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  1 / 3257 MEDLINE  
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[PMID]:29443789
[Au] Autor:Zhu L; He Y; Niu F; Yan M; Li J; Yuan D; Jin T
[Ad] Endereço:Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region.
[Ti] Título:Polymorphisms of drug-metabolizing enzyme CYP2E1 in Chinese Uygur population.
[So] Source:Medicine (Baltimore);97(7):e9970, 2018 Feb.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Pharmacogenetics is the genetic basis of pharmacokinetics, genetic testing, and clinical management in diseases. Evaluation about genetic alterations of drug metabolizing enzymes in human genome contributes toward understanding the interindividual and interethnic variability for clinical response to potential toxicants. CYP2E1 gene encodes a drug-metabolizing enzyme that metabolizes mostly small, polar molecules, including toxic laboratory chemicals. The aim of this study was to investigate CYP2E1 polymorphisms and gene profile in a Chinese Uygur population. Frequencies for the CYP2E1 mutated alleles and genotypes were screened in 100 unrelated random healthy Uygur volunteers. PCR and direct sequencing revealed a total of 32 polymorphisms, of which 5 novel mutations were presented. Rs 943975 was the most common single nucleotide polymorphism (SNP). The allele frequencies of CYP2E11A, 4, 7A, and 7C were 65.5, 2, 19.5, and 13%, respectively. The most common genotype combinations were CYP2C191A/1A (43%) and 1A/7C (24%). Functional prediction for 2 nonsynonymous mutations G173S and V179I was performed using MutationTaster, sorting intolerant from tolerant, and PolyPhen-2. The observations of the present study give rise to useful information on CYP2E1 polymorphisms in Chinese Uygur individuals. The results suggest important clinical implications for the use of medications metabolized by CYP2E1 among Uygurs.
[Mh] Termos MeSH primário: Grupo com Ancestrais do Continente Asiático/genética
Citocromo P-450 CYP2E1/genética
Frequência do Gene
Mutação
Polimorfismo de Nucleotídeo Único
[Mh] Termos MeSH secundário: Adulto
China
Feminino
Genótipo
Seres Humanos
Desequilíbrio de Ligação
Masculino
Meia-Idade
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
EC 1.14.13.- (Cytochrome P-450 CYP2E1)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180215
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009970


  2 / 3257 MEDLINE  
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[PMID]:29381998
[Au] Autor:Wang L; Ren G; Li J; Zhu L; Niu F; Yan M; Li J; Yuan D; Jin T
[Ad] Endereço:Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi.
[Ti] Título:Genetic polymorphism analysis of cytochrome P4502E1 (CYP2E1) in a Chinese Tibetan population.
[So] Source:Medicine (Baltimore);96(47):e8855, 2017 Nov.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cytochrome P4502E1 (CYP2E1) gene genetic polymorphisms vary markedly in frequency among different ethnic and racial groups.We studied the genotype distributions and allele frequencies of 3 CYP2E1 polymorphisms: CYP2E11A, CYP2E17A, and CYP2E17C by polymerase chain reaction technique in a sample of 100 healthy subjects representing Tibetan population.The frequencies of CYP2E11A, 7A, and 7C alleles were 0.705, 0.125, and 0.170, respectively. Compared with other populations, we found that the allele frequencies of the variants -352A>G (rs2070672) and -333A>T (rs2070673) in this Tibetan population have significant differences compared with European-American, African-American, Japanese, Korean, and other different geographic areas in Chinese Han population. Furthermore, the results of protein prediction revealed that the variant 6397G>A (rs61710826) could influence the protein structure and function.These findings in this study would be valuable for pharmacogenetics for drug therapy and drug discovery. However, further studies in larger samples are warranted to confirm our results.
[Mh] Termos MeSH primário: Grupo com Ancestrais do Continente Asiático/genética
Citocromo P-450 CYP2E1/genética
Grupos Étnicos/genética
Polimorfismo de Nucleotídeo Único/genética
[Mh] Termos MeSH secundário: Alelos
Feminino
Frequência do Gene
Genótipo
Voluntários Saudáveis
Seres Humanos
Desequilíbrio de Ligação
Masculino
Reação em Cadeia da Polimerase
Tibet/etnologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 1.14.13.- (Cytochrome P-450 CYP2E1)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180209
[Lr] Data última revisão:
180209
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180201
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000008855


  3 / 3257 MEDLINE  
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[PMID]:29227611
[Au] Autor:Rushchak VV; Chashchyn MO
[Ti] Título:Cytochrome P450 2E1 participation in the pathogenesis of experimental metabolic syndrome in guinea pigs.
[So] Source:Ukr Biochem J;88(2):98-106, 2016 Mar-Apr.
[Is] ISSN:2409-4943
[Cp] País de publicação:Ukraine
[La] Idioma:eng
[Ab] Resumo:In this work the experimental metabolic syndrome on the basis of protamine sulfate modeling in guinea pigs was reproduced and pathological processes in the liver of experimental animals were studied. We determined the level of free radicals and markers of liver damage in the blood of experimental animals. We investigated the liver glycogen content and K+,Na+-ATPase activity in the liver of experimental animals as well as measured the cytochrome P450 2E1 (CY P2E1) expression ­ one of the main factors of oxidative stress. Evidence of development of hepatotoxic processes, increasing of the CY P2E1 level as well as of the free radical level in the animals with metabolic syndrome were found. Using of CY P2E1 inhibitors had shown that the free radical level in the blood of experimental animals depended on the level of the enzyme expression and activity. The obtained results suggest that the changes in the CY P2E1 expression play an important role in the development of hepatotoxic processes upon experimental metabolic syndrome. It was assumed that pharmacological correction of the enzyme expression may be an important mechanism for the influence on the metabolic syndrome clinical course.
[Mh] Termos MeSH primário: Inibidores do Citocromo P-450 CYP2E1/farmacologia
Citocromo P-450 CYP2E1/genética
Fígado/efeitos dos fármacos
Síndrome Metabólica/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Citocromo P-450 CYP2E1/metabolismo
Dissulfiram/farmacologia
Radicais Livres/antagonistas & inibidores
Radicais Livres/metabolismo
Regulação da Expressão Gênica
Glicogênio/metabolismo
Cobaias
Fígado/enzimologia
Fígado/patologia
Masculino
Síndrome Metabólica/induzido quimicamente
Síndrome Metabólica/enzimologia
Síndrome Metabólica/patologia
Estresse Oxidativo/efeitos dos fármacos
Protaminas
Pirazóis/farmacologia
Quercetina/farmacologia
ATPase Trocadora de Sódio-Potássio/genética
ATPase Trocadora de Sódio-Potássio/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cytochrome P-450 CYP2E1 Inhibitors); 0 (Free Radicals); 0 (Protamines); 0 (Pyrazoles); 83LCM6L2BY (fomepizole); 9005-79-2 (Glycogen); 9IKM0I5T1E (Quercetin); EC 1.14.13.- (Cytochrome P-450 CYP2E1); EC 3.6.3.9 (Sodium-Potassium-Exchanging ATPase); TR3MLJ1UAI (Disulfiram)
[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/ubj88.02.098


  4 / 3257 MEDLINE  
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[PMID]:28463483
[Au] Autor:Legault EK; James CA; Stewart K; Muiznieks I; Doty SL; Strand SE
[Ad] Endereço:Department of Civil and Environmental Engineering, UW Box 355014, University of Washington , Seattle, Washington, United States.
[Ti] Título:A Field Trial of TCE Phytoremediation by Genetically Modified Poplars Expressing Cytochrome P450 2E1.
[So] Source:Environ Sci Technol;51(11):6090-6099, 2017 Jun 06.
[Is] ISSN:1520-5851
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A controlled field study was performed to evaluate the effectiveness of transgenic poplars for phytoremediation. Three hydraulically contained test beds were planted with 12 transgenic poplars, 12 wild type (WT) poplars, or left unplanted, and dosed with equivalent concentrations of trichloroethylene (TCE). Removal of TCE was enhanced in the transgenic tree bed, but not to the extent of the enhanced removal observed in laboratory studies. Total chlorinated ethene removal was 87% in the CYP2E1 bed, 85% in the WT bed, and 34% in the unplanted bed in 2012. Evapotranspiration of TCE from transgenic leaves was reduced by 80% and diffusion of TCE from transgenic stems was reduced by 90% compared to WT. Cis-dichloroethene and vinyl chloride levels were reduced in the transgenic tree bed. Chloride ion accumulated in the planted beds corresponding to the TCE loss, suggesting that contaminant dehalogenation was the primary loss fate.
[Mh] Termos MeSH primário: Biodegradação Ambiental
Populus/enzimologia
Tricloroetileno
[Mh] Termos MeSH secundário: Citocromo P-450 CYP2E1/metabolismo
Árvores
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
290YE8AR51 (Trichloroethylene); EC 1.14.13.- (Cytochrome P-450 CYP2E1)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171211
[Lr] Data última revisão:
171211
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1021/acs.est.5b04758


  5 / 3257 MEDLINE  
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[PMID]:29049217
[Au] Autor:Hu B; Shi C; Jiang HX; Qin SY
[Ad] Endereço:Department of Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning, China.
[Ti] Título:Identification of novel therapeutic target genes and pathway in pancreatic cancer by integrative analysis.
[So] Source:Medicine (Baltimore);96(42):e8261, 2017 Oct.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Gene alterations are crucial to the molecular pathogenesis of pancreatic cancer. The present study was designed to identify the potential candidate genes in the pancreatic carcinogenesis. METHODS: Gene Expression Omnibus database (GEO) datasets of pancreatic cancer tissue were retrieval and the differentially expressed genes (DEGs) from individual microarray data were merged. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, protein-protein interaction (PPI) networks, and gene coexpression analysis were performed. RESULTS: Three GEO datasets, including 74 pancreatic cancer samples and 55 controls samples were selected. A total of 2325 DEGs were identified, including 1383 upregulated and 942 downregulated genes. The GO terms for molecular functions, biological processes, and cellular component were protein binding, small molecule metabolic process, and integral to membrane, respectively. The most significant pathway in KEGG analysis was metabolic pathways. PPI network analysis indicated that the significant hub genes including cytochrome P450, family 2, subfamily E, polypeptide 1 (CYP2E1), mitogen-activated protein kinase 3 (MAPK3), and phospholipase C, gamma 1 (PLCG1). Gene coexpression network analysis identified 4 major modules, and the potassium channel tetramerization domain containing 10 (KCTD10), kin of IRRE like (KIRREL), dipeptidyl-peptidase 10 (DPP10), and unc-80 homolog (UNC80) were the hub gene of each modules, respectively. CONCLUSION: Our integrative analysis provides a comprehensive view of gene expression patterns associated with the pancreatic carcinogenesis.
[Mh] Termos MeSH primário: Carcinogênese/genética
Regulação Neoplásica da Expressão Gênica/genética
Neoplasias Pancreáticas/genética
[Mh] Termos MeSH secundário: Proteínas de Transporte/genética
Estudos de Casos e Controles
Citocromo P-450 CYP2E1/genética
Bases de Dados Genéticas
Dipeptidil Peptidases e Tripeptidil Peptidases/genética
Perfilação da Expressão Gênica/métodos
Ontologia Genética
Seres Humanos
Proteínas de Membrana/genética
Proteína Quinase 3 Ativada por Mitógeno/genética
Fosfolipase C gama/genética
Canais de Potássio de Abertura Dependente da Tensão da Membrana/genética
Mapas de Interação de Proteínas
Transdução de Sinais/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carrier Proteins); 0 (KCTD10 protein, human); 0 (KIRREL protein, human); 0 (Membrane Proteins); 0 (Potassium Channels, Voltage-Gated); 0 (Unc80 protein, human); EC 1.14.13.- (Cytochrome P-450 CYP2E1); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3); EC 3.1.4.11 (PLCG1 protein, human); EC 3.1.4.3 (Phospholipase C gamma); EC 3.4.14.- (DPP10 protein, human); EC 3.4.14.- (Dipeptidyl-Peptidases and Tripeptidyl-Peptidases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171122
[Lr] Data última revisão:
171122
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171020
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000008261


  6 / 3257 MEDLINE  
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[PMID]:28904078
[Au] Autor:Davydov DR; Davydova NY; Rodgers JT; Rushmore TH; Jones JP
[Ad] Endereço:Department of Chemistry, Washington State University, Pullman, WA 99164, U.S.A. dmrdavyd@gmail.com.
[Ti] Título:Toward a systems approach to the human cytochrome P450 ensemble: interactions between CYP2D6 and CYP2E1 and their functional consequences.
[So] Source:Biochem J;474(20):3523-3542, 2017 Oct 10.
[Is] ISSN:1470-8728
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Functional cross-talk among human drug-metabolizing cytochrome P450 through their association is a topic of emerging importance. Here, we studied the interactions of human CYP2D6, a major metabolizer of psychoactive drugs, with one of the most prevalent human P450 enzymes, ethanol-inducible CYP2E1. Detection of P450-P450 interactions was accomplished through luminescence resonance energy transfer between labeled proteins incorporated into human liver microsomes and the microsomes of insect cells containing NADPH-cytochrome P450 reductase. The potential of CYP2D6 to form oligomers in the microsomal membrane is among the highest observed with human cytochrome P450 studied up to date. We also observed the formation of heteromeric complexes of CYP2D6 with CYP2E1 and CYP3A4, and found a significant modulation of these interactions by 3,4-methylenedioxymethylamphetamine, a widespread drug of abuse metabolized by CYP2D6. Our results demonstrate an ample alteration of the catalytic properties of CYP2D6 and CYP2E1 caused by their association. In particular, we demonstrated that preincubation of microsomes containing co-incorporated CYP2D6 and CYP2E1 with CYP2D6-specific substrates resulted in considerable time-dependent activation of CYP2D6, which presumably occurs via a slow substrate-induced reorganization of CYP2E1-CYP2D6 hetero-oligomers. Furthermore, we demonstrated that the formation of heteromeric complexes between CYP2E1 and CYP2D6 affects the stoichiometry of futile cycling and substrate oxidation by CYP2D6 by means of decreasing the electron leakage through the peroxide-generating pathways. Our results further emphasize the role of P450-P450 interactions in regulatory cross-talk in human drug-metabolizing ensemble and suggest a role of interactions of CYP2E1 with CYP2D6 in pharmacologically important instances of alcohol-drug interactions.
[Mh] Termos MeSH primário: Citocromo P-450 CYP2D6/química
Citocromo P-450 CYP2D6/metabolismo
Citocromo P-450 CYP2E1/química
Citocromo P-450 CYP2E1/metabolismo
[Mh] Termos MeSH secundário: Animais
Bovinos
Seres Humanos
Microssomos Hepáticos/metabolismo
Ligação Proteica/fisiologia
Estrutura Secundária de Proteína
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 1.14.13.- (Cytochrome P-450 CYP2E1); EC 1.14.14.1 (Cytochrome P-450 CYP2D6)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171110
[Lr] Data última revisão:
171110
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170915
[St] Status:MEDLINE
[do] DOI:10.1042/BCJ20170543


  7 / 3257 MEDLINE  
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[PMID]:28803882
[Au] Autor:Tanaka Y; Fujii W; Hori H; Kitagawa Y; Ozaki K
[Ad] Endereço:Suntory MONOZUKURI Expert Limited, 8-1-1 Seikadai Seika-cho, Soraku-gun, Kyoto 619-0238, Japan; Laboratory of Pathology, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge, Hirakata, Osaka 573-0101, Japan.
[Ti] Título:Changes in coumarin kinetics and subcellular localization of CYP2E1 contribute to bile duct damage and reduce hepatocellular damage after repeated administration of coumarin in rats.
[So] Source:Toxicol Lett;280:99-105, 2017 Oct 05.
[Is] ISSN:1879-3169
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Coumarin exhibits different hepatotoxicity in rats depending on the administration frequency. To investigate the underlying mechanisms for the differences, we administered coumarin to rats as a single dose or repeatedly for 4 weeks. We found large increases in blood levels of liver enzymes and noticeable centrilobular hepatic necrosis after a single dose of coumarin. After repeated administration, enzyme levels mildly increased, while those of γ-GTP and total bilirubin significantly increased, suggesting bile duct damage. In the control group, cytochrome P450 2E1 (CYP2E1) showed a diffuse subcellular distribution but accumulated within the hepatocyte endoplasmic reticulum after repeated coumarin administration. The maximum blood concentrations of coumarin and its metabolites were significantly lower upon repeated administration. The results suggest that changes in coumarin pharmacokinetics and CYP2E1 subcellular distribution contribute to resistance to coumarin-induced hepatic necrosis, while cytotoxicity of metabolic conjugates shown in vitro may contribute to bile duct damage upon repeated coumarin administration.
[Mh] Termos MeSH primário: Ductos Biliares/efeitos dos fármacos
Cumarínicos/toxicidade
Citocromo P-450 CYP2E1/metabolismo
[Mh] Termos MeSH secundário: Animais
Ductos Biliares/patologia
Cumarínicos/sangue
Cumarínicos/metabolismo
Citocromo P-450 CYP2E1/genética
Regulação Enzimológica da Expressão Gênica/fisiologia
Células Hep G2
Hepatócitos/efeitos dos fármacos
Seres Humanos
Masculino
Transporte Proteico
Distribuição Aleatória
Ratos
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Coumarins); A4VZ22K1WT (coumarin); EC 1.14.13.- (Cytochrome P-450 CYP2E1)
[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:170815
[St] Status:MEDLINE


  8 / 3257 MEDLINE  
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[PMID]:28803762
[Au] Autor:Wang F; Liu JC; Zhou RJ; Zhao X; Liu M; Ye H; Xie ML
[Ad] Endereço:Department of Pharmacology, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, Jiangsu Province, China.
[Ti] Título:Apigenin protects against alcohol-induced liver injury in mice by regulating hepatic CYP2E1-mediated oxidative stress and PPARα-mediated lipogenic gene expression.
[So] Source:Chem Biol Interact;275:171-177, 2017 Sep 25.
[Is] ISSN:1872-7786
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Alcohol is a major cause of liver injury, and there are currently no ideal pharmacological reagents that can prevent or reverse this disease. Apigenin is one of the most common flavonoids present in numerous plants and has many beneficial effects. But whether or not apigenin may protect against alcohol-induced liver injury remains unknown. Our aim was to examine the effect and potential mechanisms. The experimental mice were given 56% erguotou wine or simultaneously given apigenin 150-300 mg/kg by gavage for 30 days. The results showed that in the apigenin-treated mice, the expression of hepatic cytochrome P450 2E1 (CYP2E1) and nuclear factor kappa B proteins as well as contents of hepatic malondialdehyde and tumor necrosis factor-alpha were reduced, while the levels of hepatic reduced glutathione, glutathione reductase, glutathione peroxidase, and glutathione S-transferase were increased, especially in the 300 mg/kg group. A significant change in hepatic steatosis was also observed in the apigenin 300 mg/kg group. Apigenin pretreatment could increase the expression of hepatic peroxisome proliferator-activated receptor alpha (PPARα) and carnitine palmitoyltransferase-1 proteins, and decrease the expression of hepatic sterol regulatory element binding protein-1c, fatty acid synthase, and diacylglycerol acyltransferase proteins. These findings demonstrated that apigenin might exert a protective effect on alcohol-induced liver injury, and its mechanisms might be related to the regulations of hepatic CYP2E1-mediated oxidative stress and PPARα-mediated lipogenic gene expression.
[Mh] Termos MeSH primário: Apigenina/farmacologia
Citocromo P-450 CYP2E1/metabolismo
Regulação da Expressão Gênica/efeitos dos fármacos
Hepatopatias Alcoólicas/prevenção & controle
Estresse Oxidativo/efeitos dos fármacos
PPAR alfa/metabolismo
Substâncias Protetoras/farmacologia
[Mh] Termos MeSH secundário: Animais
Apigenina/uso terapêutico
Etanol/toxicidade
Ácido Graxo Sintases/metabolismo
Glutationa/metabolismo
Glutationa Peroxidase/metabolismo
Glutationa Redutase/metabolismo
Glutationa Transferase/metabolismo
Hepatopatias Alcoólicas/etiologia
Hepatopatias Alcoólicas/patologia
Masculino
Malondialdeído/metabolismo
Camundongos
PPAR alfa/genética
Substâncias Protetoras/uso terapêutico
Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
Fator de Transcrição RelA/metabolismo
Fator de Necrose Tumoral alfa/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (PPAR alpha); 0 (Protective Agents); 0 (Sterol Regulatory Element Binding Protein 1); 0 (Transcription Factor RelA); 0 (Tumor Necrosis Factor-alpha); 3K9958V90M (Ethanol); 4Y8F71G49Q (Malondialdehyde); 7V515PI7F6 (Apigenin); EC 1.11.1.9 (Glutathione Peroxidase); EC 1.14.13.- (Cytochrome P-450 CYP2E1); EC 1.8.1.7 (Glutathione Reductase); EC 2.3.1.85 (Fatty Acid Synthases); EC 2.5.1.18 (Glutathione Transferase); GAN16C9B8O (Glutathione)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170815
[St] Status:MEDLINE


  9 / 3257 MEDLINE  
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[PMID]:28756226
[Au] Autor:Kumar S; Sinha N; Gerth KA; Rahman MA; Yallapu MM; Midde NM
[Ad] Endereço:Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA. Electronic address: ksantosh@uthsc.edu.
[Ti] Título:Specific packaging and circulation of cytochromes P450, especially 2E1 isozyme, in human plasma exosomes and their implications in cellular communications.
[So] Source:Biochem Biophys Res Commun;491(3):675-680, 2017 Sep 23.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cytochrome P450 (CYP) enzymes metabolize the majority of xenobiotics and are mainly found in hepatic and some extra-hepatic cells. However, their presence and functional role in exosomes, small extracellular vesicles that are secreted from various cells into extracellular fluids including plasma, is unknown. In this study, we analyzed the expression and biological activity of CYP enzymes in human plasma exosomes. First, we optimized isolation of plasma exosomes and characterized them for their physical properties and quality. The results showed that the purity of exosomes (<200 nm) improved upon prior filtration of plasma using a 0.22 micron filter. We then analyzed the relative level of exosomal CYP mRNAs, proteins, and enzyme activity. The results showed that the relative level of CYP enzymes in exosomes is higher than in plasma, suggesting their specific packaging in exosomes. Of the seven CYP enzymes tested, the mRNA of CYP1B1, CYP2A6, CYP2E1, and CYP3A4 were detectable in exosomes. Interestingly, the relative level of CYP2E1 mRNA was >500-fold higher than the other CYPs. The results from the Western blot showed detectable levels of CYP1A1, CYP1B1, CYP2A6, CYP2E1, and CYP3A4. Our results also demonstrated that exosomal CYP2E1 and CYP3A4 show appreciable activity relative to their respective positive controls (CYP-induced baculosomes). Our results also showed that CYP2E1 is expressed relatively higher in plasma exosomes than hepatic and monocytic cells and exosomes derived from these cells. In conclusion, this is the first evidence of the specific packaging and circulation of CYP enzymes, especially CYP2E1, in human plasma exosomes. The findings have biological and clinical significance in terms of their implications in cellular communications and potential use of plasma exosomal CYPs as biomarkers.
[Mh] Termos MeSH primário: Proteínas Sanguíneas/metabolismo
Comunicação Celular/fisiologia
Citocromo P-450 CYP2E1/metabolismo
Sistema Enzimático do Citocromo P-450/sangue
Exossomos/enzimologia
[Mh] Termos MeSH secundário: Ativação Enzimática
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Blood Proteins); 9035-51-2 (Cytochrome P-450 Enzyme System); EC 1.14.13.- (Cytochrome P-450 CYP2E1)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170911
[Lr] Data última revisão:
170911
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170731
[St] Status:MEDLINE


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[PMID]:28650933
[Au] Autor:Chang LS; Hsu YW; Lu CC; Lo MH; Hsieh KS; Li SC; Chang WC; Kuo HC
[Ad] Endereço:From the *Department of Pediatrics and Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital, and †Chang Gung University College of Medicine, and ‡Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan City, Taiwan; §The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, and ¶Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan; ‖Division of Colorectal Surgery, Department of Surgery, and **Genomics and Proteomics Core Laboratory, Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; ††Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan; ‡‡Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Kaohsiung, Taiwan; §§Department of Pharmacy, Taipei Medical University-Wanfang Hospital, Taipei, Taiwan.
[Ti] Título:CYP2E1 Gene Polymorphisms Related to the Formation of Coronary Artery Lesions in Kawasaki Disease.
[So] Source:Pediatr Infect Dis J;36(11):1039-1043, 2017 Nov.
[Is] ISSN:1532-0987
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Kawasaki disease (KD) is an acute febrile systemic vasculitis that disturbs coronary arteries. Patients' risks of adverse cardiovascular events and subclinical atherosclerosis have been found to significantly increase with polymorphisms of the human cytochrome P450. This current study aims to research the possible relationship between cytochrome P450, family 2, subfamily E and polypeptide 1 (CYP2E1) polymorphisms with KD. METHODS: We selected 6 tag single-nucleotide polymorphisms (SNPs) of the CYP2E1 gene for TaqMan allelic discrimination assay in 340 KD patients and performed analysis on the clinical phenotypes and coronary artery lesions (CALs). CAL associations of tag SNPs were adjusted for age and gender in the logistic regression. RESULTS: The KD patients with a CC genotype of rs915906 demonstrated a greater proportion of CAL formation (P = 0.009). Furthermore, the GG genotype frequencies of rs2070676 showed a significantly greater risk for CAL formation in KD patients (P = 0.007). However, the SNPs of the CYP2E1 gene did not influence CAL formation in the participating KD patients either with or without high-dose acetylsalicylic acid. Using the expression quantitative trait locus analyses, we found that the SNPs associated with CAL formation in KD also affected CYP2E1 expression in certain cell types. CONCLUSION: This study is the first to find that the risk of CAL formation is related to CYP2E1 gene polymorphisms in KD patients.
[Mh] Termos MeSH primário: Doença da Artéria Coronariana/epidemiologia
Doença da Artéria Coronariana/genética
Citocromo P-450 CYP2E1/genética
Síndrome de Linfonodos Mucocutâneos/epidemiologia
Síndrome de Linfonodos Mucocutâneos/genética
Polimorfismo de Nucleotídeo Único/genética
[Mh] Termos MeSH secundário: Pré-Escolar
Estudos de Coortes
Feminino
Predisposição Genética para Doença/epidemiologia
Predisposição Genética para Doença/genética
Seres Humanos
Lactente
Masculino
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 1.14.13.- (Cytochrome P-450 CYP2E1)
[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:170627
[St] Status:MEDLINE
[do] DOI:10.1097/INF.0000000000001657



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