Induction of immediate-early genes by angiotensin II and endothelin-1 in adult rat cardiomyocytes.
OBJECTIVE
Few molecular signals for induction of myocardial hypertrophy have been identified. This study was carried out to investigate the action of angiotensin II and endothelin on the growth- and differentiation-related genes Egr-1 (early growth response gene 1) and c-fos in isolated adult rat cardiomyocytes.


METHODS
Cardiac myocytes from male Wistar-Kyoto rats were isolated and incubated with angiotensin II and endothelin-1 in Dulbecco's modified Eagle's medium. RNA was isolated and blotted, and densitometric analysis was performed. All experiments were repeated at least three times.


RESULTS
Endothelin-1 (10(-7) mmol/l) induced a 20-25-fold rise in Egr-1 messenger RNA within 15 min. This effect was dose-dependent. c-fos was induced 10-20-fold within 15 min with similar dose-response characteristics. Angiotensin II also induced Egr-1 and c-fos with kinetics similar to endothelin but a cofactor from fetal calf serum was needed for full c-fos expression. The protein kinase C activator phorbol 12-myristate 13-acetate also induced Egr-1.


CONCLUSIONS
The results identify Egr-1 and c-fos as target genes for the action of endothelin and angiotensin II in the adult myocardium suggesting that induction of the genes may be part of the signal transduction pathway for angiotensin II and endothelin in the myocardium.
Neyses
L
L
Medical Policlinic, University of Bonn, Germany.
Nouskas
J
J
Luyken
J
J
Fronhoffs
S
S
Oberdorf
S
S
Pfeifer
U
U
Williams
R S
RS
Sukhatme
V P
VP
Vetter
H
H
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D006332:Cardiomegaly / Q000209:etiology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics*; D051766:Early Growth Response Protein 1; D016232:Endothelins / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D017781:Genes, Immediate-Early / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects*; D017874:Immediate-Early Proteins; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D012313:RNA / Q000032:analysis; D051381:Rats; D011921:Rats, Inbred WKY; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D016232:Endothelins; D017874:Immediate-Early Proteins; D014157:Transcription Factors; D000804:Angiotensin II; D012313:RNA