Avalia??o do efeito do 17?-estradiol sobre a express?o g?nica da conexina40 e suas implica??es na propaga??o da atividade el?trica card?aca

Detalhes bibliográficos
Ano de defesa: 2016
Autor(a) principal: Amarante, D?bora Barbosa lattes
Orientador(a): Almeida, Norma Aparecida dos Santos lattes
Banca de defesa: Fortes, Fabio da Silva de Azevedo, Oliveira, Elaine de
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Federal Rural do Rio de Janeiro
Programa de Pós-Graduação: Programa de P?s-Gradua??o em Ci?ncias Fisiol?gicas
Departamento: Instituto de Ci?ncias Biol?gicas e da Sa?de
País: Brasil
Palavras-chave em Português:
ECG
Palavras-chave em Inglês:
Área do conhecimento CNPq:
Link de acesso: https://tede.ufrrj.br/jspui/handle/jspui/1394
Resumo: The 17?-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. We proposed that when E2 levels are high, the complex ER-E2 acts directly from the DNA, inhibiting the transcriptional activity of Cx40 promoter
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spelling Almeida, Norma Aparecida dos Santos7234019774http://lattes.cnpq.br/8601494649709728Fortes, Fabio da Silva de AzevedoOliveira, Elaine de5516345618http://lattes.cnpq.br/8969260203296697Amarante, D?bora Barbosa2017-01-26T11:36:13Z2016-02-26AMARANTE, D. B. Avalia??o do efeito do 17?-estradiol sobre a express?o g?nica da conexina40 e suas implica??es na propaga??o da atividade el?trica card?aca. 2016. 48 f. Disserta??o (Mestrado em Ci?ncias Fisiol?gica) - Instituto de Ci?ncias Biol?gicas e da Sa?de - Universidade Federal Rural do Rio de Janeiro, Serop?dica-RJ, 2016 .https://tede.ufrrj.br/jspui/handle/jspui/1394The 17?-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. We proposed that when E2 levels are high, the complex ER-E2 acts directly from the DNA, inhibiting the transcriptional activity of Cx40 promoterO 17?-estradiol (E2), regula muitos genes card?acos atrav?s de seu receptor (receptor para estr?geno, RE). A propaga??o da atividade el?trica no mioc?rdio depende da transfer?ncia de corrente atrav?s das jun??es comunicantes. As conexinas 40 (Cx40) e 43 s?o as principais conexinas que formam as jun??es expressas no cora??o. Em camundongos, a Cx40 ? restrita ao ?trio e sistema de condu??o. Altera??es na express?o ou atividade da Cx40 est?o associadas a fibrila??o atrial. Aqui n?s avaliamos o efeito do E2 in vitro e in vivo sobre a express?o do RNAm da Cx40 nos ?trios e correlacionamos aos estudos eletrocardiogr?ficos (ECG). N?s tratamos a linhagem A7r5 (derivada de m?sculo liso a?rtico de rato embrion?rio) com alta e baixa concentra??es de benzoato de estradiol, BE, (10-6 M e 10-8 M) durante 24 horas e cultura prim?ria de cardiomi?citos atriais de ratos neonatos foram incubados com BE 10-6 M durante 2, 4 e 8 horas. Ensaios de transfec??o transiente foram realizados na linhagem A7r5 com um plasm?deo contendo um segmento da regi?o promotora da Cx40 (-1190/+121Cx40LucpGL3) e tratadas com 10-6 M de BE durante 24 horas. Camundongos f?meas foram ovariectomizadas (OVX) e ent?o 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 cir?rgico (FO). Foram realizados registros ECG e a express?o atrial do RNAm da Cx40 foi avaliada por RT-PCR em tempo real. N?s observamos que altas doses de BE diminui a express?o do RNAm da Cx40 in vitro (na linhagem A7r5 e na cultura de cardiomi?citos). A atividade transcricional do promotor foi inibida por BE10-6 M. N?s observamos diminui??o da frequ?ncia card?aca dos animais do grupo OVX em rela??o ao controle, grupo FO. Nenhuma diferen?a foi observada na frequ?ncia card?aca entre os grupos OVX+BE2 e OVX+BE20. Os animais do grupo OVX apresentaram diminui??o na dura??o da onda P em rela??o ao grupo FO, no entanto nenhuma diferen?a foi observada na dura??o da onda P entre os outros grupos. Nenhuma diferen?a foi observada nos outros intervalos eletrocardiogr?ficos entre os grupos experimentais. A express?o atrial do RNAm da Cx40 estava reduzida nos animais do grupo OVX+BE20 em rela??o ao grupo FO. Nossos dados demonstram que altas doses de benzoato de estradiol reduzem a express?o do RNAm da Cx40 in vitro e em camundongos ovariectomizados. N?s 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 Cx40Submitted by Sandra Pereira (srpereira@ufrrj.br) on 2017-01-26T11:36:13Z No. of bitstreams: 1 2016 - D?bora Barbosa Amarante.pdf: 1603287 bytes, checksum: 8c473e3225022499b4e4dc93119df63f (MD5)Made available in DSpace on 2017-01-26T11:36:13Z (GMT). No. of bitstreams: 1 2016 - D?bora Barbosa Amarante.pdf: 1603287 bytes, checksum: 8c473e3225022499b4e4dc93119df63f (MD5) Previous issue date: 2016-02-26Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPESapplication/pdfhttps://tede.ufrrj.br/retrieve/5055/2016%20-%20D%c3%a9bora%20Barbosa%20Amarante.pdf.jpghttps://tede.ufrrj.br/retrieve/19696/2016%20-%20D%c3%a9bora%20Barbosa%20Amarante.pdf.jpghttps://tede.ufrrj.br/retrieve/26039/2016%20-%20D%c3%a9bora%20Barbosa%20Amarante.pdf.jpghttps://tede.ufrrj.br/retrieve/32472/2016%20-%20D%c3%a9bora%20Barbosa%20Amarante.pdf.jpghttps://tede.ufrrj.br/retrieve/38848/2016%20-%20D%c3%a9bora%20Barbosa%20Amarante.pdf.jpghttps://tede.ufrrj.br/retrieve/45262/2016%20-%20D%c3%a9bora%20Barbosa%20Amarante.pdf.jpghttps://tede.ufrrj.br/retrieve/51640/2016%20-%20D%c3%a9bora%20Barbosa%20Amarante.pdf.jpghttps://tede.ufrrj.br/retrieve/58102/2016%20-%20D%c3%a9bora%20Barbosa%20Amarante.pdf.jpgporUniversidade Federal Rural do Rio de JaneiroPrograma de P?s-Gradua??o em Ci?ncias Fisiol?gicasUFRRJBrasilInstituto de Ci?ncias Biol?gicas e da Sa?deACCONCIA, FILIPPO; MARINO, MARIA. 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dc.title.por.fl_str_mv Avalia??o do efeito do 17?-estradiol sobre a express?o g?nica da conexina40 e suas implica??es na propaga??o da atividade el?trica card?aca
dc.title.alternative.eng.fl_str_mv Evaluation of the effect of 17 ?-estradiol on the gene expression of Connexin40 and its implications for the spread of cardiac electrical activity.
title Avalia??o do efeito do 17?-estradiol sobre a express?o g?nica da conexina40 e suas implica??es na propaga??o da atividade el?trica card?aca
spellingShingle Avalia??o do efeito do 17?-estradiol sobre a express?o g?nica da conexina40 e suas implica??es na propaga??o da atividade el?trica card?aca
Amarante, D?bora Barbosa
Connexin40 mRNA
estradiol benzoate
RNAm da Conexina40
benzoato de estradiol
ECG
cora??o e camundongo
ECG
heart and mouse
Fisiologia
title_short Avalia??o do efeito do 17?-estradiol sobre a express?o g?nica da conexina40 e suas implica??es na propaga??o da atividade el?trica card?aca
title_full Avalia??o do efeito do 17?-estradiol sobre a express?o g?nica da conexina40 e suas implica??es na propaga??o da atividade el?trica card?aca
title_fullStr Avalia??o do efeito do 17?-estradiol sobre a express?o g?nica da conexina40 e suas implica??es na propaga??o da atividade el?trica card?aca
title_full_unstemmed Avalia??o do efeito do 17?-estradiol sobre a express?o g?nica da conexina40 e suas implica??es na propaga??o da atividade el?trica card?aca
title_sort Avalia??o do efeito do 17?-estradiol sobre a express?o g?nica da conexina40 e suas implica??es na propaga??o da atividade el?trica card?aca
author Amarante, D?bora Barbosa
author_facet Amarante, D?bora Barbosa
author_role author
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
dc.contributor.author.fl_str_mv Amarante, D?bora Barbosa
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
cora??o e camundongo
ECG
heart and mouse
Fisiologia
dc.subject.por.fl_str_mv RNAm da Conexina40
benzoato de estradiol
ECG
cora??o e camundongo
ECG
heart and mouse
dc.subject.cnpq.fl_str_mv Fisiologia
description The 17?-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. We proposed that when E2 levels are high, the complex ER-E2 acts directly from the DNA, inhibiting the transcriptional activity of Cx40 promoter
publishDate 2016
dc.date.issued.fl_str_mv 2016-02-26
dc.date.accessioned.fl_str_mv 2017-01-26T11:36:13Z
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. Avalia??o do efeito do 17?-estradiol sobre a express?o g?nica da conexina40 e suas implica??es na propaga??o da atividade el?trica card?aca. 2016. 48 f. Disserta??o (Mestrado em Ci?ncias Fisiol?gica) - Instituto de Ci?ncias Biol?gicas e da Sa?de - Universidade Federal Rural do Rio de Janeiro, Serop?dica-RJ, 2016 .
dc.identifier.uri.fl_str_mv https://tede.ufrrj.br/jspui/handle/jspui/1394
identifier_str_mv AMARANTE, D. B. Avalia??o do efeito do 17?-estradiol sobre a express?o g?nica da conexina40 e suas implica??es na propaga??o da atividade el?trica card?aca. 2016. 48 f. Disserta??o (Mestrado em Ci?ncias Fisiol?gica) - Instituto de Ci?ncias Biol?gicas e da Sa?de - Universidade Federal Rural do Rio de Janeiro, Serop?dica-RJ, 2016 .
url https://tede.ufrrj.br/jspui/handle/jspui/1394
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dc.publisher.none.fl_str_mv Universidade Federal Rural do Rio de Janeiro
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