Load-induced transcriptional activation of c-jun in XXXX myocardium: regulation by myocyte enhancer factor 2.

@entity1184 @entity2647 @entity28141 @entity35
The increased expression of immediate-early genes is a key feature of the myocardial response to @entity1184 stimuli. In this study, we investigated whether pressure overload or @entity2647 treatment stimulated myocyte enhancer factor 2 (MEF2)-dependent transcriptional activation of c-jun in cardiac myocytes. Western blotting and immunohistochemical analysis of @entity35 myocardium demonstrated that p70(MEF2) is highly expressed in the @entity35 heart and is predominantly located at the nuclei of cardiac myocytes. Electrophoretic mobility shift assays of myocardial nuclear extracts revealed a consistent DNA binding activation of MEF2 after 1 and 2 hours of pressure overload. We further showed that pressure overload induced a progressive nuclear translocation and activation of @entity28141 ( @entity28141 ). Coimmunoprecipitation and in vitro kinase assays indicated that the activation of @entity28141 was paralleled by increased association of @entity28141 /p70(MEF2) and by enhanced ability of @entity28141 to phosphorylate p70(MEF2). Experiments with in vivo transfection of the left ventricle with the c-jun promoter reporter gene showed that pressure overload induced a consistent increase of c-jun transcriptional activity in the @entity35 myocardium. Rendering the MEF2 site of the c-jun plasmid inactive by mutation abolished the load-induced activation of the c-jun promoter reporter gene. Mutation of the MEF2 site also abolished the @entity2647 -induced c-jun promoter activation in neonatal @entity35 ventricular myocytes. In addition, we demonstrated that neonatal @entity35 ventricular myocyte transfection with @entity28141 -antisense oligodeoxynucleotide inhibited the @entity2647 -induced c-jun promoter activation. These findings identify MEF2 as a potential regulator of c-jun transactivation and suggest that @entity28141 might be an important mediator of MEF2 and c-jun promoter activation in response to @entity1184 stimuli in cardiac myocytes.
