Base de dados : MEDLINE
Pesquisa : D02.675 [Categoria DeCS]
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  1 / 1904 MEDLINE  
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[PMID]:29210387
[Au] Autor:Deplazes E; Poger D; Cornell B; Cranfield CG
[Ad] Endereço:School of Biomedical Sciences, Curtin Health Innovation Research Institute and Curtin Institute for Computation, Curtin University, Perth, WA 6845, Australia. evelyne.deplazes@curtin.edu.au.
[Ti] Título:The effect of hydronium ions on the structure of phospholipid membranes.
[So] Source:Phys Chem Chem Phys;20(1):357-366, 2017 Dec 20.
[Is] ISSN:1463-9084
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:This work seeks to identify the mechanisms by which hydronium ions (H O ) modulate the structure of phospholipid bilayers by studying the interactions of H O with phospholipids at the molecular level. For this, we carried out multiple microsecond-long unrestrained molecular dynamics (MD) simulations of a POPC bilayer at different H O concentrations. The results show that H O accumulates at the membrane surface where it displaces water and forms strong and long-lived hydrogen bonds with the phosphate and carbonyl oxygens in phospholipids. This results in a concentration-dependent reduction of the area per lipid and an increase in bilayer thickness. This study provides an important molecular-level insight into the mechanism of how H O modulates the structure of biological membranes and is a critical step towards a better understanding of the effect of low pH on mammalian and bacterial membranes.
[Mh] Termos MeSH primário: Bicamadas Lipídicas/química
Oniocompostos/química
Fosfolipídeos/química
[Mh] Termos MeSH secundário: Ligações de Hidrogênio
Simulação de Dinâmica Molecular
Fosfatidilcolinas/química
Água/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Lipid Bilayers); 0 (Onium Compounds); 0 (Phosphatidylcholines); 0 (Phospholipids); 059QF0KO0R (Water); 5046UKT60S (hydronium ion); TE895536Y5 (1-palmitoyl-2-oleoylphosphatidylcholine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171207
[St] Status:MEDLINE
[do] DOI:10.1039/c7cp06776c


  2 / 1904 MEDLINE  
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[PMID]:28885019
[Au] Autor:Quadri M; Stokes C; Gulsevin A; Felts ACJ; Abboud KA; Papke RL; Horenstein NA
[Ad] Endereço:Department of Chemistry, University of Florida , P.O. Box 117200, Gainesville, Florida 32611-7200, United States.
[Ti] Título:Sulfonium as a Surrogate for Ammonium: A New α7 Nicotinic Acetylcholine Receptor Partial Agonist with Desensitizing Activity.
[So] Source:J Med Chem;60(18):7928-7934, 2017 Sep 28.
[Is] ISSN:1520-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Weak partial agonists that promote a desensitized state of the α7 nicotinic acetylcholine receptor (nAChR) have been associated with anti-inflammatory effects. Exemplar compounds feature a tertiary or quaternary ammonium group. We report the synthesis, structure, and electrophysiological evaluation of 1-ethyl-4-phenylthiomorpholin-1-ium triflate, a weak partial agonist with a sulfonium isostere of the ammonium pharmacophore. These results offer new insights in understanding nAChR-ligand interactions and provide a new chemical space to target the α7 nAChR.
[Mh] Termos MeSH primário: Morfolinas/química
Morfolinas/farmacologia
Agonistas Nicotínicos/química
Agonistas Nicotínicos/farmacologia
Oniocompostos/química
Oniocompostos/farmacologia
Compostos de Sulfônio/química
Compostos de Sulfônio/farmacologia
Receptor Nicotínico de Acetilcolina alfa7/agonistas
[Mh] Termos MeSH secundário: Compostos de Amônio/síntese química
Compostos de Amônio/química
Compostos de Amônio/farmacologia
Animais
Seres Humanos
Modelos Moleculares
Morfolinas/síntese química
Agonistas Nicotínicos/síntese química
Oniocompostos/síntese química
Compostos de Sulfônio/síntese química
Xenopus laevis
Receptor Nicotínico de Acetilcolina alfa7/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (1-ethyl-4-phenylthiomorpholin-1-ium); 0 (Ammonium Compounds); 0 (Morpholines); 0 (Nicotinic Agonists); 0 (Onium Compounds); 0 (Sulfonium Compounds); 0 (alpha7 Nicotinic Acetylcholine Receptor)
[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:170909
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jmedchem.7b00875


  3 / 1904 MEDLINE  
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[PMID]:28750088
[Au] Autor:Foti A; Dorendorf F; Leimkühler S
[Ad] Endereço:Department of Molecular Enzymology, Institute of Biochemistry and Biology, University of Potsdam, Potsdam, Germany.
[Ti] Título:A single nucleotide polymorphism causes enhanced radical oxygen species production by human aldehyde oxidase.
[So] Source:PLoS One;12(7):e0182061, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Aldehyde oxidases (AOXs) are molybdo-flavoenzymes characterized by broad substrate specificity, oxidizing aromatic/aliphatic aldehydes into the corresponding carboxylic acids and hydroxylating various heteroaromatic rings. The enzymes use oxygen as the terminal electron acceptor and produce reduced oxygen species during turnover. The physiological function of mammalian AOX isoenzymes is still unclear, however, human AOX (hAOX1) is an emerging enzyme in phase-I drug metabolism. Indeed, the number of xenobiotics acting as hAOX1 substrates is increasing. Further, numerous single-nucleotide polymorphisms (SNPs) have been identified within the hAOX1 gene. SNPs are a major source of inter-individual variability in the human population, and SNP-based amino acid exchanges in hAOX1 reportedly modulate the catalytic function of the enzyme in either a positive or negative fashion. In this report we selected ten novel SNPs resulting in amino acid exchanges in proximity to the FAD site of hAOX1 and characterized the purified enzymes after heterologous expression in Escherichia coli. The hAOX1 variants were characterized carefully by quantitative differences in their ability to produce superoxide radical. ROS represent prominent key molecules in physiological and pathological conditions in the cell. Our data reveal significant alterations in superoxide anion production among the variants. In particular the SNP-based amino acid exchange L438V in proximity to the isoalloxanzine ring of the FAD cofactor resulted in increased rate of superoxide radical production of 75%. Considering the high toxicity of the superoxide in the cell, the hAOX1-L438V SNP variant is an eventual candidate for critical or pathological roles of this natural variant within the human population.
[Mh] Termos MeSH primário: Aldeído Oxidase/genética
Polimorfismo de Nucleotídeo Único/genética
Espécies Reativas de Oxigênio/metabolismo
[Mh] Termos MeSH secundário: Aldeído Oxidase/química
Aldeído Oxidase/isolamento & purificação
Aminoácidos/genética
Anaerobiose
Domínio Catalítico
Coenzimas/metabolismo
Transporte de Elétrons
Flavina-Adenina Dinucleotídeo/metabolismo
Seres Humanos
Ferro/metabolismo
Cinética
Modelos Moleculares
Molibdênio/metabolismo
Proteínas Mutantes/isolamento & purificação
NAD/metabolismo
Oniocompostos/metabolismo
Multimerização Proteica
Espectrofotometria Ultravioleta
Superóxidos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acids); 0 (Coenzymes); 0 (Mutant Proteins); 0 (Onium Compounds); 0 (Reactive Oxygen Species); 0U46U6E8UK (NAD); 11062-77-4 (Superoxides); 146-14-5 (Flavin-Adenine Dinucleotide); 6HJ411TU98 (diphenyleneiodonium); 81AH48963U (Molybdenum); E1UOL152H7 (Iron); EC 1.2.3.1 (AOX1 protein, human); EC 1.2.3.1 (Aldehyde Oxidase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171004
[Lr] Data última revisão:
171004
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170728
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0182061


  4 / 1904 MEDLINE  
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[PMID]:28709950
[Au] Autor:Lu J; Risbood P; Kane CT; Hossain MT; Anderson L; Hill K; Monks A; Wu Y; Antony S; Juhasz A; Liu H; Jiang G; Harris E; Roy K; Meitzler JL; Konaté M; Doroshow JH
[Ad] Endereço:Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
[Ti] Título:Characterization of potent and selective iodonium-class inhibitors of NADPH oxidases.
[So] Source:Biochem Pharmacol;143:25-38, 2017 Nov 01.
[Is] ISSN:1873-2968
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The NADPH oxidases (NOXs) play a recognized role in the development and progression of inflammation-associated disorders, as well as cancer. To date, several NOX inhibitors have been developed, through either high throughput screening or targeted disruption of NOX interaction partners, although only a few have reached clinical trials. To improve the efficacy and bioavailability of the iodonium class NOX inhibitor diphenylene iodonium (DPI), we synthesized 36 analogs of DPI, focusing on improved solubility and functionalization. The inhibitory activity of the analogs was interrogated through cell viability and clonogenic studies with a colon cancer cell line (HT-29) that depends on NOX for its proliferative potential. Lack of altered cellular respiration at relevant iodonium analog concentrations was also demonstrated. Additionally, inhibition of ROS generation was evaluated with a luminescence assay for superoxide, or by Amplex Red® assay for H O production, in cell models expressing specific NOX isoforms. DPI and four analogs (NSCs 740104, 751140, 734428, 737392) strongly inhibited HT-29 cell growth and ROS production with nanomolar potency in a concentration-dependent manner. NSC 737392 and 734428, which both feature nitro functional groups at the meta position, had >10-fold higher activity against ROS production by cells that overexpress dual oxidase 2 (DUOX2) than the other compounds examined (IC ≈200-400nM). Based on these results, we synthesized and tested NSC 780521 with optimized potency against DUOX2. Iodonium analogs with anticancer activity, including the first generation of targeted agents with improved specificity against DUOX2, may provide a novel therapeutic approach to NOX-driven tumors.
[Mh] Termos MeSH primário: Proliferação Celular/efeitos dos fármacos
Inibidores Enzimáticos/farmacologia
NADH NADPH Oxirredutases/antagonistas & inibidores
Oniocompostos/farmacologia
Tiofenos/farmacologia
[Mh] Termos MeSH secundário: Sobrevivência Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Oxidases Duais
Inibidores Enzimáticos/síntese química
Inibidores Enzimáticos/química
Células HT29
Seres Humanos
Estrutura Molecular
NADH NADPH Oxirredutases/genética
NADPH Oxidases/antagonistas & inibidores
NADPH Oxidases/genética
Oniocompostos/síntese química
Oniocompostos/química
Consumo de Oxigênio/efeitos dos fármacos
Espécies Reativas de Oxigênio/antagonistas & inibidores
Tiofenos/síntese química
Tiofenos/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (Onium Compounds); 0 (Reactive Oxygen Species); 0 (Thiophenes); 45955-43-9 (iodonium thiophene); 6HJ411TU98 (diphenyleneiodonium); EC 1.11.1.- (Dual Oxidases); EC 1.6.- (NADH, NADPH Oxidoreductases); EC 1.6.3.- (NADPH Oxidases); EC 1.6.3.1 (DUOX2 protein, human)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170716
[St] Status:MEDLINE


  5 / 1904 MEDLINE  
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[PMID]:28682956
[Au] Autor:Ji ZH; Liu ZJ; Liu ZT; Zhao W; Williams BA; Zhang HF; Li L; Xu SY
[Ad] Endereço:From the *Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China; and †Department of Anesthesiology, University of Pittsburgh, Pittsburgh, Pennsylvania.
[Ti] Título:Diphenyleneiodonium Mitigates Bupivacaine-Induced Sciatic Nerve Damage in a Diabetic Neuropathy Rat Model by Attenuating Oxidative Stress.
[So] Source:Anesth Analg;125(2):653-661, 2017 Aug.
[Is] ISSN:1526-7598
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Increased oxidative stress has been linked to local anesthetic-induced nerve injury in a diabetic neuropathy (DN) rat model. The current study explores the effects of diphenyleneiodonium (DPI) chloride, an NADPH oxidase (NOX) inhibitor, on bupivacaine-induced sciatic nerve injury in DN rats. METHODS: A rat DN model was established through high-fat diet feeding and streptozotocin injection. The model was confirmed via testing (i) blood glucose, (ii) hindpaw allodynia responses to von Frey (VF) monofilaments, (iii) paw withdrawal thermal latency (PWTL), and (iv) nerve conduction velocity (NCV). Bupivacaine (Bup, 0.2 mL, 5 mg/mL) was used to block the right sciatic nerve. DPI (1 mg/kg) was injected subcutaneously 24 hours and 30 minutes before the sciatic block. At 24 hours after the block, NCV, various reactive oxygen species, and Caspase-3 were evaluated to determine the extent of sciatic nerve injury. RESULTS: The DN rat model was successfully established. Compared with the DN control group, the postblock values of VF responses (DN-Con, 16.5 ± 1.3 g; DN + Bup, 19.1 ± 1.5 g, P < .001) and PWTL significantly increased (DN-Con, 13.3 ± 1.1 seconds; DN + Bup, 14.6 ± 1.1 seconds, P = .028); the NCV of sciatic nerve was significantly reduced (DN-Con, 38.8 ± 2.4 m/s, DN + Bup, 30.5 ± 2.0 m/s, P = .003), and sciatic nerve injury (as indicated by axonal area) was more severe in the bupivacaine-treated DN group (DN-Con, 11.6 ± 0.3 µm, DN + Bup, 7.5 ± 0.3 µm, P < .001). In addition, DPI treatment significantly improved nerve function (VF responses, 17.3 ± 1.3 g; PWTL, 13.4 ± 1.1 seconds; NCV, 35.6 ± 3.1 m/s) and mitigated loss of axonal area (9.6 ± 0.3 µm). Compared to the DN + Bup group (without DPI), the levels of lipid peroxides and hydroperoxides, as well as the protein expression of NOX2, NOX4, and Caspase-3, were significantly reduced in the DN + Bup + DPI group (P < .05). CONCLUSIONS: Subcutaneous injection of DPI appears to protect against the functional and neurohistological damage of bupivacaine-blocked sciatic nerves in a high-fat diet/streptozotocin-induced DN model.
[Mh] Termos MeSH primário: Anestésicos Locais/administração & dosagem
Anestésicos Locais/efeitos adversos
Bupivacaína/efeitos adversos
Neuropatias Diabéticas/fisiopatologia
Estresse Oxidativo/efeitos dos fármacos
Nervo Isquiático/lesões
[Mh] Termos MeSH secundário: Animais
Eletrofisiologia
Inibidores Enzimáticos/uso terapêutico
Hiperalgesia/fisiopatologia
Peróxidos Lipídicos/química
Masculino
Bloqueio Nervoso
Oniocompostos/uso terapêutico
Traumatismos dos Nervos Periféricos/induzido quimicamente
Ratos
Ratos Sprague-Dawley
Neuropatia Ciática/fisiopatologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anesthetics, Local); 0 (Enzyme Inhibitors); 0 (Lipid Peroxides); 0 (Onium Compounds); 6HJ411TU98 (diphenyleneiodonium); Y8335394RO (Bupivacaine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170814
[Lr] Data última revisão:
170814
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170707
[St] Status:MEDLINE
[do] DOI:10.1213/ANE.0000000000002186


  6 / 1904 MEDLINE  
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[PMID]:28579328
[Au] Autor:Chen S; Zhang Y; Li X; Jia H; Lu J
[Ad] Endereço:Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, PR China.
[Ti] Título:The evaluations of Tc cyclopentadienyl tricarbonyl triphenyl phosphonium cation for multidrug resistance.
[So] Source:Bioorg Med Chem Lett;27(15):3551-3554, 2017 08 01.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A triphenylphosphonium cation, [ Tc]Technetium cyclopentadienyltricarbonyl-6-hexanoyl-triphenylphosphonium cation ([ Tc]3) was prepared to target multidrug resistance (MDR). The radiotracer was evaluated in the MDR-negative MCF-7 and MDR-positive MCF-7/ADR cell lines in vitro, as well as animal models in vivo. [ Tc]3 was proofed to be a substrate of P-glycoprotein and multidrug resistant protein 1, and showed a higher accumulation in the MDR-negative MCF-7 cells compared to Tc-sestamibi in vitro. The MCF-7 tumor-to-MCF-7/ADR tumor ratio of [ Tc]3 was ∼3 at 1hp.i. in the biodistribution study. These results demonstrated the capability of the radiotracer to detect multidrug resistance in tumor cells.
[Mh] Termos MeSH primário: Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo
Neoplasias da Mama/diagnóstico por imagem
Resistência a Múltiplos Medicamentos
Resistência a Medicamentos Antineoplásicos
Oniocompostos/metabolismo
Compostos de Organotecnécio/metabolismo
Compostos Radiofarmacêuticos/metabolismo
Tomografia Computadorizada de Emissão de Fóton Único/métodos
[Mh] Termos MeSH secundário: Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo
Animais
Mama/diagnóstico por imagem
Mama/efeitos dos fármacos
Mama/metabolismo
Neoplasias da Mama/tratamento farmacológico
Neoplasias da Mama/metabolismo
Feminino
Seres Humanos
Células MCF-7
Camundongos Endogâmicos BALB C
Camundongos Nus
Oniocompostos/análise
Oniocompostos/farmacocinética
Compostos de Organotecnécio/análise
Compostos de Organotecnécio/farmacocinética
Compostos Radiofarmacêuticos/análise
Compostos Radiofarmacêuticos/farmacocinética
Especificidade por Substrato
Distribuição Tecidual
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (ATP Binding Cassette Transporter, Sub-Family B); 0 (ATP-Binding Cassette, Sub-Family B, Member 1); 0 (Onium Compounds); 0 (Organotechnetium Compounds); 0 (Radiopharmaceuticals); 0 (technetium 99m cyclopentadienyltricarbonyl-6-hexanoyltriphenylphosphonium)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171125
[Lr] Data última revisão:
171125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170606
[St] Status:MEDLINE


  7 / 1904 MEDLINE  
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[PMID]:28530834
[Au] Autor:Wang L; Cheng R; Fujinaga M; Yang J; Zhang Y; Hatori A; Kumata K; Yang J; Vasdev N; Du Y; Ran C; Zhang MR; Liang SH
[Ad] Endereço:Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital & Harvard Medical School , Boston, Massachusetts 02114, United States.
[Ti] Título:A Facile Radiolabeling of [ F]FDPA via Spirocyclic Iodonium Ylides: Preliminary PET Imaging Studies in Preclinical Models of Neuroinflammation.
[So] Source:J Med Chem;60(12):5222-5227, 2017 Jun 22.
[Is] ISSN:1520-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A suitable TSPO PET ligand may visualize and quantify neuroinflammation in a living brain. Herein we report a F-ligand, [ F]2 ([ F]FDPA), is radiolabeled in high yield and high specific activity based on our spirocyclic iodonium ylide (SCIDY) strategy. [ F]2 demonstrated saturable specific binding to TSPO, substantially elevated brain uptake, and slow washout of bound PET signal in the preclinical models of brain neuroinflammation (cerebral ischemia and Alzheimer's disease).
[Mh] Termos MeSH primário: Proteínas de Transporte/metabolismo
Encefalite/diagnóstico por imagem
Radioisótopos de Flúor/química
Marcação por Isótopo/métodos
Tomografia por Emissão de Pósitrons/métodos
Receptores de GABA-A/metabolismo
[Mh] Termos MeSH secundário: Animais
Autorradiografia
Encéfalo/diagnóstico por imagem
Encéfalo/patologia
Técnicas de Química Sintética
Meios de Contraste
Modelos Animais de Doenças
Radioisótopos de Flúor/farmacocinética
Camundongos Transgênicos
Oniocompostos/química
Pirazóis/química
Pirimidinas/química
Ratos Sprague-Dawley
Distribuição Tecidual
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carrier Proteins); 0 (Contrast Media); 0 (Fluorine Radioisotopes); 0 (N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo(1,5-a)pyrimidin-3-yl)acetamide); 0 (Onium Compounds); 0 (Pyrazoles); 0 (Pyrimidines); 0 (Receptors, GABA-A); 141440-82-6 (Tspo protein, rat)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170523
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jmedchem.7b00432


  8 / 1904 MEDLINE  
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[PMID]:28446427
[Au] Autor:Zaidman NA; O'Grady KE; Patil N; Milavetz F; Maniak PJ; Kita H; O'Grady SM
[Ad] Endereço:Department of Integrative Biology and Physiology University of Minnesota, Minneapolis, Minnesota.
[Ti] Título:Airway epithelial anion secretion and barrier function following exposure to fungal aeroallergens: role of oxidative stress.
[So] Source:Am J Physiol Cell Physiol;313(1):C68-C79, 2017 Jul 01.
[Is] ISSN:1522-1563
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Aeroallergens produced by can elicit life-threatening exacerbations of asthma in patients sensitized to this fungus. In this study, the effect of on ion transport mechanisms underlying mucociliary clearance and airway epithelial barrier function was investigated in human airway epithelial cells. Apical exposure to induced an increase in anion secretion that was inhibited by blockers of CFTR and Ca -activated Cl channels. Stimulation of anion secretion was dependent on Ca uptake from the apical solution. exposure also produced an increase in reactive oxygen species (ROS) that was blocked by pretreatment with the oxidant scavenger glutathione (GSH). GSH and the NADPH oxidase inhibitor/complex 1 electron transport inhibitor diphenylene iodonium chloride (DPI) blocked ATP release and the increase in intracellular [Ca ] evoked by also decreased transepithelial resistance, and a portion of this effect was dependent on the increase in ROS. However, the -induced increase in unidirectional dextran (molecular mass = 4,000 Da) flux across the epithelium could not be accounted for by increased oxidative stress. These results support the conclusion that oxidative stress induced by was responsible for regulating Ca -dependent anion secretion and tight junction electrical resistance that would be expected to affect mucociliary clearance.
[Mh] Termos MeSH primário: Alérgenos/farmacologia
Alternaria/química
Cálcio/metabolismo
Células Epiteliais/efeitos dos fármacos
Estresse Oxidativo/efeitos dos fármacos
[Mh] Termos MeSH secundário: Trifosfato de Adenosina/metabolismo
Alternaria/imunologia
Brônquios
Linhagem Celular Transformada
Polaridade Celular
Misturas Complexas/farmacologia
Dextranos/metabolismo
Inibidores Enzimáticos/farmacologia
Células Epiteliais/citologia
Células Epiteliais/imunologia
Glutationa/farmacologia
Seres Humanos
Transporte de Íons/efeitos dos fármacos
NADPH Oxidases/antagonistas & inibidores
NADPH Oxidases/metabolismo
Oniocompostos/farmacologia
Espécies Reativas de Oxigênio/antagonistas & inibidores
Espécies Reativas de Oxigênio/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Allergens); 0 (Complex Mixtures); 0 (Dextrans); 0 (Enzyme Inhibitors); 0 (Onium Compounds); 0 (Reactive Oxygen Species); 6HJ411TU98 (diphenyleneiodonium); 8L70Q75FXE (Adenosine Triphosphate); EC 1.6.3.- (NADPH Oxidases); GAN16C9B8O (Glutathione); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170428
[St] Status:MEDLINE
[do] DOI:10.1152/ajpcell.00043.2017


  9 / 1904 MEDLINE  
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[PMID]:28387738
[Au] Autor:Oksanen E; Chen JC; Fisher SZ
[Ad] Endereço:Science Directorate, European Spallation Source ERIC, Tunavägen 24, 22100 Lund, Sweden. esko.oksanen@esss.se.
[Ti] Título:Neutron Crystallography for the Study of Hydrogen Bonds in Macromolecules.
[So] Source:Molecules;22(4), 2017 Apr 07.
[Is] ISSN:1420-3049
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:The hydrogen bond (H bond) is one of the most important interactions that form the foundation of secondary and tertiary protein structure. Beyond holding protein structures together, H bonds are also intimately involved in solvent coordination, ligand binding, and enzyme catalysis. The H bond by definition involves the light atom, H, and it is very difficult to study directly, especially with X-ray crystallographic techniques, due to the poor scattering power of H atoms. Neutron protein crystallography provides a powerful, complementary tool that can give unambiguous information to structural biologists on solvent organization and coordination, the electrostatics of ligand binding, the protonation states of amino acid side chains and catalytic water species. The method is complementary to X-ray crystallography and the dynamic data obtainable with NMR spectroscopy. Also, as it gives explicit H atom positions, it can be very valuable to computational chemistry where exact knowledge of protonation and solvent orientation can make a large difference in modeling. This article gives general information about neutron crystallography and shows specific examples of how the method has contributed to structural biology, structure-based drug design; and the understanding of fundamental questions of reaction mechanisms.
[Mh] Termos MeSH primário: Substâncias Macromoleculares/química
Modelos Moleculares
Nêutrons
[Mh] Termos MeSH secundário: Cristalografia por Raios X
Enzimas/química
Enzimas/metabolismo
Seres Humanos
Hidrogênio/química
Ligações de Hidrogênio
Hidróxidos/química
Ligantes
Conformação Molecular
Oniocompostos/química
Oxirredução
Ligação Proteica
Proteínas/química
Proteínas/metabolismo
Solventes/química
Especificidade por Substrato
Água/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Enzymes); 0 (Hydroxides); 0 (Ligands); 0 (Macromolecular Substances); 0 (Onium Compounds); 0 (Proteins); 0 (Solvents); 059QF0KO0R (Water); 5046UKT60S (hydronium ion); 7YNJ3PO35Z (Hydrogen); 9159UV381P (hydroxide ion)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170531
[Lr] Data última revisão:
170531
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170408
[St] Status:MEDLINE


  10 / 1904 MEDLINE  
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[PMID]:28215509
[Au] Autor:Xu Y; Wang S; Chan HF; Liu Y; Li H; He C; Li Z; Chen M
[Ad] Endereço:State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China.
[Ti] Título:Triphenylphosphonium-modified poly(ethylene glycol)-poly(ε-caprolactone) micelles for mitochondria- targeted gambogic acid delivery.
[So] Source:Int J Pharm;522(1-2):21-33, 2017 Apr 30.
[Is] ISSN:1873-3476
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Mitochondria are important targets for the intracellular delivery of drugs and DNA. For mitochondria-targeted delivery, a mitochondriotropic molecule, triphenylphosphonium (TPP), was applied to the synthesis of amphiphilic TPP-poly(ethylene glycol)-poly(ε-caprolactone) (TPP-PEG-PCL) polymers. The TPP-PEG-PCL polymer was used to prepare micelles using a solvent evaporation method for the delivery of gambogic acid (GA) (GA-TPP). The micelles were obtained with a favorable particle size of 150.07±11.71nm and an encapsulation efficiency of 80.78±1.36%, and they displayed homogeneous spherical shapes. The GA-TPP micelles exerted enhanced cytotoxic and pro-apoptotic effect against A549 cells compared to free GA and GA-loaded PEG-PCL (GA-PP) micelles, due to the inhibition of the expression of apoptosis-related proteins and promotion of caspase 3/7 and caspase 9 activity. Notably, the mitochondria-targeting GA-TPP micelles selectively accumulated in the mitochondria, inducing the loss of mitochondrial membrane potential and the release of cytochrome c, thereby achieving improved mitochondria-targeting effects. In conclusion, the GA-TPP micelle system shows great promise for lung cancer treatment by inducing an apoptotic effect via the mitochondrial signaling pathway.
[Mh] Termos MeSH primário: Antineoplásicos Fitogênicos/administração & dosagem
Ácido Láctico/química
Mitocôndrias/efeitos dos fármacos
Oniocompostos/química
Poliésteres/química
Ácido Poliglicólico/química
Compostos de Tritil/química
Xantonas/administração & dosagem
[Mh] Termos MeSH secundário: Células A549
Apoptose/efeitos dos fármacos
Proteínas Reguladoras de Apoptose/metabolismo
Caspases/metabolismo
Citocromos c/metabolismo
Sistemas de Liberação de Medicamentos
Seres Humanos
Potencial da Membrana Mitocondrial/efeitos dos fármacos
Micelas
Tamanho da Partícula
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents, Phytogenic); 0 (Apoptosis Regulatory Proteins); 0 (Micelles); 0 (Onium Compounds); 0 (Polyesters); 0 (Trityl Compounds); 0 (Xanthones); 0 (polylactic acid-polyglycolic acid copolymer); 15912-74-0 (triphenylmethylphosphonium); 24980-41-4 (polycaprolactone); 26009-03-0 (Polyglycolic Acid); 33X04XA5AT (Lactic Acid); 8N585K83U2 (gambogic acid); 9007-43-6 (Cytochromes c); EC 3.4.22.- (Caspases)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170816
[Lr] Data última revisão:
170816
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170221
[St] Status:MEDLINE



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