Endogenous endothelin 1 mediates angiotensin II-induced hypertrophy in electrically paced cardiac myocytes through EGFR transactivation, reactive oxygen species and NHE-1

Emerging evidence supports a key role for endothelin-1 (ET-1) and the transactivation of the epidermal growth factor receptor (EGFR) in angiotensin II (Ang II) action. We aim to determine the potential role played by endogenous ET-1, EGFR transactivation and redox-dependent sodium hydrogen exchanger...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Correa, María Verónica, Nolly, Mariela Beatriz, Caldiz, Claudia Irma, Chiappe de Cingolani, Gladys Ethel, Cingolani, Horacio Eugenio, Ennis, Irene Lucía
Formato: Articulo
Lenguaje:Inglés
Publicado: 2014
Materias:
ROS
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/134852
Aporte de:
id I19-R120-10915-134852
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Medicina
Cardiac hypertrophy
Ang II
ET-1
EGFR transactivation
NHE-1
ROS
spellingShingle Medicina
Cardiac hypertrophy
Ang II
ET-1
EGFR transactivation
NHE-1
ROS
Correa, María Verónica
Nolly, Mariela Beatriz
Caldiz, Claudia Irma
Chiappe de Cingolani, Gladys Ethel
Cingolani, Horacio Eugenio
Ennis, Irene Lucía
Endogenous endothelin 1 mediates angiotensin II-induced hypertrophy in electrically paced cardiac myocytes through EGFR transactivation, reactive oxygen species and NHE-1
topic_facet Medicina
Cardiac hypertrophy
Ang II
ET-1
EGFR transactivation
NHE-1
ROS
description Emerging evidence supports a key role for endothelin-1 (ET-1) and the transactivation of the epidermal growth factor receptor (EGFR) in angiotensin II (Ang II) action. We aim to determine the potential role played by endogenous ET-1, EGFR transactivation and redox-dependent sodium hydrogen exchanger-1 (NHE-1) activation in the hypertrophic response to Ang II of cardiac myocytes. Electrically paced adult cat cardiomyocytes were placed in culture and stimulated with 1 nmol l⁻¹ Ang II or 5 nmol l⁻¹ ET1. Ang II increased ~45 % cell surface area (CSA) and ~37 % [³H]-phenylalanine incorporation, effects that were blocked not only by losartan (Los) but also by BQ123 (AT₁ and ET<sub>A</sub> receptor antagonists, respectively). Moreover, Ang II significantly increased ET-1 messenger RNA (mRNA) expression. ET-1 similarly increased myocyte CSA and protein synthesis, actions prevented by the reactive oxygen species scavenger MPG or the NHE-1 inhibitor cariporide (carip). ET-1 increased the phosphorylation of the redox-sensitive ERK1/2- p90<sup>RSK</sup> kinases, main activators of the NHE-1. This effect was prevented by MPG and the antagonist of EGFR, AG1478. Ang II, ET-1 and EGF increased myocardial superoxide production (187±9 %, 149±8 % and 163.7±6 % of control, respectively) and AG1478 inhibited these effects. Interestingly, Los inhibited only Ang II whilst BQ123 cancelled both Ang II and ET-1 actions, supporting the sequential and unidirectional activation of AT₁, ET<sub>A</sub> and EGFR. Based on the present evidence, we propose that endogenous ET-1 mediates the hypertrophic response to Ang II by a mechanism that involves EGFR transactivation and redox-dependent activation of the ERK1/2-p90<sup>RSK</sup> and NHE-1 in adult cardiomyocytes.
format Articulo
Articulo
author Correa, María Verónica
Nolly, Mariela Beatriz
Caldiz, Claudia Irma
Chiappe de Cingolani, Gladys Ethel
Cingolani, Horacio Eugenio
Ennis, Irene Lucía
author_facet Correa, María Verónica
Nolly, Mariela Beatriz
Caldiz, Claudia Irma
Chiappe de Cingolani, Gladys Ethel
Cingolani, Horacio Eugenio
Ennis, Irene Lucía
author_sort Correa, María Verónica
title Endogenous endothelin 1 mediates angiotensin II-induced hypertrophy in electrically paced cardiac myocytes through EGFR transactivation, reactive oxygen species and NHE-1
title_short Endogenous endothelin 1 mediates angiotensin II-induced hypertrophy in electrically paced cardiac myocytes through EGFR transactivation, reactive oxygen species and NHE-1
title_full Endogenous endothelin 1 mediates angiotensin II-induced hypertrophy in electrically paced cardiac myocytes through EGFR transactivation, reactive oxygen species and NHE-1
title_fullStr Endogenous endothelin 1 mediates angiotensin II-induced hypertrophy in electrically paced cardiac myocytes through EGFR transactivation, reactive oxygen species and NHE-1
title_full_unstemmed Endogenous endothelin 1 mediates angiotensin II-induced hypertrophy in electrically paced cardiac myocytes through EGFR transactivation, reactive oxygen species and NHE-1
title_sort endogenous endothelin 1 mediates angiotensin ii-induced hypertrophy in electrically paced cardiac myocytes through egfr transactivation, reactive oxygen species and nhe-1
publishDate 2014
url http://sedici.unlp.edu.ar/handle/10915/134852
work_keys_str_mv AT correamariaveronica endogenousendothelin1mediatesangiotensiniiinducedhypertrophyinelectricallypacedcardiacmyocytesthroughegfrtransactivationreactiveoxygenspeciesandnhe1
AT nollymarielabeatriz endogenousendothelin1mediatesangiotensiniiinducedhypertrophyinelectricallypacedcardiacmyocytesthroughegfrtransactivationreactiveoxygenspeciesandnhe1
AT caldizclaudiairma endogenousendothelin1mediatesangiotensiniiinducedhypertrophyinelectricallypacedcardiacmyocytesthroughegfrtransactivationreactiveoxygenspeciesandnhe1
AT chiappedecingolanigladysethel endogenousendothelin1mediatesangiotensiniiinducedhypertrophyinelectricallypacedcardiacmyocytesthroughegfrtransactivationreactiveoxygenspeciesandnhe1
AT cingolanihoracioeugenio endogenousendothelin1mediatesangiotensiniiinducedhypertrophyinelectricallypacedcardiacmyocytesthroughegfrtransactivationreactiveoxygenspeciesandnhe1
AT ennisirenelucia endogenousendothelin1mediatesangiotensiniiinducedhypertrophyinelectricallypacedcardiacmyocytesthroughegfrtransactivationreactiveoxygenspeciesandnhe1
bdutipo_str Repositorios
_version_ 1764820455609335808