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The MEK/ERK Module Is Reprogrammed in Remodeling Adult Cardiomyocytes

Fetal and hypertrophic remodeling are hallmarks of cardiac restructuring leading chronically to heart failure. Since the Ras/Raf/MEK/ERK cascade (MAPK) is involved in the development of heart failure, we hypothesized, first, that fetal remodeling is different from hypertrophy and, second, that remod...

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Autores principales: Thomas, Kubin, Ayse, Cetinkaya, Natalia, Kubin, Peter, Bramlage, Bedriye, Sen-Hild, Praveen, Gajawada, Hakan, Akintürk, Markus, Schönburg, Wolfgang, Schaper, Yeong-Hoon, Choi, Miroslav, Barancik, Manfred, Richter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503571/
https://www.ncbi.nlm.nih.gov/pubmed/32882982
http://dx.doi.org/10.3390/ijms21176348
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author Thomas, Kubin
Ayse, Cetinkaya
Natalia, Kubin
Peter, Bramlage
Bedriye, Sen-Hild
Praveen, Gajawada
Hakan, Akintürk
Markus, Schönburg
Wolfgang, Schaper
Yeong-Hoon, Choi
Miroslav, Barancik
Manfred, Richter
author_facet Thomas, Kubin
Ayse, Cetinkaya
Natalia, Kubin
Peter, Bramlage
Bedriye, Sen-Hild
Praveen, Gajawada
Hakan, Akintürk
Markus, Schönburg
Wolfgang, Schaper
Yeong-Hoon, Choi
Miroslav, Barancik
Manfred, Richter
author_sort Thomas, Kubin
collection PubMed
description Fetal and hypertrophic remodeling are hallmarks of cardiac restructuring leading chronically to heart failure. Since the Ras/Raf/MEK/ERK cascade (MAPK) is involved in the development of heart failure, we hypothesized, first, that fetal remodeling is different from hypertrophy and, second, that remodeling of the MAPK occurs. To test our hypothesis, we analyzed models of cultured adult rat cardiomyocytes as well as investigated myocytes in the failing human myocardium by western blot and confocal microscopy. Fetal remodeling was induced through endothelial morphogens and monitored by the reexpression of Acta2, Actn1, and Actb. Serum-induced hypertrophy was determined by increased surface size and protein content of cardiomyocytes. Serum and morphogens caused reprogramming of Ras/Raf/MEK/ERK. In both models H-Ras, N-Ras, Rap2, B- and C-Raf, MEK1/2 as well as ERK1/2 increased while K-Ras was downregulated. Atrophy, MAPK-dependent ischemic resistance, loss of A-Raf, and reexpression of Rap1 and Erk3 highlighted fetal remodeling, while A-Raf accumulation marked hypertrophy. The knock-down of B-Raf by siRNA reduced MAPK activation and fetal reprogramming. In conclusion, we demonstrate that fetal and hypertrophic remodeling are independent processes and involve reprogramming of the MAPK.
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spelling pubmed-75035712020-09-23 The MEK/ERK Module Is Reprogrammed in Remodeling Adult Cardiomyocytes Thomas, Kubin Ayse, Cetinkaya Natalia, Kubin Peter, Bramlage Bedriye, Sen-Hild Praveen, Gajawada Hakan, Akintürk Markus, Schönburg Wolfgang, Schaper Yeong-Hoon, Choi Miroslav, Barancik Manfred, Richter Int J Mol Sci Article Fetal and hypertrophic remodeling are hallmarks of cardiac restructuring leading chronically to heart failure. Since the Ras/Raf/MEK/ERK cascade (MAPK) is involved in the development of heart failure, we hypothesized, first, that fetal remodeling is different from hypertrophy and, second, that remodeling of the MAPK occurs. To test our hypothesis, we analyzed models of cultured adult rat cardiomyocytes as well as investigated myocytes in the failing human myocardium by western blot and confocal microscopy. Fetal remodeling was induced through endothelial morphogens and monitored by the reexpression of Acta2, Actn1, and Actb. Serum-induced hypertrophy was determined by increased surface size and protein content of cardiomyocytes. Serum and morphogens caused reprogramming of Ras/Raf/MEK/ERK. In both models H-Ras, N-Ras, Rap2, B- and C-Raf, MEK1/2 as well as ERK1/2 increased while K-Ras was downregulated. Atrophy, MAPK-dependent ischemic resistance, loss of A-Raf, and reexpression of Rap1 and Erk3 highlighted fetal remodeling, while A-Raf accumulation marked hypertrophy. The knock-down of B-Raf by siRNA reduced MAPK activation and fetal reprogramming. In conclusion, we demonstrate that fetal and hypertrophic remodeling are independent processes and involve reprogramming of the MAPK. MDPI 2020-09-01 /pmc/articles/PMC7503571/ /pubmed/32882982 http://dx.doi.org/10.3390/ijms21176348 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Thomas, Kubin
Ayse, Cetinkaya
Natalia, Kubin
Peter, Bramlage
Bedriye, Sen-Hild
Praveen, Gajawada
Hakan, Akintürk
Markus, Schönburg
Wolfgang, Schaper
Yeong-Hoon, Choi
Miroslav, Barancik
Manfred, Richter
The MEK/ERK Module Is Reprogrammed in Remodeling Adult Cardiomyocytes
title The MEK/ERK Module Is Reprogrammed in Remodeling Adult Cardiomyocytes
title_full The MEK/ERK Module Is Reprogrammed in Remodeling Adult Cardiomyocytes
title_fullStr The MEK/ERK Module Is Reprogrammed in Remodeling Adult Cardiomyocytes
title_full_unstemmed The MEK/ERK Module Is Reprogrammed in Remodeling Adult Cardiomyocytes
title_short The MEK/ERK Module Is Reprogrammed in Remodeling Adult Cardiomyocytes
title_sort mek/erk module is reprogrammed in remodeling adult cardiomyocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503571/
https://www.ncbi.nlm.nih.gov/pubmed/32882982
http://dx.doi.org/10.3390/ijms21176348
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