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 known to serve as an intermediary in a broad range of signal transduction processes. 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 induced in response to hypertrophic stimuli. However, induction of the Egr-1 protein 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 variety 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 confocal laser studies the Egr-1 protein was nuclearly localized. Norepinephrine (NE, 2 microM), angiotensin II (AII, 0.1 microM), and endothelin 1 (E1, 0.1 microM) 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 stimuli 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 myocardium.
Shamim
A
A
Department of Medicine, University of Würzburg, Germany.
Pelzer
T
T
Grohé
C
C
Neyses
L
L
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D015152:Blotting, Northern; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D051766:Early Growth Response Protein 1; D019332:Endothelin-1 / Q000502:physiology*; D019085:Fluorescent Antibody Technique, Direct; D005786:Gene Expression Regulation / Q000187:drug effects; D017874:Immediate-Early Proteins / Q000096:biosynthesis; D008856:Microscopy, Fluorescence; D009206:Myocardium / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D009638:Norepinephrine / Q000502:physiology*; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D019332:Endothelin-1; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D000804:Angiotensin II; D009638:Norepinephrine