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The MEK/ERK Module Is Reprogrammed in Remodeling Adult Cardiomyocytes.
Kubin, Thomas; Cetinkaya, Ayse; Kubin, Natalia; Bramlage, Peter; Sen-Hild, Bedriye; Gajawada, Praveen; Akintürk, Hakan; Schönburg, Markus; Schaper, Wolfgang; Choi, Yeong-Hoon; Barancik, Miroslav; Richter, Manfred.
Afiliación
  • Kubin T; Department of Cardiac Surgery, Kerckhoff Heart Center, Benekestrasse 2-8, 61231 Bad Nauheim, Germany.
  • Cetinkaya A; Campus Kerckhoff, Justus-Liebig-University Giessen, 61231 Bad Nauheim, Germany.
  • Kubin N; Department of Cardiac Surgery, Kerckhoff Heart Center, Benekestrasse 2-8, 61231 Bad Nauheim, Germany.
  • Bramlage P; Campus Kerckhoff, Justus-Liebig-University Giessen, 61231 Bad Nauheim, Germany.
  • Sen-Hild B; Department of Cardiac Surgery, Kerckhoff Heart Center, Benekestrasse 2-8, 61231 Bad Nauheim, Germany.
  • Gajawada P; Campus Kerckhoff, Justus-Liebig-University Giessen, 61231 Bad Nauheim, Germany.
  • Akintürk H; Institute for Pharmacology and Preventive Medicine, Bahnhofstraße 20, 49661 Cloppenburg, Germany.
  • Schönburg M; Pediatric Heart Center, Justus Liebig University, Feulgenstrasse 10-12, 35392 Giessen, Germany.
  • Schaper W; Department of Cardiac Surgery, Kerckhoff Heart Center, Benekestrasse 2-8, 61231 Bad Nauheim, Germany.
  • Choi YH; Campus Kerckhoff, Justus-Liebig-University Giessen, 61231 Bad Nauheim, Germany.
  • Barancik M; Pediatric Heart Center, Justus Liebig University, Feulgenstrasse 10-12, 35392 Giessen, Germany.
  • Richter M; Department of Cardiac Surgery, Kerckhoff Heart Center, Benekestrasse 2-8, 61231 Bad Nauheim, Germany.
Int J Mol Sci ; 21(17)2020 09 01.
Article en En | MEDLINE | ID: mdl-32882982
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación de la Expresión Génica / Proteínas Quinasas Activadas por Mitógenos / Miocitos Cardíacos / Quinasas MAP Reguladas por Señal Extracelular / Reprogramación Celular / Remodelación Vascular Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2020 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación de la Expresión Génica / Proteínas Quinasas Activadas por Mitógenos / Miocitos Cardíacos / Quinasas MAP Reguladas por Señal Extracelular / Reprogramación Celular / Remodelación Vascular Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2020 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Suiza