These compounds were further challenged by PMA-induced THP-1 differentiation assay where compounds 2c and 3j inhibited monocyte to macrophage differentiation efficiently with IC values of 4.78 µM and 5.63 µM, respectively, compared to that of diclofenac sodium (4.86 µM). On the other hand, 3h demonstrated a significantly increased potency compared to diclofenac in this assay (IC = 0.13 µM). The same compounds exhibited significant in vivo anti-inflammatory effect as indicated by the formalin-induced rat-paw edema test. Docking experiments of compounds 2c, 3b, 3h, 3j, and 3k into COX-2 binding pocket have been conducted, where strong binding interactions have been identified and effective overall docking scores have been recorded. Their drug-likeness has been assessed using Molinspiration, Molsoft and Pre-ADMET software products.
[Mh] Termos MeSH primário: Anti-Inflamatórios não Esteroides/farmacologia
Inibidores de Ciclo-Oxigenase/farmacologia
Desenho de Drogas
Inibidores de Lipoxigenase/farmacologia
Quinazolinonas/farmacologia
Compostos de Sulfidrila/farmacologia
[Mh] Termos MeSH secundário: Animais
Anti-Inflamatórios não Esteroides/síntese química
Anti-Inflamatórios não Esteroides/química
Araquidonato 15-Lipoxigenase/metabolismo
Diferenciação Celular/efeitos dos fármacos
Química Click
Ciclo-Oxigenase 1/metabolismo
Ciclo-Oxigenase 2/metabolismo
Inibidores de Ciclo-Oxigenase/síntese química
Inibidores de Ciclo-Oxigenase/química
Relação Dose-Resposta a Droga
Feminino
Seres Humanos
Inibidores de Lipoxigenase/síntese química
Inibidores de Lipoxigenase/química
Macrófagos/efeitos dos fármacos
Simulação de Acoplamento Molecular
Estrutura Molecular
Quinazolinonas/síntese química
Quinazolinonas/química
Ratos
Ratos Wistar
Relação Estrutura-Atividade
Compostos de Sulfidrila/síntese química
Compostos de Sulfidrila/química
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Cyclooxygenase Inhibitors); 0 (Lipoxygenase Inhibitors); 0 (Quinazolinones); 0 (Sulfhydryl Compounds); EC 1.13.11.33 (Arachidonate 15-Lipoxygenase); EC 1.14.99.1 (Cyclooxygenase 1); EC 1.14.99.1 (Cyclooxygenase 2); EC 1.14.99.1 (PTGS1 protein, human); EC 1.14.99.1 (PTGS2 protein, human)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180101
[St] Status:MEDLINE


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[PMID]:29478662
[Au] Autor:Luo P; Roca A; Tiede K; Privett K; Jiang J; Pinkstone J; Ma G; Veinot J; Boxall A
[Ad] Endereço:School of Environment Science and Spatial informatics, Chinese University of Mining and Technology, Xuzhou 221000, China. Electronic address: luoping@cumt.edu.cn.
[Ti] Título:Application of nanoparticle tracking analysis for characterising the fate of engineered nanoparticles in sediment-water systems.
[So] Source:J Environ Sci (China);64:62-71, 2018 Feb.
[Is] ISSN:1001-0742
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Novel applications of nanotechnology may lead to the release of engineered nanoparticles (ENPs), which result in concerns over their potential environmental hazardous impact. It is essential for the research workers to be able to quantitatively characterise ENPs in the environment and subsequently to assist the risk assessment of the ENPs. This study hence explored the application of nanoparticle tracking system (NTA) to quantitatively describe the behaviour of the ENPs in natural sediment-water systems. The NTA allows the measurement of both particle number concentration (PNC) and particle size distribution (PSD) of the ENPs. The developed NTA method was applied to a range of gold and magnetite ENPs with a selection of surface properties. The results showed that the positively-charged ENPs interacted more strongly with the sediment than neutral and negatively-charged ENPs. It was also found that the citrate coated Au ENPs had a higher distribution percentage (53%) than 11-mercaptoundecanoic acid coated Au ENPs (20%) and citrate coated magnetite ENPs (21%). The principles of the electrostatic interactions between hard (and soft) acids and bases (HSAB) are used to explain such behaviours; the hard base coating (i.e. citrate ions) will interact more strongly with hard acid (i.e. magnetite) than soft acid (i.e. gold). The results indicate that NTA is a complementary method to existing approaches to characterise the fate and behaviour of ENPs in natural sediment.
[Mh] Termos MeSH primário: Monitoramento Ambiental/métodos
Manufaturas
Nanopartículas/análise
Poluentes Químicos da Água/análise
[Mh] Termos MeSH secundário: Ácidos Graxos
Nanopartículas de Magnetita
Nanotecnologia
Eletricidade Estática
Compostos de Sulfidrila
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (11-mercaptoundecanoic acid); 0 (Fatty Acids); 0 (Magnetite Nanoparticles); 0 (Sulfhydryl Compounds); 0 (Water Pollutants, Chemical)
[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:180227
[St] Status:MEDLINE


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[PMID]:28746421
[Au] Autor:Sadowska-Bartosz I; Furmaniak P; Bieszczad-Bedrejczuk E; Bartosz G; Glowacki R
[Ad] Endereço:Department of Analytical Biochemistry, Faculty of Biology and Agriculture, University of Rzeszow, Rzeszów, Poland.
[Ti] Título:Developmental changes in the levels and redox potentials of main hemolymph thiols/disulfides in the Jamaican field cricket Gryllus assimilis.
[So] Source:Acta Biochim Pol;64(3):503-506, 2017.
[Is] ISSN:1734-154X
[Cp] País de publicação:Poland
[La] Idioma:eng
[Ab] Resumo:Main thiols and disulfides were determined in the hemolymph of the Jamaican field cricket Gryllus assimilis at various developmental stages. On the basis of these data, redox potentials of the glutathione, cysteine and homocysteine redox systems were calculated. The concentrations of all thiols studied decreased during development (at a stage of 6 molts) with respect to young crickets, and increased again in adult insects. Redox potentials of the glutathione and cysteine systems increased from values of -131.0±5.6 mV and -86.9±17.1 mV, respectively in young crickets to -58.0±3.6 mV and -36.1±4.2 mV, respectively, at the stage of 6 molts and decreased to values of -110.4±24.8 mV and -66.3±12.2 mV, respectively, in adult insects. Redox potentials of the glutathione and cysteine systems in the hemolymph of young and adult insects were similar to those reported for human plasma.
[Mh] Termos MeSH primário: Dissulfetos/metabolismo
Gryllidae/crescimento & desenvolvimento
Gryllidae/metabolismo
Hemolinfa/metabolismo
Compostos de Sulfidrila/metabolismo
[Mh] Termos MeSH secundário: Animais
Cisteína/metabolismo
Glutationa/metabolismo
Dissulfeto de Glutationa/metabolismo
Homocisteína/metabolismo
Ninfa/crescimento & desenvolvimento
Ninfa/metabolismo
Oxirredução
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Disulfides); 0 (Sulfhydryl Compounds); 0LVT1QZ0BA (Homocysteine); GAN16C9B8O (Glutathione); K848JZ4886 (Cysteine); ULW86O013H (Glutathione Disulfide)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170727
[St] Status:MEDLINE
[do] DOI:10.18388/abp.2017_1510


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[PMID]:28743765
[Au] Autor:Kurmanbayeva A; Bekturova A; Srivastava S; Soltabayeva A; Asatryan A; Ventura Y; Khan MS; Salazar O; Fedoroff N; Sagi M
[Ad] Endereço:Plant Stress Laboratory, French Associates Institute for Agriculture and Biotechnology of Drylands, Blaustein Institutes for Desert Research, Ben-Gurion University of the Negev, 84990, Israel.
[Ti] Título:Higher Novel L-Cys Degradation Activity Results in Lower Organic-S and Biomass in than the Related Saltwort, .
[So] Source:Plant Physiol;175(1):272-289, 2017 Sep.
[Is] ISSN:1532-2548
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:and are almost identical halophytes whose edible succulent shoots hold promise for commercial production in saline water. Enhanced sulfur nutrition may be beneficial to crops naturally grown on high sulfate. However, little is known about sulfate nutrition in halophytes. Here we show that (ecotype RN) exhibits a significant increase in biomass and organic-S accumulation in response to supplemental sulfate, whereas (ecotype VM) does not, instead exhibiting increased sulfate accumulation. We investigated the role of two pathways on organic-S and biomass accumulation in and : the sulfate reductive pathway that generates Cys and l-Cys desulfhydrase that degrades Cys to H S, NH , and pyruvate. The major function of -acetyl-Ser-(thiol) lyase (OAS-TL; EC 2.5.1.47) is the formation of l-Cys, but our study shows that the OAS-TL A and OAS-TL B of both halophytes are enzymes that also degrade l-Cys to H S. This activity was significantly higher in than in , especially upon sulfate supplementation. The activity of the sulfate reductive pathway key enzyme, adenosine 5'-phosphosulfate reductase (APR, EC 1.8.99.2), was significantly higher in than in These results suggest that the low organic-S level in is the result of high l-Cys degradation rate by OAS-TLs, whereas the greater organic-S and biomass accumulation in is the result of higher APR activity and low l-Cys degradation rate, resulting in higher net Cys biosynthesis. These results present an initial road map for halophyte growers to attain better growth rates and nutritional value of and .
[Mh] Termos MeSH primário: Amaranthaceae/metabolismo
Chenopodiaceae/metabolismo
Cisteína/metabolismo
Proteínas de Plantas/metabolismo
Salsola/metabolismo
Enxofre/metabolismo
[Mh] Termos MeSH secundário: Amaranthaceae/efeitos dos fármacos
Biomassa
Chenopodiaceae/efeitos dos fármacos
Cisteína Sintase/metabolismo
Oxirredutases atuantes sobre Doadores de Grupo Enxofre/metabolismo
Salinidade
Salsola/efeitos dos fármacos
Plantas Tolerantes a Sal
Sódio/farmacologia
Sulfatos/farmacologia
Compostos de Sulfidrila/metabolismo
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Plant Proteins); 0 (Sulfates); 0 (Sulfhydryl Compounds); 70FD1KFU70 (Sulfur); 9NEZ333N27 (Sodium); EC 1.8.- (Oxidoreductases Acting on Sulfur Group Donors); EC 1.8.99.2 (adenylylsulfate reductase); EC 2.5.1.47 (Cysteine Synthase); K848JZ4886 (Cysteine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170727
[St] Status:MEDLINE
[do] DOI:10.1104/pp.17.00780


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[PMID]:29311554
[Au] Autor:Frudd K; Burgoyne T; Burgoyne JR
[Ad] Endereço:King's College London, Cardiovascular Division, The British Heart Foundation, Centre of Excellence, The Rayne Institute, St Thomas' Hospital, London, SE1 7EH, UK.
[Ti] Título:Oxidation of Atg3 and Atg7 mediates inhibition of autophagy.
[So] Source:Nat Commun;9(1):95, 2018 01 08.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Macroautophagy (autophagy) is a crucial cellular stress response for degrading defective macromolecules and organelles, as well as providing bioenergetic intermediates during hypoxia and nutrient deprivation. Here we report a thiol-dependent process that may account for impaired autophagy during aging. This is through direct oxidation of key autophagy-related (Atg) proteins Atg3 and Atg7. When inactive Atg3 and Atg7 are protected from oxidation due to stable covalent interaction with their substrate LC3. This interaction becomes transient upon activation of Atg3 and Atg7 due to transfer of LC3 to phosphatidylethanolamine (lipidation), a process crucial for functional autophagy. However, loss in covalent-bound LC3 also sensitizes the catalytic thiols of Atg3 and Atg7 to inhibitory oxidation that prevents LC3 lipidation, observed in vitro and in mouse aorta. Here findings provide a thiol-dependent process for negatively regulating autophagy that may contribute to the process of aging, as well as therapeutic targets to regulate autophagosome maturation.
[Mh] Termos MeSH primário: Envelhecimento/metabolismo
Proteína 7 Relacionada à Autofagia/química
Proteínas Relacionadas à Autofagia/química
Autofagia/efeitos dos fármacos
Peróxido de Hidrogênio/farmacologia
Proteínas Associadas aos Microtúbulos/química
Enzimas de Conjugação de Ubiquitina/química
[Mh] Termos MeSH secundário: Animais
Aorta/citologia
Aorta/efeitos dos fármacos
Aorta/metabolismo
Autofagossomos/efeitos dos fármacos
Autofagossomos/metabolismo
Proteína 7 Relacionada à Autofagia/metabolismo
Proteínas Relacionadas à Autofagia/metabolismo
Células HEK293
Seres Humanos
Masculino
Camundongos Endogâmicos C57BL
Proteínas Associadas aos Microtúbulos/metabolismo
Miócitos de Músculo Liso/citologia
Miócitos de Músculo Liso/efeitos dos fármacos
Miócitos de Músculo Liso/metabolismo
Oxirredução
Fosfatidiletanolaminas/química
Fosfatidiletanolaminas/metabolismo
Cultura Primária de Células
Ratos
Compostos de Sulfidrila/química
Enzimas de Conjugação de Ubiquitina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Atg7 protein, mouse); 0 (Autophagy-Related Proteins); 0 (MAP1LC3 protein, mouse); 0 (Microtubule-Associated Proteins); 0 (Phosphatidylethanolamines); 0 (Sulfhydryl Compounds); 39382-08-6 (phosphatidylethanolamine); BBX060AN9V (Hydrogen Peroxide); EC 2.3.2.23 (Ubiquitin-Conjugating Enzymes); EC 6.2.1.45 (Autophagy-Related Protein 7); EC 6.3.2.- (Atg3 protein, mouse)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180110
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02352-z


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[PMID]:29223921
[Au] Autor:Zhou B; Ye J; Yang N; Chen L; Zhuo Z; Mao L; Liu Q; Lan G; Ning J; Ge G; Yang L; Shen Y; Wang S; Zhang W
[Ad] Endereço:School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China.
[Ti] Título:Metabolism and pharmacokinetics of alantolactone and isoalantolactone in rats: Thiol conjugation as a potential metabolic pathway.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1072:370-378, 2018 Jan 01.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Alantolactone (AL) and isoalantolactone (IAL), two major active sesquiterpene lactones isolated from Radix Inulae extract, have a wide range of pharmacological activities. The predominant metabolic pathway of AL and IAL observed was glutathione (GSH) conjugation in vitro, which could occur in the absence of metabolic enzymes. Non-enzymatic conjugation with cysteine (Cys) couldalso be observed. Four metabolites (AL-GSH, AL-Cys, IAL-GSH, IAL-Cys) were subsequently isolated and confirmed by nuclear magnetic resonance (NMR). The results indicated that the thiol of GSH or Cys can be reacted with the exomethylene carbon atoms of α, ß-unsaturated carbonyl of AL and IAL. After intravenous administration in rats, AL and IAL were extensively metabolized, and the exposure, as measured by area under the concentration-time curve (AUC), for AL-GSH, AL-Cys, IAL-GSH, and IAL-Cys was approximately 1.54-, 0.96-, 1.50-, and 0.91-fold that of the parent drug, respectively. The AUC ratio of metabolites to parent compounds of oral administration was 3.66-, 9.19-, 12.97-, and 9.92-fold that of the parent drug for the above metabolites, respectively. The bioavailability of AL-total (AL, AL-GSH, AL-Cys) and IAL-total (IAL, IAL-GSH, IAL-Cys) was, respectively, 8.39% and 13.07%, which was 3.62- and 6.95- fold that of AL (2.32%) and IAL (1.88%), respectively. The oral exposure will be underestimated if the parent drugs are tested alone. These findings provide useful information for preclinical safety evaluation, and for predicting AL and IAL metabolism in humans.
[Mh] Termos MeSH primário: Lactonas
Sesquiterpenos de Eudesmano
Sesquiterpenos
Compostos de Sulfidrila/metabolismo
[Mh] Termos MeSH secundário: Animais
Cromatografia Líquida
Cisteína/metabolismo
Glutationa/metabolismo
Seres Humanos
Lactonas/análise
Lactonas/química
Lactonas/metabolismo
Lactonas/farmacocinética
Masculino
Microssomos Hepáticos/metabolismo
Ratos
Ratos Sprague-Dawley
Sesquiterpenos/análise
Sesquiterpenos/química
Sesquiterpenos/metabolismo
Sesquiterpenos/farmacocinética
Sesquiterpenos de Eudesmano/análise
Sesquiterpenos de Eudesmano/química
Sesquiterpenos de Eudesmano/metabolismo
Sesquiterpenos de Eudesmano/farmacocinética
Espectrometria de Massas em Tandem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Lactones); 0 (Sesquiterpenes); 0 (Sesquiterpenes, Eudesmane); 0 (Sulfhydryl Compounds); BYH07P620U (isoalantolactone); GAN16C9B8O (Glutathione); K848JZ4886 (Cysteine); M7GSN5Q1M6 (alantolactone)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171211
[St] Status:MEDLINE


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[PMID]:29203246
[Au] Autor:Popielarski M; Ponamarczuk H; Stasiak M; Michalec L; Bednarek R; Studzian M; Pulaski L; Swiatkowska M
[Ad] Endereço:Department of Cytobiology and Proteomics, Medical University of Lodz, 6/8 Mazowiecka St., 92-215 Lodz, Poland. Electronic address: marcin.popielarski@umed.lodz.pl.
[Ti] Título:The role of Protein Disulfide Isomerase and thiol bonds modifications in activation of integrin subunit alpha11.
[So] Source:Biochem Biophys Res Commun;495(2):1635-1641, 2018 01 08.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Integrins belong to a family of transmembrane receptors that mediate cell migration and adhesion to ECM. Extracellular domains of integrin heterodimers contain cysteine-rich regions, which are potential sites of thiol-disulfide exchanges. Rearrangements of extracellular disulfide bonds regulate activation of integrin receptors by promoting transition from an inactive state into a ligand-binding competent state. Modifications of integrin disulfide bonds dependent on oxidation-reduction can be mediated by Protein Disulfide Isomerse (PDI). This paper provides evidences that binding to integrin ligands initiate changes in free thiol pattern on cell surface and that thiol-disulfide exchange mediated by PDI leads to activation of integrin subunit α11. By employing co-immunoprecipitation and confocal microscopy analysis we showed that α11ß1 and PDI create complexes bounded by disulfide bonds. Using surface plasmon resonance we provide biochemical evidence that PDI can interact directly with integrin subunit α11.
[Mh] Termos MeSH primário: Cadeias alfa de Integrinas/química
Cadeias alfa de Integrinas/metabolismo
Isomerases de Dissulfetos de Proteínas/metabolismo
[Mh] Termos MeSH secundário: Adesão Celular
Movimento Celular
Células Cultivadas
Seres Humanos
Imunoprecipitação
Integrina beta1/química
Integrina beta1/metabolismo
Microscopia Confocal
Domínios e Motivos de Interação entre Proteínas
Compostos de Sulfidrila/química
Compostos de Sulfidrila/metabolismo
Ressonância de Plasmônio de Superfície
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (ITGA11 protein, human); 0 (Integrin alpha Chains); 0 (Integrin beta1); 0 (Sulfhydryl Compounds); EC 5.3.4.1 (Protein Disulfide-Isomerases)
[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:171206
[St] Status:MEDLINE


  9 / 27122 MEDLINE  
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[PMID]:29378097
[Au] Autor:Shumakova; Shipelin VA; Sidorova YS; Trushina EN; Mustafina OK; Pridvorova SM; Gmoshinsky IV; Khotimchenko SA
[Ti] Título:[Toxicological evaluation of nanosized colloidal silver, stabilized with polyvinylpyrrolidone. I. Characterization of nanomaterial, integral, hematological parameters, level of thiol compounds and liver cell apoptosis].
[So] Source:Vopr Pitan;84(6):46-57, 2015.
[Is] ISSN:0042-8833
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Ab] Resumo:Nano-sized colloidal silver (NCS) is currently one of the most widely used nanomaterials in medicine and consumer's products. Nanoparticles (NPs) of silver, in addition to the direct exposition through products may expose human via various environmental objects. The aim of the study is to assess the safe doses of silver NP received orally. The investigated NCS contained silver NPs with diameter of 10­60 nm, predominantly with a nearly spherical form stabilized with polyvinylpyrrolidone (PVP). The experiment was performed during 92 days in 5 groups of male Wistar rats (n=15 in each group), receiving a balanced semisynthetic diet. Animal of group 1 (control) received vehicle (deionized water) intragastrically for 30 days and then with food, groups from 2nd to 4th ­ PVP and groups from 3rd to 5th NCS, in doses respectively, 0.1; 1.0 and 10 mg/kg body weight (b.w.) in terms of silver. The dose of PVP in groups from 2nd to 5th did not differ, amounting to 200 mg/kg b.w. During the experiment, the weight gain, skin condition, activity, stool, cognitive function were assessed. At the end of the feeding period weight of internal organs, intestinal wall permeability to protein macromolecules, liver thiols, standard values of blood erythrocytes, leukocytes and platelets, hepatocyte apoptosis by flow cytometry were studied. These results suggest that in terms of weight gain, lung relative mass, average erythrocyte volume, hemoglobin content and concentration in erythrocytes, the relative proportion of lymphocytes and neutrophils adverse changes have been observed at a dose of 10 mg NPs per kg of b.w. At lower levels of exposure (0.1 and 1.0 mg/kg b.w.) some specific changes were also observed (in terms of thiols pool in liver, cognitive function, relative abundance of monocytes, the number of dead hepatocytes), which, however, did not possess an unambiguous dependence on the dose. Possible mechanisms of the toxic action of the NCS have been discussed.
[Mh] Termos MeSH primário: Apoptose/efeitos dos fármacos
Hepatócitos/metabolismo
Fígado/metabolismo
Nanopartículas Metálicas/toxicidade
Povidona/análogos & derivados
Prata/toxicidade
Compostos de Sulfidrila/metabolismo
[Mh] Termos MeSH secundário: Animais
Coloides
Hepatócitos/patologia
Fígado/patologia
Masculino
Nanopartículas Metálicas/química
Povidona/química
Povidona/toxicidade
Ratos
Ratos Wistar
Prata/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Colloids); 0 (Sulfhydryl Compounds); 25249-54-1 (polyvinylpolypyrrolidone); 3M4G523W1G (Silver); FZ989GH94E (Povidone)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180130
[St] Status:MEDLINE


  10 / 27122 MEDLINE  
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Texto completo SciELO Brasil
[PMID]:29236925
[Au] Autor:Magalhães LS; Bomfim LG; Mota SG; Cruz GS; Corrêa CB; Tanajura DM; Lipscomb MW; Borges VM; Jesus AR; Almeida RP; Moura TR
[Ad] Endereço:Laboratório de Biologia Molecular, Hospital Universitário, Universidade Federal de Sergipe, Aracaju, SE, Brasil.
[Ti] Título:Increased thiol levels in antimony-resistant Leishmania infantum isolated from treatment-refractory visceral leishmaniasis in Brazil.
[So] Source:Mem Inst Oswaldo Cruz;113(2):119-125, 2018 Feb.
[Is] ISSN:1678-8060
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:BACKGROUND Treatment-refractory visceral leishmaniasis (VL) has become an important problem in many countries. OBJECTIVES We evaluated the antimony-resistance mechanisms of Leishmania infantum isolated from VL patients refractory or responsive to treatment with pentavalent antimony. METHODS Strains isolated from antimony-refractory patients (in vitro antimony-resistant isolates) and antimony-responsive patients (in vitro antimony-sensitive isolates) were examined. Morphological changes were evaluated by transmission electron microscopy after trivalent antimony exposure. P-glycoprotein (P-gp) efflux pump activity was evaluated using the pump-specific inhibitor verapamil hydrochloride, and the role of thiol in trivalent antimony resistance was investigated using the enzymatic inhibitor L-buthionine sulfoximine. FINDINGS Antimony treatment induced fewer alterations in the cellular structure of L. infantum resistant isolates than in that of sensitive isolates. P-gp efflux activity was not involved in antimony resistance in these isolates. Importantly, the resistant isolates contained higher levels of thiol compared to the sensitive isolates, and inhibition of thiol synthesis in the resistant isolates recovered their sensitivity to trivalent antimony treatment, and enhanced the production of reactive oxygen species in promastigotes exposed to the drug. MAIN CONCLUSIONS Our results demonstrate that isolates from patients with antimony-refractory VL exhibited higher thiol levels than antimony-sensitive isolates. This indicates that redox metabolism plays an important role in the antimony-resistance of New World VL isolates.
[Mh] Termos MeSH primário: Antimônio/farmacologia
Leishmania infantum/efeitos dos fármacos
Leishmania infantum/ultraestrutura
Leishmaniose Visceral/parasitologia
Compostos de Sulfidrila/metabolismo
[Mh] Termos MeSH secundário: Butionina Sulfoximina/farmacologia
Resistência a Medicamentos
Inibidores Enzimáticos/farmacologia
Seres Humanos
Microscopia Eletrônica de Transmissão
Testes de Sensibilidade Parasitária
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (Sulfhydryl Compounds); 5072-26-4 (Buthionine Sulfoximine); 9IT35J3UV3 (Antimony)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171214
[St] Status:MEDLINE



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