6533b86ffe1ef96bd12cdeb3

RESEARCH PRODUCT

Hypertrophic agonists induce the binding of c-Fos to an AP-1 site in cardiac myocytes: implications for the expression of GLUT1

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Objectives: Serum is among the agents known to induce hypertrophy of cardiac myocytes, which occurs concomitant with an increase in AP-1-mediated transcription. We have examined if this effect correlates with changes in the relative abundance of particular AP-1 heterodimers, as their exact composition under these conditions is unknown. Furthermore, we obtained insight on the specific role of c-Fos from studying the induction of the glucose transporter GLUT1 by serum in fibroblasts. Methods: We characterised the AP-1 heterodimers expressed in neonatal cardiac myocytes by supershift electrophoretic mobility shift assay (EMSA) analysis. Quantitative changes in transcription were measured using a luciferase reporter vector, and we examined the expression of the glucose transporter GLUT1 in cardiac myocytes and a c-Fos knockout-derived fibroblast cell line by western blotting. Results: Transcriptionally active AP-1 in combinations of c-Jun, JunD and JunB with Fra1, Fra2 and possibly FosB, are expressed in cardiac myocytes. Hypertrophic stimuli transiently induced AP-1 dimers containing c-Fos, and this was dependent on the ERK mitogen-activated protein kinase pathway and coincided with the activation of AP-1-mediated transcription and the induction of GLUT1 in cardiac myocytes. In fibroblasts, the induction of GLUT1 by serum required the specific expression of c-Fos. Conclusion: Our data suggest that induction of c-Fos containing AP-1 heterodimers may partly activate AP-1-mediated transcription in cardiac myocytes treated with hypertrophic agonists under conditions known to induce GLUT1. Data obtained in fibroblasts treated with serum lead us to hypothesise that c-Fos might play a major role in the regulation of GLUT1 expression.