skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: The transcription factor MEF2C mediates cardiomyocyte hypertrophy induced by IGF-1 signaling

Abstract

Myocyte enhancer factor 2C (MEF2C) plays an important role in cardiovascular development and is a key transcription factor for cardiac hypertrophy. Here, we describe MEF2C regulation by insulin-like growth factor-1 (IGF-1) and its role in IGF-1-induced cardiac hypertrophy. We found that IGF-1 addition to cultured rat cardiomyocytes activated MEF2C, as evidenced by its increased nuclear localization and DNA binding activity. IGF-1 stimulated MEF2 dependent-gene transcription in a time-dependent manner, as indicated by increased MEF2 promoter-driven reporter gene activity; IGF-1 also induced p38-MAPK phosphorylation, while an inhibitor of p38-MAPK decreased both effects. Additionally, inhibitors of phosphatidylinositol 3-kinase and calcineurin prevented IGF-1-induced MEF2 transcriptional activity. Via MEF2C-dependent signaling, IGF-1 also stimulated transcription of atrial natriuretic factor and skeletal {alpha}-actin but not of fos-lux reporter genes. These novel data suggest that MEF2C activation by IGF-1 mediates the pro-hypertrophic effects of IGF-1 on cardiac gene expression.

Authors:
; ; ; ; ; ; ; ; ;  [1];  [2];  [1];  [2];  [1];  [2];  [2]
  1. Centro FONDAP Estudios Moleculares de la Celula, Facultad de Medicina, Universidad de Chile, Santiago 8380492 (Chile)
  2. (Chile)
Publication Date:
OSTI Identifier:
22199832
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 388; Journal Issue: 1; Other Information: Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACTIN; DNA; GENE REGULATION; GENES; GROWTH FACTORS; HEART; HYPERTROPHY; INSULIN; PHOSPHORYLATION; PROMOTERS; RATS; TIME DEPENDENCE; TRANSCRIPTION; TRANSCRIPTION FACTORS

Citation Formats

Munoz, Juan Pablo, Collao, Andres, Chiong, Mario, Maldonado, Carola, Adasme, Tatiana, Carrasco, Loreto, Ocaranza, Paula, Bravo, Roberto, Gonzalez, Leticia, Diaz-Araya, Guillermo, Facultad de Ciencias Quimicas y Farmaceuticas, Facultad de Medicina, Universidad de Chile, Santiago 8380492, Hidalgo, Cecilia, Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago 8380492, Lavandero, Sergio, E-mail: slavander@uchile.cl, Facultad de Ciencias Quimicas y Farmaceuticas, Facultad de Medicina, Universidad de Chile, Santiago 8380492, and Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago 8380492. The transcription factor MEF2C mediates cardiomyocyte hypertrophy induced by IGF-1 signaling. United States: N. p., 2009. Web. doi:10.1016/J.BBRC.2009.07.147.
Munoz, Juan Pablo, Collao, Andres, Chiong, Mario, Maldonado, Carola, Adasme, Tatiana, Carrasco, Loreto, Ocaranza, Paula, Bravo, Roberto, Gonzalez, Leticia, Diaz-Araya, Guillermo, Facultad de Ciencias Quimicas y Farmaceuticas, Facultad de Medicina, Universidad de Chile, Santiago 8380492, Hidalgo, Cecilia, Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago 8380492, Lavandero, Sergio, E-mail: slavander@uchile.cl, Facultad de Ciencias Quimicas y Farmaceuticas, Facultad de Medicina, Universidad de Chile, Santiago 8380492, & Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago 8380492. The transcription factor MEF2C mediates cardiomyocyte hypertrophy induced by IGF-1 signaling. United States. doi:10.1016/J.BBRC.2009.07.147.
Munoz, Juan Pablo, Collao, Andres, Chiong, Mario, Maldonado, Carola, Adasme, Tatiana, Carrasco, Loreto, Ocaranza, Paula, Bravo, Roberto, Gonzalez, Leticia, Diaz-Araya, Guillermo, Facultad de Ciencias Quimicas y Farmaceuticas, Facultad de Medicina, Universidad de Chile, Santiago 8380492, Hidalgo, Cecilia, Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago 8380492, Lavandero, Sergio, E-mail: slavander@uchile.cl, Facultad de Ciencias Quimicas y Farmaceuticas, Facultad de Medicina, Universidad de Chile, Santiago 8380492, and Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago 8380492. Fri . "The transcription factor MEF2C mediates cardiomyocyte hypertrophy induced by IGF-1 signaling". United States. doi:10.1016/J.BBRC.2009.07.147.
@article{osti_22199832,
title = {The transcription factor MEF2C mediates cardiomyocyte hypertrophy induced by IGF-1 signaling},
author = {Munoz, Juan Pablo and Collao, Andres and Chiong, Mario and Maldonado, Carola and Adasme, Tatiana and Carrasco, Loreto and Ocaranza, Paula and Bravo, Roberto and Gonzalez, Leticia and Diaz-Araya, Guillermo and Facultad de Ciencias Quimicas y Farmaceuticas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 and Hidalgo, Cecilia and Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 and Lavandero, Sergio, E-mail: slavander@uchile.cl and Facultad de Ciencias Quimicas y Farmaceuticas, Facultad de Medicina, Universidad de Chile, Santiago 8380492 and Instituto de Ciencias Biomedicas, Facultad de Medicina, Universidad de Chile, Santiago 8380492},
abstractNote = {Myocyte enhancer factor 2C (MEF2C) plays an important role in cardiovascular development and is a key transcription factor for cardiac hypertrophy. Here, we describe MEF2C regulation by insulin-like growth factor-1 (IGF-1) and its role in IGF-1-induced cardiac hypertrophy. We found that IGF-1 addition to cultured rat cardiomyocytes activated MEF2C, as evidenced by its increased nuclear localization and DNA binding activity. IGF-1 stimulated MEF2 dependent-gene transcription in a time-dependent manner, as indicated by increased MEF2 promoter-driven reporter gene activity; IGF-1 also induced p38-MAPK phosphorylation, while an inhibitor of p38-MAPK decreased both effects. Additionally, inhibitors of phosphatidylinositol 3-kinase and calcineurin prevented IGF-1-induced MEF2 transcriptional activity. Via MEF2C-dependent signaling, IGF-1 also stimulated transcription of atrial natriuretic factor and skeletal {alpha}-actin but not of fos-lux reporter genes. These novel data suggest that MEF2C activation by IGF-1 mediates the pro-hypertrophic effects of IGF-1 on cardiac gene expression.},
doi = {10.1016/J.BBRC.2009.07.147},
journal = {Biochemical and Biophysical Research Communications},
number = 1,
volume = 388,
place = {United States},
year = {Fri Oct 09 00:00:00 EDT 2009},
month = {Fri Oct 09 00:00:00 EDT 2009}
}