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This Article Full Text Full Text (PDF) All Versions of this Article: 286/6/H2369    most recent 00741.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (15) Citing Articles via Google Scholar Google Scholar Articles by Taimor, G. Articles by Piper, H. M. Search for Related Content PubMed PubMed Citation Articles by Taimor, G. Articles by Piper, H. M.

Transcription activator protein 1 mediates - but not -adrenergic hypertrophic growth responses in adult cardiomyocytes

Physiologisches Institut, Justus-Liebig-Universität, 35392 Giessen, Germany

Submitted 4 August 2003 ; accepted in final form 30 January 2004

In some models of cardiac hypertrophy, activation of activator protein 1 (AP-1) correlates with growth. However, AP-1 is also activated by stimuli not involved in cardiac growth. This raises the following questions: does AP-1 plays a causal role for cardiomyocyte growth, and is this role model or stimulus dependent? We used a single model to address these questions, i.e., ventricular cardiomyocytes of adult rats, and two growth stimuli, i.e., - and -adrenoceptor agonists [10 µM phenylephrine (PE) and 1 µM isoprenaline (Iso), respectively]. After 1 h of stimulation with PE, mRNA expression of c-Fos and c-Jun was upregulated to 185 ± 32 and 132 ± 13% of control. Fos and Jun proteins formed the AP-1 complex. PE stimulated DNA binding activity of AP-1 to 165 ± 22% of control within 2 h and increased protein synthesis to 161 ± 27% of control and cross-sectional area to 126 ± 4% of control. Inhibition of AP-1 binding activity by cAMP response element (CRE) decoy oligonucleotides abolished both of these growth responses. Iso stimulated AP-1 binding activity to 203 ± 19% of control within 2 h and stimulated protein synthesis to 145 ± 17% of control. However, the growth effect of Iso was not abolished by CRE decoys: Iso increased protein synthesis to 158 ± 17% of control in the presence of CRE. In conclusion, AP-1 is a causal mediator of the -adrenergic, but not the -adrenergic, growth response of cardiomyocytes.

hypertrophy; adrenoceptors; immediate early genes; transcription factors