Expressão de Nrf2 e NFkB em pacientes renais crônicos em hemodiálise
Autor(a) principal: | |
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Data de Publicação: | 2013 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional da Universidade Federal Fluminense (RIUFF) |
Texto Completo: | https://app.uff.br/riuff/handle/1/20459 |
Resumo: | Oxidative stress and inflammation, important cardiovascular risk factors, are common features of patients with chronic kidney disease (CKD). Nuclear transcription factors are involved in these processes as NFB which plays important role in the coordinate expression of inflammatory genes in these patients and the Keap1-Nrf2, which unlike NFB operates in the genes promoter region coding for detoxifying enzymes stage II or antioxidant enzymes such as heme oxygenase 1 (HO-1) and NADPH quinone oxidoreductase 1 (NQO1). The latter has emerged as important endogenous defense mechanism, incombat inflammation as well as oxidative stress, which may contribute to the improvement of cardiovascular complications of many diseases, including CKD. However, no study has evaluated to date this transcriptional factor in patients with CKD. The objective of this study was to evaluate the expression of Nfr2 and NFB in patients on hemodialysis (HD). Twenty HD patients (55.0 ± 15.2 years, time of dialysis 76.5 ± 46.3 months, BMI 23.6 ± 3.0 kg/m2) were compared with 11 healthy subjects (50.9 ± 8.0 years, BMI 23.8 ± 1.9 kg/m2). Malondialdehyde (MDA) was measured by reaction with thiobarbituric acid. Peripheral blood mononuclear cells were isolated and analysis of real-time polymerase chain reaction was performed to evaluate mRNA levels of Nrf2, NFB, NQO1 and HO-1. MDA levels were significantly higher in HD patients compared to the control group (13.2 ± 5.3 nmol/mL vs 5.1 ± 2.7 nmol/mL, p <0.01). The Nrf2 expression was lower in patients compared to healthy subjects (0.58 ± 0.35 vs 1.13 ± 0.64, p = 0.005). In contrast, the expression of NFB was higher in this patients (2.18 ± 0.8 vs 1.04 ± 0.22, p = 0.0001). In addition, patients showed reduced expression of mRNA for NQO1 compared to healthy individuals. There was no difference in HO-1 expression. In patients, Nrf2 was negatively correlated with NFB (r = -0.54, p = 0.014) and positive in healthy individuals (r = 0.77, p = 0.006). In conclusion, kidney patients on HD showed increased expression of NFB and reduced expression of Nrf2 and NQO1, showing there is a possible imbalance in the transcriptional regulation of NFB/Nrf2 in CKD patients on HD, which could increase the oxidative stress and inflammation in these patients |
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Expressão de Nrf2 e NFkB em pacientes renais crônicos em hemodiáliseExpression of Nrf2 and NFkB in patients on hemodialysisNrf2NFkBInflamaçãoEstresse OxidativoHemodiáliseMEDICINACIÊNCIAS CARDIOVASCULARESInsuficiência renalEstresseNrf2NFkBInflammationOxidative StressHemodialysisCNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA::CARDIOLOGIAOxidative stress and inflammation, important cardiovascular risk factors, are common features of patients with chronic kidney disease (CKD). Nuclear transcription factors are involved in these processes as NFB which plays important role in the coordinate expression of inflammatory genes in these patients and the Keap1-Nrf2, which unlike NFB operates in the genes promoter region coding for detoxifying enzymes stage II or antioxidant enzymes such as heme oxygenase 1 (HO-1) and NADPH quinone oxidoreductase 1 (NQO1). The latter has emerged as important endogenous defense mechanism, incombat inflammation as well as oxidative stress, which may contribute to the improvement of cardiovascular complications of many diseases, including CKD. However, no study has evaluated to date this transcriptional factor in patients with CKD. The objective of this study was to evaluate the expression of Nfr2 and NFB in patients on hemodialysis (HD). Twenty HD patients (55.0 ± 15.2 years, time of dialysis 76.5 ± 46.3 months, BMI 23.6 ± 3.0 kg/m2) were compared with 11 healthy subjects (50.9 ± 8.0 years, BMI 23.8 ± 1.9 kg/m2). Malondialdehyde (MDA) was measured by reaction with thiobarbituric acid. Peripheral blood mononuclear cells were isolated and analysis of real-time polymerase chain reaction was performed to evaluate mRNA levels of Nrf2, NFB, NQO1 and HO-1. MDA levels were significantly higher in HD patients compared to the control group (13.2 ± 5.3 nmol/mL vs 5.1 ± 2.7 nmol/mL, p <0.01). The Nrf2 expression was lower in patients compared to healthy subjects (0.58 ± 0.35 vs 1.13 ± 0.64, p = 0.005). In contrast, the expression of NFB was higher in this patients (2.18 ± 0.8 vs 1.04 ± 0.22, p = 0.0001). In addition, patients showed reduced expression of mRNA for NQO1 compared to healthy individuals. There was no difference in HO-1 expression. In patients, Nrf2 was negatively correlated with NFB (r = -0.54, p = 0.014) and positive in healthy individuals (r = 0.77, p = 0.006). In conclusion, kidney patients on HD showed increased expression of NFB and reduced expression of Nrf2 and NQO1, showing there is a possible imbalance in the transcriptional regulation of NFB/Nrf2 in CKD patients on HD, which could increase the oxidative stress and inflammation in these patientsO estresse oxidativo e a inflamação, importantes fatores de risco cardiovascular, são características comuns de pacientes com doença renal crônica (DRC). Fatores de transcrição nucleares estão envolvidos nesses processos, como o NFB que desempenha papel importante na expressão coordenada de genes inflamatórios nesses pacientes e o Keap1-Nrf2, que ao contrário de NFB atua na região promotora dos genes que codificam enzimas desintoxicantes de fase II ou enzimas antioxidantes, como heme oxigenase 1 (HO-1) e NADPH quinona oxidoreductase 1 (NQO1). Este último tem surgido como importante mecanismo de defesa endógena, tanto no combate à inflamação como no estresse oxidativo, podendo contribuir para a melhoria das complicações cardiovasculares de muitas doenças, incluindo a DRC. No entanto, nenhum trabalho avaliou até o presente momento esse fator transcricional em pacientes com DRC. Assim, o objetivo deste trabalho foi avaliar a expressão de Nfr2 e NFB em pacientes renais crônicos em hemodiálise (HD). Vinte pacientes em tratamento de HD (55,0 ± 15,2 anos, tempo de diálise de 76,5 ± 46,3 meses, IMC 23,6 ± 3,0 kg/m2) foram comparados com 11 indivíduos saudáveis (50,9 ± 8,0 anos, IMC 23,8 ± 1,9 kg/m2). Malondialdeído (MDA) foi medido pela reação com o ácido tiobarbitúrico. Células mononucleares do sangue periférico foram isoladas e análise de reação em cadeia de polimerase em tempo real foi realizada para avaliar os níveis de mRNA de Nrf2, NFB, NQO1 e HO-1. Os níveis de MDA foram significativamente maiores nos pacientes em HD quando comparados ao grupo controle (13,2 ± 5,3 nmol/mL vs 5,1 ± 2,7 nmol/mL; p<0,01). A expressão de Nrf2 foi menor nos pacientes em relação aos indivíduos saudáveis (0,58 ± 0,35 vs 1,13 ± 0,64; p=0,005). Em contrapartida, a expressão de NFB foi maior nos pacientes (2,18 ± 0,8 vs 1,04 ± 0,22; p = 0,0001). Além disso, os pacientes mostraram reduzida expressão de mRNA para NQO1 quando comparados com os indivíduos saudáveis. Não houve diferença nos valores de HO-1. Nos pacientes, Nrf2 foi negativamente correlacionada com NFB (r = -0,54; p = 0,014) e positiva nos indivíduos saudáveis (r = 0,77; p = 0,006). Em conclusão, os pacientes renais em HD apresentaram aumentada expressão de NFB e reduzida expressão de Nrf2 e NQO1, mostrando haver um possível desequilíbrio na regulação transcricional de NFB/Nrf2 em pacientes com DRC em HD, o que contribuiria para o aumento do estresse oxidativo e inflamação nesses pacientesPrograma de Pós-graduação em CardiologiaCardiologiaMafra, DeniseCPF:98795748422http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4701421A2Cardozo, Ludmila Ferreira Medeiros de FrançaCPF:85947107722http://lattes.cnpq.br/2547887546741044Lobo, Julie CalixtoCPF:94749185222http://lattes.cnpq.br/8131918390177590Eduardo, José Carlos CarraroCPF:79681819222http://lattes.cnpq.br/1387680834725015Pinto, Milena Barcza StocklerCPF:85952864722http://lattes.cnpq.br/4659615437859275Pedruzzi, Liliana Magnago2021-03-10T20:50:17Z2014-02-242021-03-10T20:50:17Z2013-12-09info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttps://app.uff.br/riuff/handle/1/20459porCC-BY-SAinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da Universidade Federal Fluminense (RIUFF)instname:Universidade Federal Fluminense (UFF)instacron:UFF2021-03-10T20:50:17Zoai:app.uff.br:1/20459Repositório InstitucionalPUBhttps://app.uff.br/oai/requestriuff@id.uff.bropendoar:21202021-03-10T20:50:17Repositório Institucional da Universidade Federal Fluminense (RIUFF) - Universidade Federal Fluminense (UFF)false |
dc.title.none.fl_str_mv |
Expressão de Nrf2 e NFkB em pacientes renais crônicos em hemodiálise Expression of Nrf2 and NFkB in patients on hemodialysis |
title |
Expressão de Nrf2 e NFkB em pacientes renais crônicos em hemodiálise |
spellingShingle |
Expressão de Nrf2 e NFkB em pacientes renais crônicos em hemodiálise Pedruzzi, Liliana Magnago Nrf2 NFkB Inflamação Estresse Oxidativo Hemodiálise MEDICINA CIÊNCIAS CARDIOVASCULARES Insuficiência renal Estresse Nrf2 NFkB Inflammation Oxidative Stress Hemodialysis CNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA::CARDIOLOGIA |
title_short |
Expressão de Nrf2 e NFkB em pacientes renais crônicos em hemodiálise |
title_full |
Expressão de Nrf2 e NFkB em pacientes renais crônicos em hemodiálise |
title_fullStr |
Expressão de Nrf2 e NFkB em pacientes renais crônicos em hemodiálise |
title_full_unstemmed |
Expressão de Nrf2 e NFkB em pacientes renais crônicos em hemodiálise |
title_sort |
Expressão de Nrf2 e NFkB em pacientes renais crônicos em hemodiálise |
author |
Pedruzzi, Liliana Magnago |
author_facet |
Pedruzzi, Liliana Magnago |
author_role |
author |
dc.contributor.none.fl_str_mv |
Mafra, Denise CPF:98795748422 http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4701421A2 Cardozo, Ludmila Ferreira Medeiros de França CPF:85947107722 http://lattes.cnpq.br/2547887546741044 Lobo, Julie Calixto CPF:94749185222 http://lattes.cnpq.br/8131918390177590 Eduardo, José Carlos Carraro CPF:79681819222 http://lattes.cnpq.br/1387680834725015 Pinto, Milena Barcza Stockler CPF:85952864722 http://lattes.cnpq.br/4659615437859275 |
dc.contributor.author.fl_str_mv |
Pedruzzi, Liliana Magnago |
dc.subject.por.fl_str_mv |
Nrf2 NFkB Inflamação Estresse Oxidativo Hemodiálise MEDICINA CIÊNCIAS CARDIOVASCULARES Insuficiência renal Estresse Nrf2 NFkB Inflammation Oxidative Stress Hemodialysis CNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA::CARDIOLOGIA |
topic |
Nrf2 NFkB Inflamação Estresse Oxidativo Hemodiálise MEDICINA CIÊNCIAS CARDIOVASCULARES Insuficiência renal Estresse Nrf2 NFkB Inflammation Oxidative Stress Hemodialysis CNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA::CARDIOLOGIA |
description |
Oxidative stress and inflammation, important cardiovascular risk factors, are common features of patients with chronic kidney disease (CKD). Nuclear transcription factors are involved in these processes as NFB which plays important role in the coordinate expression of inflammatory genes in these patients and the Keap1-Nrf2, which unlike NFB operates in the genes promoter region coding for detoxifying enzymes stage II or antioxidant enzymes such as heme oxygenase 1 (HO-1) and NADPH quinone oxidoreductase 1 (NQO1). The latter has emerged as important endogenous defense mechanism, incombat inflammation as well as oxidative stress, which may contribute to the improvement of cardiovascular complications of many diseases, including CKD. However, no study has evaluated to date this transcriptional factor in patients with CKD. The objective of this study was to evaluate the expression of Nfr2 and NFB in patients on hemodialysis (HD). Twenty HD patients (55.0 ± 15.2 years, time of dialysis 76.5 ± 46.3 months, BMI 23.6 ± 3.0 kg/m2) were compared with 11 healthy subjects (50.9 ± 8.0 years, BMI 23.8 ± 1.9 kg/m2). Malondialdehyde (MDA) was measured by reaction with thiobarbituric acid. Peripheral blood mononuclear cells were isolated and analysis of real-time polymerase chain reaction was performed to evaluate mRNA levels of Nrf2, NFB, NQO1 and HO-1. MDA levels were significantly higher in HD patients compared to the control group (13.2 ± 5.3 nmol/mL vs 5.1 ± 2.7 nmol/mL, p <0.01). The Nrf2 expression was lower in patients compared to healthy subjects (0.58 ± 0.35 vs 1.13 ± 0.64, p = 0.005). In contrast, the expression of NFB was higher in this patients (2.18 ± 0.8 vs 1.04 ± 0.22, p = 0.0001). In addition, patients showed reduced expression of mRNA for NQO1 compared to healthy individuals. There was no difference in HO-1 expression. In patients, Nrf2 was negatively correlated with NFB (r = -0.54, p = 0.014) and positive in healthy individuals (r = 0.77, p = 0.006). In conclusion, kidney patients on HD showed increased expression of NFB and reduced expression of Nrf2 and NQO1, showing there is a possible imbalance in the transcriptional regulation of NFB/Nrf2 in CKD patients on HD, which could increase the oxidative stress and inflammation in these patients |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013-12-09 2014-02-24 2021-03-10T20:50:17Z 2021-03-10T20:50:17Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://app.uff.br/riuff/handle/1/20459 |
url |
https://app.uff.br/riuff/handle/1/20459 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
CC-BY-SA info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
CC-BY-SA |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Programa de Pós-graduação em Cardiologia Cardiologia |
publisher.none.fl_str_mv |
Programa de Pós-graduação em Cardiologia Cardiologia |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da Universidade Federal Fluminense (RIUFF) instname:Universidade Federal Fluminense (UFF) instacron:UFF |
instname_str |
Universidade Federal Fluminense (UFF) |
instacron_str |
UFF |
institution |
UFF |
reponame_str |
Repositório Institucional da Universidade Federal Fluminense (RIUFF) |
collection |
Repositório Institucional da Universidade Federal Fluminense (RIUFF) |
repository.name.fl_str_mv |
Repositório Institucional da Universidade Federal Fluminense (RIUFF) - Universidade Federal Fluminense (UFF) |
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riuff@id.uff.br |
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1802135329830862848 |