Induction of Egr-1 mRNA and protein by endothelin 1, angiotensin II and norepinephrine in neonatal cardiac myocytes

The early growth response gene Egr-1 is a nuclear transcription factor know n to serve as an intermediary in a broad range of signal transduction proce sses. Recent studies have assigned Egr-1 a new role as an amplifier of gene expression. Egr-1 mRNA is expressed in the myocardium and is rapidly induc ed in response to hypertrophic stimuli. However, induction of the Egr-1 pro tein has not yet been demonstrated in the myocardium; on the other hand, in skeletal muscle cells we have shown translational regulation of Egr-1. To further investigate the role of Egr-1 in the regulatory mechanisms of a var iety of signal transduction processes we have therefore asked whether bona fide hypertrophic stimuli induce Egr-1 protein subsequently to its mRNA in neonatal rat cardiomyocytes or whether translational block occurs. In confo cal laser studies the Egr-1 protein was nuclearly localized. Norepinephrine (NE, 2 mu M), angiotensin II (AII, 0.1 mu M), and endothelin 1 (E1, 0.1 mu M) each induced the Egr-1 mRNA 6-8 fold and the Egr-1 protein 3-5 fold (n = 3, p < 0.01). Therefore, in contrast to skeletal muscle cells, these stim uli increased Egr-1 mRNA and protein levels. These results point further to the role of Egr-1 as a possible amplifier of signal transduction in the my ocardium.