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...
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Formato: | Articulo |
Lenguaje: | Inglés |
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2014
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Acceso en línea: | http://sedici.unlp.edu.ar/handle/10915/134852 |
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I19-R120-10915-134852 |
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institution |
Universidad Nacional de La Plata |
institution_str |
I-19 |
repository_str |
R-120 |
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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 |
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