Base de dados : MEDLINE
Pesquisa : D08.811.682.664.750 [Categoria DeCS]
Referências encontradas : 10022 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 1003 ir para página                         

  1 / 10022 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29248751
[Au] Autor:Can NÖ; Osmaniye D; Levent S; Saglik BN; Korkut B; Atli Ö; Özkay Y; Kaplancikli ZA
[Ad] Endereço:Department of Analytical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskisehir, Turkey; Doping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu University, 26470 Eskisehir, Turkey.
[Ti] Título:Design, synthesis and biological assessment of new thiazolylhydrazine derivatives as selective and reversible hMAO-A inhibitors.
[So] Source:Eur J Med Chem;144:68-81, 2018 Jan 20.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:In the recent works, it was shown that numerous thiazolylhydrazine derivatives display hMAO inhibitory activity in the range of micromolar concentration. Hence, in the present study a new series of new thiazole-hydrazines (3a-3n) were designed, synthesized, characterized and screened for their hMAO-A and hMAO-B inhibitory activity by an in vitro flurometric method. The enzyme inhibition assay revealed that most of the synthesized compounds have selective inhibition potency against hMAO-A. The compounds 3f and 3h showed promising hMAO-A inhibition with an IC values of 0.012 µM and 0.011 µM and significant selectivity indexes of 1214 and 1601 towards hMAO-A, respectively. The mechanism of hMAO-A inhibition of compounds 3f and 3h was investigated by Lineweaver-Burk graphics and reversible-competitive inhibition of hMAO-A was determined. Cytotoxicity and genotoxicity studies were carried out and the compound 3h was found as non-cytotoxic and non-genotoxic. Theoretical calculation of ADME properties suggested that synthesized compounds may have a good pharmacokinetic profile. The docking study of compound 3f and 3h revealed that there is a strong interaction between the active sites of hMAO-A and analyzed compound.
[Mh] Termos MeSH primário: Inibidores da Monoaminoxidase/química
Inibidores da Monoaminoxidase/farmacologia
Monoaminoxidase/metabolismo
Tiazóis/química
Tiazóis/farmacologia
[Mh] Termos MeSH secundário: Domínio Catalítico/efeitos dos fármacos
Desenho de Drogas
Seres Humanos
Hidrazinas/química
Hidrazinas/farmacologia
Simulação de Acoplamento Molecular
Monoaminoxidase/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hydrazines); 0 (Monoamine Oxidase Inhibitors); 0 (Thiazoles); EC 1.4.3.4 (Monoamine Oxidase)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171218
[St] Status:MEDLINE


  2 / 10022 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29339253
[Au] Autor:Xiao X; Zhang XX; Zhan MM; Cheng K; Li S; Xie Z; Liao C
[Ad] Endereço:School of Biological and Medical Engineering, Hefei University of Technology, Hefei, Anhui 230009, PR China.
[Ti] Título:Design, synthesis and bioevalucation of novel 2,3-dihydro-1H-inden-1-amine derivatives as potent and selective human monoamine oxidase B inhibitors based on rasagiline.
[So] Source:Eur J Med Chem;145:588-593, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Parkinson's disease (PD) is associated with elevated levels of hMAO-B in the brain, and MAO-B has been recognized a successful target for developing anti-PD drugs. Herein we report rasagiline derivatives as novel potent and selective hMAO-B inhibitors. They were designed by employing fragment-based drug design strategy to link rasagiline and hydrophobic fragments, which may target a hydrophobic pocket in the entrance cavity of hMAO-B. Different linkers such as -OCH -, -SCH -, -OCH CH -, -OCH CH O-, -OCH CH CH O- were tried. A promising selective hMAO-B inhibitor D14 with similar inhibitory activity as rasagiline and improved isoform selectivity was yielded. The selectivity profile of compounds reported herein suggests that we can further develop more potent hMAO-B inhibitors with high isoform selectivity through this strategy.
[Mh] Termos MeSH primário: Aminas/farmacologia
Desenho de Drogas
Indanos/farmacologia
Indenos/farmacologia
Inibidores da Monoaminoxidase/farmacologia
Monoaminoxidase/metabolismo
[Mh] Termos MeSH secundário: Aminas/síntese química
Aminas/química
Cristalografia por Raios X
Relação Dose-Resposta a Droga
Seres Humanos
Indanos/química
Indenos/síntese química
Indenos/química
Modelos Moleculares
Estrutura Molecular
Inibidores da Monoaminoxidase/síntese química
Inibidores da Monoaminoxidase/química
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amines); 0 (Indans); 0 (Indenes); 0 (Monoamine Oxidase Inhibitors); 003N66TS6T (rasagiline); EC 1.4.3.4 (Monoamine Oxidase)
[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:180118
[St] Status:MEDLINE


  3 / 10022 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29335210
[Au] Autor:Tripathi AC; Upadhyay S; Paliwal S; Saraf SK
[Ad] Endereço:Division of Pharmaceutical Chemistry, Faculty of Pharmacy, Babu Banarasi Das Northern India Institute of Technology, Lucknow 226028, UP, India.
[Ti] Título:Privileged scaffolds as MAO inhibitors: Retrospect and prospects.
[So] Source:Eur J Med Chem;145:445-497, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:This review aims to be a comprehensive, authoritative, critical, and readable review of general interest to the medicinal chemistry community because it focuses on the pharmacological, chemical, structural and computational aspects of diverse chemical categories as monoamine oxidase inhibitors (MAOIs). Monoamine oxidases (MAOs), namely MAO-A and MAO-B represent an enormously valuable class of neuronal enzymes embodying neurobiological origin and functions, serving as potential therapeutic target in neuronal pharmacotherapy, and hence we have coined the term "Neurozymes" which is being introduced for the first time ever. Nowadays, therapeutic attention on MAOIs engrosses two imperative categories; MAO-A inhibitors, in certain mental disorders such as depression and anxiety, and MAO-B inhibitors, in neurodegenerative disorders like Alzheimer's disease (AD) and Parkinson's disease (PD). The use of MAOIs declined due to some potential side effects, food and drug interactions, and introduction of other classes of drugs. However, curiosity in MAOIs is reviving and the recent developments of new generation of highly selective and reversible MAOIs, have renewed the therapeutic prospective of these compounds. The initial section of the review emphasizes on the detailed classification, structural and binding characteristics, therapeutic potential, current status and future challenges of the privileged pharmacophores. However, the chemical prospective of privileged scaffolds such as; aliphatic and aromatic amines, amides, hydrazines, azoles, diazoles, tetrazoles, indoles, azines, diazines, xanthenes, tricyclics, benzopyrones, and more interestingly natural products, along with their conclusive SARs have been discussed in the later segment of review. The last segment of the article encompasses some patents granted in the field of MAOIs, in a simplistic way.
[Mh] Termos MeSH primário: Inibidores da Monoaminoxidase/farmacologia
Monoaminoxidase/metabolismo
[Mh] Termos MeSH secundário: Animais
Sítios de Ligação/efeitos dos fármacos
Relação Dose-Resposta a Droga
Seres Humanos
Estrutura Molecular
Inibidores da Monoaminoxidase/química
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Monoamine Oxidase Inhibitors); EC 1.4.3.4 (Monoamine Oxidase)
[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:180117
[St] Status:MEDLINE


  4 / 10022 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29268246
[Au] Autor:Herraiz T; Flores A; Fernández L
[Ad] Endereço:Instituto de Ciencia y Tecnología de Alimentos y Nutrición (ICTAN), Spanish National Research Council (CSIC), Juan de la Cierva 3, 28006, Madrid, Spain. Electronic address: tomas.herraiz@csic.es.
[Ti] Título:Analysis of monoamine oxidase (MAO) enzymatic activity by high-performance liquid chromatography-diode array detection combined with an assay of oxidation with a peroxidase and its application to MAO inhibitors from foods and plants.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1073:136-144, 2018 Jan 15.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Monoamine oxidase (MAO) enzymes catalyze the oxidative deamination of biogenic amines and neurotransmitters and produce ammonia, aldehydes, and hydrogen peroxide which is involved in oxidative processes. Inhibitors of MAO-A and -B isozymes are useful as antidepressants and neuroprotectants. The assays of MAO usually measure amine oxidation products or hydrogen peroxide by spectrophotometric techniques. Those assays are often compromised by interfering compounds resulting in poor results. This research describes a new method that combines in the same assay the oxidative deamination of kynuramine to 4-hydroxyquinoline analyzed by HPLC-DAD with the oxidation of tetramethylbenzidine (TMB) (or Amplex Rex) by horseradish peroxidase (HRP) in presence of hydrogen peroxide. The new method was applied to study the inhibition of human MAO-A and -B by bioactive compounds including ß-carboline alkaloids and flavonoids occurring in foods and plants. As determined by HPLC-DAD, ß-carbolines, methylene blue, kaempferol and clorgyline inhibited MAO-A and methylene blue, 5-nitroindazole, norharman and deprenyl inhibited MAO-B, and all of them inhibited the oxidation of TMB in the same extent. The flavonoids catechin and cyanidin were not inhibitors of MAO by HPLC-DAD but highly inhibited the oxidation of TMB (or Amplex Red) by peroxidase whereas quercetin and resveratrol were moderate inhibitors of MAO-A by HPLC-DAD, but inhibited the peroxidase assay in a higher level. For some phenolic compounds, using the peroxidase-coupled assay to measure MAO activity led to mistaken results. The new method permits to discern between true inhibitors of MAO from those that are antioxidants and which interfere with peroxidase assays but do not inhibit MAO. For true inhibitors of MAO, inhibition as determined by HPLC-DAD correlated well with inhibition of the oxidation of TMB and this approach can be used to assess the in vitro antioxidant activity (less hydrogen peroxide production) resulting from MAO inhibition.
[Mh] Termos MeSH primário: Cromatografia Líquida de Alta Pressão/métodos
Inibidores da Monoaminoxidase/metabolismo
Monoaminoxidase/análise
Monoaminoxidase/metabolismo
Peroxidase/metabolismo
[Mh] Termos MeSH secundário: Antioxidantes/metabolismo
Carbolinas
Flavonoides
Seres Humanos
Cinuramina/análise
Cinuramina/metabolismo
Oxirredução
Extratos Vegetais/análise
Extratos Vegetais/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antioxidants); 0 (Carbolines); 0 (Flavonoids); 0 (Monoamine Oxidase Inhibitors); 0 (Plant Extracts); 363-36-0 (Kynuramine); EC 1.11.1.7 (Peroxidase); EC 1.4.3.4 (Monoamine Oxidase)
[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:171222
[St] Status:MEDLINE


  5 / 10022 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29360121
[Au] Autor:Pregeljc D; Jug U; Mavri J; Stare J
[Ad] Endereço:Theory Department, National Institute of Chemistry, Ljubljana, Slovenia. jernej.stare@ki.si.
[Ti] Título:Why does the Y326I mutant of monoamine oxidase B decompose an endogenous amphetamine at a slower rate than the wild type enzyme? Reaction step elucidated by multiscale molecular simulations.
[So] Source:Phys Chem Chem Phys;20(6):4181-4188, 2018 Feb 07.
[Is] ISSN:1463-9084
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:This work investigates the Y326I point mutation effect on the kinetics of oxidative deamination of phenylethylamine (PEA) catalyzed by the monoamine oxidase B (MAO B) enzyme. PEA is a neuromodulator capable of affecting the plasticity of the brain and is responsible for the mood enhancing effect caused by physical exercise. Due to a similar functionality, PEA is often regarded as an endogenous amphetamine. The rate limiting step of the deamination was simulated at the multiscale level, employing the Empirical Valence Bond approach for the quantum treatment of the involved valence states, whereas the environment (solvated protein) was represented with a classical force field. A comparison of the reaction free energy profiles delivered by simulation of the reaction in the wild type MAO B and its Y326I mutant yields an increase in the barrier by 1.06 kcal mol upon mutation, corresponding to a roughly 6-fold decrease in the reaction rate. This is in excellent agreement with the experimental kinetic studies. Inspection of simulation trajectories reveals possible sources of the point mutation effect, namely vanishing favorable electrostatic interactions between PEA and a Tyr326 side chain and an increased amount of water molecules at the active site due to the replacement of tyrosine by a less spacious isoleucine residue, thereby increasing the dielectric shielding of the catalytic environment provided by the enzyme.
[Mh] Termos MeSH primário: Anfetamina/metabolismo
Monoaminoxidase/metabolismo
[Mh] Termos MeSH secundário: Anfetamina/química
Sítios de Ligação
Biocatálise
Domínio Catalítico
Desaminação
Cinética
Monoaminoxidase/química
Monoaminoxidase/genética
Fenetilaminas/química
Fenetilaminas/metabolismo
Mutação Puntual
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Phenethylamines); CK833KGX7E (Amphetamine); EC 1.4.3.4 (Monoamine Oxidase)
[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:180124
[St] Status:MEDLINE
[do] DOI:10.1039/c7cp07069a


  6 / 10022 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29324067
[Au] Autor:Carradori S; Secci D; Petzer JP
[Ad] Endereço:a Department of Pharmacy , "G. d'Annunzio" University of Chieti-Pescara , Chieti , Italy.
[Ti] Título:MAO inhibitors and their wider applications: a patent review.
[So] Source:Expert Opin Ther Pat;28(3):211-226, 2018 Mar.
[Is] ISSN:1744-7674
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Monoamine oxidase (MAO) inhibitors, after the initial 'golden age', are currently used as third-line antidepressants (selective MAO-A inhibitors) or clinically enrolled as co-adjuvants for neurodegenerative diseases (selective MAO-B inhibitors). However, the research within this field is always increasing due to their pivotal role in modulating synaptic functions and monoamines metabolism. Areas covered: In this paper, MAO inhibitors (2015-2017) are disclosed ordering all the patents according to their chemical scaffold. Structure-activity relationships (SARs) are extrapolated for the most investigated chemotypes (coumarins, pyrazole/oxazepinones, (hetero)arylamides). 108 Compounds are divided into two main groups: newly synthesized molecules and naturally-occurring metabolites. Finally, new therapeutic options are outlined to ensure a more complete view on the potential of these inhibitors. Expert opinion: New proposed MAO inhibitors are endowed with a marked isoform selectivity, with innovative therapeutic potential toward other targets (gliomas, inflammation, muscle dystrophies, migraine, chronic pain, pseudobulbar affect), and with a promising ability to address multi-faceted pathologies such as Alzheimer's disease. The increasing number of patents is analyzed collecting data from 2002 to 2017.
[Mh] Termos MeSH primário: Desenho de Drogas
Inibidores da Monoaminoxidase/farmacologia
Doenças Neurodegenerativas/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Antidepressivos/química
Antidepressivos/farmacologia
Seres Humanos
Monoaminoxidase/efeitos dos fármacos
Monoaminoxidase/metabolismo
Inibidores da Monoaminoxidase/química
Doenças Neurodegenerativas/fisiopatologia
Patentes como Assunto
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antidepressive Agents); 0 (Monoamine Oxidase Inhibitors); EC 1.4.3.4 (Monoamine Oxidase)
[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:180112
[St] Status:MEDLINE
[do] DOI:10.1080/13543776.2018.1427735


  7 / 10022 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29221756
[Au] Autor:Lesniak A; Aarnio M; Diwakarla S; Norberg T; Nyberg F; Gordh T
[Ad] Endereço:Uppsala University, Department of Pharmaceutical Biosciences, SE 751 24 Uppsala, Sweden; Medical University of Warsaw, Department of Pharmacodynamics, Centre for Preclinical Research and Technology, 02-097 Warsaw, Poland. Electronic address: anna.lesniak@wum.edu.pl.
[Ti] Título:Characterization of the binding site for d-deprenyl in human inflamed synovial membrane.
[So] Source:Life Sci;194:26-33, 2018 Feb 01.
[Is] ISSN:1879-0631
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:AIMS: d-Deprenyl when used as a positron emission tomography tracer visualizes peripheral inflammation. The major aim of the current study was to identify and investigate the properties of the binding target for d-deprenyl in synovial membrane explants from arthritic patients. MAIN METHODS: Thirty patients diagnosed with arthritis or osteoarthritis were enrolled into the study. Homologous and competitive radioligand binding assays utilizing [ H]d-deprenyl were performed to investigate the biochemical characteristics of the binding site and assess differences in the binding profile in synovial membranes exhibiting varying levels of inflammation. KEY FINDINGS: The [ H]d-deprenyl binding assay confirmed the existence of a single, saturable population of membrane-bound protein binding sites in synovial membrane homogenates. The macroscopically determined level of inflammation correlated with an increase in [ H]d-deprenyl binding affinity, without significant alterations in binding site density. Selective monoamine oxidase B inhibitor, selegiline competed for the same site as [ H]d-deprenyl, but failed to differentiate the samples with regard to their inflammation grade. A monoamine oxidase A inhibitor, pirlindole mesylate showed only weak displacement of [ H]d-deprenyl binding. No significant alterations in monoamine oxidase B expression was detected, thus it was not confirmed whether it could serve as a marker for ongoing inflammation. SIGNIFICANCE: Our study was the first to show the biochemical characteristics of the [ H]d-deprenyl binding site in inflamed human synovium. We confirmed that d-deprenyl could differentiate between patients with varying severity of synovitis in the knee joint by binding to a protein target distinct from monoamine oxidase B.
[Mh] Termos MeSH primário: Artrite/diagnóstico
Inibidores da Monoaminoxidase/metabolismo
Monoaminoxidase/análise
Selegilina/metabolismo
Membrana Sinovial/patologia
Sinovite/diagnóstico
[Mh] Termos MeSH secundário: Idoso
Artrite/metabolismo
Sítios de Ligação
Feminino
Seres Humanos
Masculino
Meia-Idade
Monoaminoxidase/metabolismo
Tomografia por Emissão de Pósitrons
Ensaio Radioligante
Membrana Sinovial/metabolismo
Sinovite/metabolismo
Trítio/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Monoamine Oxidase Inhibitors); 10028-17-8 (Tritium); 2K1V7GP655 (Selegiline); EC 1.4.3.4 (Monoamine Oxidase)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171210
[St] Status:MEDLINE


  8 / 10022 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
[PMID]:29368831
[Au] Autor:Atramentova LA; Luchko EN
[Ti] Título:[Aggression and empathy as genetic differentiation factors of urban population].
[So] Source:Genetika;52(6):705-12, 2016 Jun.
[Is] ISSN:0016-6758
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Ab] Resumo:Permanent residents of Kharkiv (637 men and 856 women at the age of 45­65 years) are tested on the level of aggression and empathy. The average aggression level (41.7 points) is higher in migrants (born outside Kharkiv) than in indigenous people (36.3 points); the average empathy level is lower in migrants (3.2 points) than in indigenous people (5.5 points). The average values of the aggression and empathy indices are not associated with ethnicity and degree of miscegenation. The correlation between spouses (r) by these personal features is within 0.20­0.31; the marriage conjugation index (K) is 0.13­0.18. Genotyping of the married couples for the rs2235186 SNP of X-linked monoaminooxidase (MAO-A) gene detected a positive marriage assortativeness: the C × CC and T × TT pairs are developed more frequently than during panmixia; the C × TT and T × CC pairs, less frequently. The T allele is coupled with increased aggression level and decreased empathy level. The phenotypes of heterozygous women indicate the intermediate inheritance of these traits.
[Mh] Termos MeSH primário: Agressão
Empatia/genética
Monoaminoxidase/genética
Polimorfismo de Nucleotídeo Único
População Urbana
[Mh] Termos MeSH secundário: Idoso
Feminino
Seres Humanos
Masculino
Meia-Idade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 1.4.3.4 (Monoamine Oxidase); EC 1.4.3.4. (monoamine oxidase A, human)
[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:180126
[St] Status:MEDLINE


  9 / 10022 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28448446
[Au] Autor:Wu Y; Wang L; Deng D; Zhang Q; Liu W
[Ad] Endereço:Department of Nephrology, Affiliated Beijing Friendship Hospital, Faculty of Kidney Diseases, Capital Medical University, No. 95 Yong An Road, Xi Cheng District, Beijing 100050, China. wyryyyy@163.com.
[Ti] Título:Renalase Protects against Renal Fibrosis by Inhibiting the Activation of the ERK Signaling Pathways.
[So] Source:Int J Mol Sci;18(5), 2017 Apr 27.
[Is] ISSN:1422-0067
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Renal interstitial fibrosis is a common pathway for the progression of chronic kidney disease (CKD) to end-stage renal disease. Renalase, acting as a signaling molecule, has been reported to have cardiovascular and renal protective effects. However, its role in renal fibrosis remains unknown. In this study, we evaluated the therapeutic efficacy of renalase in rats with complete unilateral ureteral obstruction (UUO) and examined the inhibitory effects of renalase on transforming growth factor-ß1 (TGF-ß1)-induced epithelial-mesenchymal transition (EMT) in human proximal renal tubular epithelial (HK-2) cells. We found that in the UUO model, the expression of renalase was markedly downregulated and adenoviral-mediated expression of renalase significantly attenuated renal interstitial fibrosis, as evidenced by the maintenance of E-cadherin expression and suppressed expression of α-smooth muscle actin (α-SMA), fibronectin and collagen-I. In vitro, renalase inhibited TGF-ß1-mediated upregulation of α-SMA and downregulation of E-cadherin. Increased levels of Phospho-extracellular regulated protein kinases (p-ERK1/2) in TGF-ß1-stimulated cells were reversed by renalase cotreatment. When ERK1 was overexpressed, the inhibition of TGF-ß1-induced EMT and fibrosis mediated by renalase was attenuated. Our study provides the first evidence that renalase can ameliorate renal interstitial fibrosis by suppression of tubular EMT through inhibition of the ERK pathway. These results suggest that renalase has potential renoprotective effects in renal interstitial fibrosis and may be an effective agent for slowing CKD progression.
[Mh] Termos MeSH primário: Sistema de Sinalização das MAP Quinases/fisiologia
Monoaminoxidase/metabolismo
[Mh] Termos MeSH secundário: Adenoviridae/genética
Animais
Linhagem Celular
Modelos Animais de Doenças
Regulação para Baixo
Transição Epitelial-Mesenquimal/efeitos dos fármacos
Fibronectinas/metabolismo
Fibrose/fisiopatologia
Vetores Genéticos/genética
Vetores Genéticos/metabolismo
Seres Humanos
Nefropatias/etiologia
Nefropatias/metabolismo
Nefropatias/patologia
Masculino
Proteína Quinase 1 Ativada por Mitógeno/genética
Proteína Quinase 1 Ativada por Mitógeno/metabolismo
Proteína Quinase 3 Ativada por Mitógeno/genética
Proteína Quinase 3 Ativada por Mitógeno/metabolismo
Monoaminoxidase/sangue
Monoaminoxidase/genética
Ratos
Ratos Sprague-Dawley
Fator de Crescimento Transformador beta1/farmacologia
Regulação para Cima
Obstrução Ureteral/complicações
Obstrução Ureteral/metabolismo
Obstrução Ureteral/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fibronectins); 0 (Transforming Growth Factor beta1); EC 1.4.3.4 (Monoamine Oxidase); EC 1.4.3.4. (renalase); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180122
[Lr] Data última revisão:
180122
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170428
[St] Status:MEDLINE


  10 / 10022 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29227084
[Au] Autor:Gudkova OO; Latyshko NV; Shandrenko SG
[Ti] Título:Amine oxidases as important agents of pathological processes of rhabdomyolysis in rats.
[So] Source:Ukr Biochem J;88(1):79-87, 2016 Jan-Feb.
[Is] ISSN:2409-4943
[Cp] País de publicação:Ukraine
[La] Idioma:eng
[Ab] Resumo:In this study we have tested an idea on the important role of amine oxidases (semicarbazide-sensitive amine oxidase, diamine oxidase, polyamine oxidase) as an additional source of oxidative/carbonyl stress under glycerol-induced rhabdomyolysis, since the enhanced formation of reactive oxygen species and reactive carbonyl species in a variety of tissues is linked to various diseases. In our experiments we used the sensitive fluorescent method devised for estimation of amine oxidases activity in the rat kidney and thymus as targeted organs under rhabdomyolysis. We have found in vivo the multiple rises in activity of semicarbazide-sensitive amine oxidase, diamine oxidase, polyamine oxidase (2-4.5 times) in the corresponding cell fractions, whole cells or their lysates at the 3-6th day after glycerol injection. Aberrant antioxidant activities depended on rhabdomyolysis stage and had organ specificity. Additional treatment of animals with metal chelator 'Unithiol' adjusted only the activity of antioxidant enzymes but not amine oxidases in both organs. Furthermore the in vitro experiment showed that Fenton reaction (hydrogen peroxide in the presence of iron) products alone had no effect on semicarbazide-sensitive amine oxidase activity in rat liver cell fraction whereas supplementation with methylglyoxal resulted in its significant 2.5-fold enhancement. Combined action of the both agents had additive effect on semicarbazide-sensitive amine oxidase activity. We can assume that biogenic amine and polyamine catabolism by amine oxidases is upregulated by oxidative and carbonyl stress factors directly under rhabdomyolysis progression, and the increase in catabolic products concentration contributes to tissue damage in glycerol-induced acute renal failure and apoptosis stimulation in thymus.
[Mh] Termos MeSH primário: Amina Oxidase (contendo Cobre)/metabolismo
Monoaminoxidase/metabolismo
Oxirredutases atuantes sobre Doadores de Grupo CH-NH/metabolismo
Espécies Reativas de Oxigênio/metabolismo
Rabdomiólise/enzimologia
[Mh] Termos MeSH secundário: Animais
Quelantes/farmacologia
Glicerol
Hepatócitos/efeitos dos fármacos
Hepatócitos/enzimologia
Hepatócitos/patologia
Peróxido de Hidrogênio/antagonistas & inibidores
Peróxido de Hidrogênio/farmacologia
Rim/efeitos dos fármacos
Rim/enzimologia
Rim/patologia
Fígado/efeitos dos fármacos
Fígado/enzimologia
Fígado/patologia
Masculino
Especificidade de Órgãos
Oxirredução
Carbonilação Proteica
Aldeído Pirúvico/antagonistas & inibidores
Aldeído Pirúvico/farmacologia
Ratos
Ratos Wistar
Rabdomiólise/induzido quimicamente
Rabdomiólise/tratamento farmacológico
Rabdomiólise/patologia
Semicarbazidas/antagonistas & inibidores
Semicarbazidas/farmacologia
Timo/efeitos dos fármacos
Timo/enzimologia
Timo/patologia
Unitiol/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Chelating Agents); 0 (Reactive Oxygen Species); 0 (Semicarbazides); 37QUC23K2X (carbamylhydrazine); 4076-02-2 (Unithiol); 722KLD7415 (Pyruvaldehyde); BBX060AN9V (Hydrogen Peroxide); EC 1.4.3.21 (Amine Oxidase (Copper-Containing)); EC 1.4.3.4 (Monoamine Oxidase); EC 1.5.- (Oxidoreductases Acting on CH-NH Group Donors); EC 1.5.3.- (polyamine oxidase); PDC6A3C0OX (Glycerol)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180116
[Lr] Data última revisão:
180116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171212
[St] Status:MEDLINE
[do] DOI:10.15407/ubj88.01.079



página 1 de 1003 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