Inhibition of endothelin-1 induced myocardial protein synthesis by an antisense oligonucleotide against the early growth response gene-1.
We explored the role of the recently discovered "early growth response gene-1 (Egr-1)" in the induction of myocardial protein synthesis by endothelin-1. Endothelin-1 stimulated protein synthesis (i.e. 3H-phenylalanine incorporation) in isolated adult rat cardiomyocytes more than 2-fold. Addition of a 15mer Egr-1 antisense oligodeoxyribonucleotide complementary to the first 5 codons of the Egr-1 mRNA completely blocked endothelin-induced protein synthesis. A single base mismatch in the oligonucleotide sequence abolished the inhibitory effect. T3-induced stimulation of protein synthesis was unaffected by the antisense oligonucleotide. These results indicate that the Egr-1 gene product is involved (putatively as a third messenger) in the signal transduction cascade initiated by endothelin-1 which eventually culminates in the induction of cardiac protein synthesis.
Neyses
L
L
Medical Policlinic, University of Bonn, Germany.
Nouskas
J
J
Vetter
H
H
D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics*; D051766:Early Growth Response Protein 1; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005796:Genes / Q000187:drug effects*; D006321:Heart / Q000187:drug effects / Q000502:physiology; D017874:Immediate-Early Proteins; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D010649:Phenylalanine / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011921:Rats, Inbred WKY; D014157:Transcription Factors / Q000235:genetics*; D016335:Zinc Fingers / Q000235:genetics
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D016232:Endothelins; D017874:Immediate-Early Proteins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D014157:Transcription Factors; D010649:Phenylalanine