Avaliação do efeito do 17β-estradiol sobre a expressão gênica da conexina40 e suas implicações na propagação da atividade elétrica cardíaca

Detalhes bibliográficos
Autor(a) principal: Amarante, Débora Barbosa
Data de Publicação: 2016
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UFRRJ
Texto Completo: https://rima.ufrrj.br/jspui/handle/20.500.14407/11402
Resumo: O 17β-estradiol (E2), regula muitos genes cardíacos através de seu receptor (receptor para estrógeno, RE). A propagação da atividade elétrica no miocárdio depende da transferência de corrente através das junções comunicantes. As conexinas 40 (Cx40) e 43 são as principais conexinas que formam as junções expressas no coração. Em camundongos, a Cx40 é restrita ao átrio e sistema de condução. Alterações na expressão ou atividade da Cx40 estão associadas a fibrilação atrial. Aqui nós avaliamos o efeito do E2 in vitro e in vivo sobre a expressão do RNAm da Cx40 nos átrios e correlacionamos aos estudos eletrocardiográficos (ECG). Nós tratamos a linhagem A7r5 (derivada de músculo liso aórtico de rato embrionário) com alta e baixa concentrações de benzoato de estradiol, BE, (10-6 M e 10-8 M) durante 24 horas e cultura primária de cardiomiócitos atriais de ratos neonatos foram incubados com BE 10-6 M durante 2, 4 e 8 horas. Ensaios de transfecção transiente foram realizados na linhagem A7r5 com um plasmídeo contendo um segmento da região promotora da Cx40 (-1190/+121Cx40LucpGL3) e tratadas com 10-6 M de BE durante 24 horas. Camundongos fêmeas foram ovariectomizadas (OVX) e então tratadas com baixa (2 microgramas) e alta (20 microgramas) doses de benzoato de estradiol (OVX+BE2 e OVX+BE20) durante 15 dias, sendo que o grupo controle sofreu apenas estresse cirúrgico (FO). Foram realizados registros ECG e a expressão atrial do RNAm da Cx40 foi avaliada por RT-PCR em tempo real. Nós observamos que altas doses de BE diminui a expressão do RNAm da Cx40 in vitro (na linhagem A7r5 e na cultura de cardiomiócitos). A atividade transcricional do promotor foi inibida por BE10-6 M. Nós observamos diminuição da frequência cardíaca dos animais do grupo OVX em relação ao controle, grupo FO. Nenhuma diferença foi observada na frequência cardíaca entre os grupos OVX+BE2 e OVX+BE20. Os animais do grupo OVX apresentaram diminuição na duração da onda P em relação ao grupo FO, no entanto nenhuma diferença foi observada na duração da onda P entre os outros grupos. Nenhuma diferença foi observada nos outros intervalos eletrocardiográficos entre os grupos experimentais. A expressão atrial do RNAm da Cx40 estava reduzida nos animais do grupo OVX+BE20 em relação ao grupo FO. Nossos dados demonstram que altas doses de benzoato de estradiol reduzem a expressão do RNAm da Cx40 in vitro e em camundongos ovariectomizados. Nós propomos que altas doses de E2 ativa o seu receptor, e o complexo RE-E2 age diretamente no DNA, inibindo a atividade transcricional do promotor da Cx40
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spelling Amarante, Débora BarbosaAlmeida, Norma Aparecida dos Santos7234019774http://lattes.cnpq.br/8601494649709728Fortes, Fabio da Silva de AzevedoOliveira, Elaine de5516345618http://lattes.cnpq.br/89692602032966972023-12-22T01:52:18Z2023-12-22T01:52:18Z2016-02-26AMARANTE, D. B. Avaliação do efeito do 17β-estradiol sobre a expressão gênica da conexina40 e suas implicações na propagação da atividade elétrica cardíaca. 2016. 48 f. Dissertação (Mestrado em Ciências Fisiológica) - Instituto de Ciências Biológicas e da Saúde - Universidade Federal Rural do Rio de Janeiro, Seropédica-RJ, 2016 .https://rima.ufrrj.br/jspui/handle/20.500.14407/11402O 17β-estradiol (E2), regula muitos genes cardíacos através de seu receptor (receptor para estrógeno, RE). A propagação da atividade elétrica no miocárdio depende da transferência de corrente através das junções comunicantes. As conexinas 40 (Cx40) e 43 são as principais conexinas que formam as junções expressas no coração. Em camundongos, a Cx40 é restrita ao átrio e sistema de condução. Alterações na expressão ou atividade da Cx40 estão associadas a fibrilação atrial. Aqui nós avaliamos o efeito do E2 in vitro e in vivo sobre a expressão do RNAm da Cx40 nos átrios e correlacionamos aos estudos eletrocardiográficos (ECG). Nós tratamos a linhagem A7r5 (derivada de músculo liso aórtico de rato embrionário) com alta e baixa concentrações de benzoato de estradiol, BE, (10-6 M e 10-8 M) durante 24 horas e cultura primária de cardiomiócitos atriais de ratos neonatos foram incubados com BE 10-6 M durante 2, 4 e 8 horas. Ensaios de transfecção transiente foram realizados na linhagem A7r5 com um plasmídeo contendo um segmento da região promotora da Cx40 (-1190/+121Cx40LucpGL3) e tratadas com 10-6 M de BE durante 24 horas. Camundongos fêmeas foram ovariectomizadas (OVX) e então tratadas com baixa (2 microgramas) e alta (20 microgramas) doses de benzoato de estradiol (OVX+BE2 e OVX+BE20) durante 15 dias, sendo que o grupo controle sofreu apenas estresse cirúrgico (FO). Foram realizados registros ECG e a expressão atrial do RNAm da Cx40 foi avaliada por RT-PCR em tempo real. Nós observamos que altas doses de BE diminui a expressão do RNAm da Cx40 in vitro (na linhagem A7r5 e na cultura de cardiomiócitos). A atividade transcricional do promotor foi inibida por BE10-6 M. Nós observamos diminuição da frequência cardíaca dos animais do grupo OVX em relação ao controle, grupo FO. Nenhuma diferença foi observada na frequência cardíaca entre os grupos OVX+BE2 e OVX+BE20. Os animais do grupo OVX apresentaram diminuição na duração da onda P em relação ao grupo FO, no entanto nenhuma diferença foi observada na duração da onda P entre os outros grupos. Nenhuma diferença foi observada nos outros intervalos eletrocardiográficos entre os grupos experimentais. A expressão atrial do RNAm da Cx40 estava reduzida nos animais do grupo OVX+BE20 em relação ao grupo FO. Nossos dados demonstram que altas doses de benzoato de estradiol reduzem a expressão do RNAm da Cx40 in vitro e em camundongos ovariectomizados. Nós propomos que altas doses de E2 ativa o seu receptor, e o complexo RE-E2 age diretamente no DNA, inibindo a atividade transcricional do promotor da Cx40Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESThe 17β-estradiol (E2) regulate many cardiac genes via its estrogen receptor (ER). The propagation of electrical activity in the myocardium depends on the current transfer at gap junctions. Connexins 40 (Cx40) and 43 are the predominant junctional proteins. In mice, Cx40 is restricted to the atrium and conduction system. Alterations of Cx40 expression or activity are associated with atrial fibrillation. Here we evaluate the effect of the E2 onCx40 mRNA expression, in vitro, and in vivo the effect on atrium expression of Cx40 mRNA in correlation to ECG studies. We treated A7r5 cells (smooth muscle cells from rat thoracic aorta) with low and high doses ofestradiol benzoate, EB, (10-8 M and 10-6M) for 24h and rat neonatal cardiomyocytes with EB 10-6 M for 2, 4 and8 hours. A7r5 cells were trasiently transfected with 0.5 microgramas of the test plasmid (-1190/+121Cx40Luc pGL3) and treated with 10-6M of EB for 24 hours. Female mice were subjected to ovariectomy (OVX) and then, treated with a low (2g) and a high dose (20g) of estradiol benzoate (EB; OVX+EB2 and OVX+EB20) for 15 days. ECG recordings were obtained from mice and atrium Cx40 mRNA expression were evaluated by RT-PCR real time. First, we observed that high doses of EB down regulated Cx40 mRNA in vitro (A7r5 cells and rat atrial cardiomyocytes). The transcriptional activity of Cx40 promoter was inhibited by 10-6M of EB in A7r5 cells. We observed lower heart rate for OVX animals when to compared to control animals, FO. In this regard, no difference was observed between OVX+EB2 and OVX+BE20 heart rate. The OVX group showed decrease P wave duration when to compared to FO group, but no difference in the P wave duration was observed among the others groups. No difference was observed in another ECG intervals among the experimental groups. The atrial Cx40mRNA level was reduced in OVX+BE20group when to compared to FO group. Our data indicate, for the first time, high doses of estradiol benzoate reduce Cx40 mRNA in vitro and ovariectomized mice. 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dc.title.por.fl_str_mv Avaliação do efeito do 17β-estradiol sobre a expressão gênica da conexina40 e suas implicações na propagação da atividade elétrica cardíaca
dc.title.alternative.eng.fl_str_mv Evaluation of the effect of 17 β-estradiol on the gene expression of Connexin40 and its implications for the spread of cardiac electrical activity.
title Avaliação do efeito do 17β-estradiol sobre a expressão gênica da conexina40 e suas implicações na propagação da atividade elétrica cardíaca
spellingShingle Avaliação do efeito do 17β-estradiol sobre a expressão gênica da conexina40 e suas implicações na propagação da atividade elétrica cardíaca
Amarante, Débora Barbosa
Connexin40 mRNA
estradiol benzoate
RNAm da Conexina40
benzoato de estradiol
ECG
coração e camundongo
ECG
heart and mouse
Fisiologia
title_short Avaliação do efeito do 17β-estradiol sobre a expressão gênica da conexina40 e suas implicações na propagação da atividade elétrica cardíaca
title_full Avaliação do efeito do 17β-estradiol sobre a expressão gênica da conexina40 e suas implicações na propagação da atividade elétrica cardíaca
title_fullStr Avaliação do efeito do 17β-estradiol sobre a expressão gênica da conexina40 e suas implicações na propagação da atividade elétrica cardíaca
title_full_unstemmed Avaliação do efeito do 17β-estradiol sobre a expressão gênica da conexina40 e suas implicações na propagação da atividade elétrica cardíaca
title_sort Avaliação do efeito do 17β-estradiol sobre a expressão gênica da conexina40 e suas implicações na propagação da atividade elétrica cardíaca
author Amarante, Débora Barbosa
author_facet Amarante, Débora Barbosa
author_role author
dc.contributor.author.fl_str_mv Amarante, Débora Barbosa
dc.contributor.advisor1.fl_str_mv Almeida, Norma Aparecida dos Santos
dc.contributor.advisor1ID.fl_str_mv 7234019774
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/8601494649709728
dc.contributor.referee1.fl_str_mv Fortes, Fabio da Silva de Azevedo
dc.contributor.referee2.fl_str_mv Oliveira, Elaine de
dc.contributor.authorID.fl_str_mv 5516345618
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/8969260203296697
contributor_str_mv Almeida, Norma Aparecida dos Santos
Fortes, Fabio da Silva de Azevedo
Oliveira, Elaine de
dc.subject.eng.fl_str_mv Connexin40 mRNA
estradiol benzoate
topic Connexin40 mRNA
estradiol benzoate
RNAm da Conexina40
benzoato de estradiol
ECG
coração e camundongo
ECG
heart and mouse
Fisiologia
dc.subject.por.fl_str_mv RNAm da Conexina40
benzoato de estradiol
ECG
coração e camundongo
ECG
heart and mouse
dc.subject.cnpq.fl_str_mv Fisiologia
description O 17β-estradiol (E2), regula muitos genes cardíacos através de seu receptor (receptor para estrógeno, RE). A propagação da atividade elétrica no miocárdio depende da transferência de corrente através das junções comunicantes. As conexinas 40 (Cx40) e 43 são as principais conexinas que formam as junções expressas no coração. Em camundongos, a Cx40 é restrita ao átrio e sistema de condução. Alterações na expressão ou atividade da Cx40 estão associadas a fibrilação atrial. Aqui nós avaliamos o efeito do E2 in vitro e in vivo sobre a expressão do RNAm da Cx40 nos átrios e correlacionamos aos estudos eletrocardiográficos (ECG). Nós tratamos a linhagem A7r5 (derivada de músculo liso aórtico de rato embrionário) com alta e baixa concentrações de benzoato de estradiol, BE, (10-6 M e 10-8 M) durante 24 horas e cultura primária de cardiomiócitos atriais de ratos neonatos foram incubados com BE 10-6 M durante 2, 4 e 8 horas. Ensaios de transfecção transiente foram realizados na linhagem A7r5 com um plasmídeo contendo um segmento da região promotora da Cx40 (-1190/+121Cx40LucpGL3) e tratadas com 10-6 M de BE durante 24 horas. Camundongos fêmeas foram ovariectomizadas (OVX) e então tratadas com baixa (2 microgramas) e alta (20 microgramas) doses de benzoato de estradiol (OVX+BE2 e OVX+BE20) durante 15 dias, sendo que o grupo controle sofreu apenas estresse cirúrgico (FO). Foram realizados registros ECG e a expressão atrial do RNAm da Cx40 foi avaliada por RT-PCR em tempo real. Nós observamos que altas doses de BE diminui a expressão do RNAm da Cx40 in vitro (na linhagem A7r5 e na cultura de cardiomiócitos). A atividade transcricional do promotor foi inibida por BE10-6 M. Nós observamos diminuição da frequência cardíaca dos animais do grupo OVX em relação ao controle, grupo FO. Nenhuma diferença foi observada na frequência cardíaca entre os grupos OVX+BE2 e OVX+BE20. Os animais do grupo OVX apresentaram diminuição na duração da onda P em relação ao grupo FO, no entanto nenhuma diferença foi observada na duração da onda P entre os outros grupos. Nenhuma diferença foi observada nos outros intervalos eletrocardiográficos entre os grupos experimentais. A expressão atrial do RNAm da Cx40 estava reduzida nos animais do grupo OVX+BE20 em relação ao grupo FO. Nossos dados demonstram que altas doses de benzoato de estradiol reduzem a expressão do RNAm da Cx40 in vitro e em camundongos ovariectomizados. Nós propomos que altas doses de E2 ativa o seu receptor, e o complexo RE-E2 age diretamente no DNA, inibindo a atividade transcricional do promotor da Cx40
publishDate 2016
dc.date.issued.fl_str_mv 2016-02-26
dc.date.accessioned.fl_str_mv 2023-12-22T01:52:18Z
dc.date.available.fl_str_mv 2023-12-22T01:52:18Z
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.citation.fl_str_mv AMARANTE, D. B. Avaliação do efeito do 17β-estradiol sobre a expressão gênica da conexina40 e suas implicações na propagação da atividade elétrica cardíaca. 2016. 48 f. Dissertação (Mestrado em Ciências Fisiológica) - Instituto de Ciências Biológicas e da Saúde - Universidade Federal Rural do Rio de Janeiro, Seropédica-RJ, 2016 .
dc.identifier.uri.fl_str_mv https://rima.ufrrj.br/jspui/handle/20.500.14407/11402
identifier_str_mv AMARANTE, D. B. Avaliação do efeito do 17β-estradiol sobre a expressão gênica da conexina40 e suas implicações na propagação da atividade elétrica cardíaca. 2016. 48 f. Dissertação (Mestrado em Ciências Fisiológica) - Instituto de Ciências Biológicas e da Saúde - Universidade Federal Rural do Rio de Janeiro, Seropédica-RJ, 2016 .
url https://rima.ufrrj.br/jspui/handle/20.500.14407/11402
dc.language.iso.fl_str_mv por
language por
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