| Literature DB >> 19654000 |
Juan Pablo Muñoz1, Andres Collao, Mario Chiong, Carola Maldonado, Tatiana Adasme, Loreto Carrasco, Paula Ocaranza, Roberto Bravo, Leticia Gonzalez, Guillermo Díaz-Araya, Cecilia Hidalgo, Sergio Lavandero.
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.Entities:
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Year: 2009 PMID： 19654000 DOI： 10.1016/j.bbrc.2009.07.147
Source DB: PubMed Journal: Biochem Biophys Res Commun ISSN： 0006-291X Impact factor: 3.575