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Keywords :
Animals; Cells, Cultured; DNA-Binding Proteins/genetics; Early Growth Response Protein 1; Endothelins/antagonists & inhibitors/pharmacology; Genes/drug effects; Heart/drug effects/physiology; Immediate-Early Proteins; Kinetics; Myocardium/metabolism; Oligonucleotides, Antisense/pharmacology; Phenylalanine/metabolism; Protein Biosynthesis; RNA, Messenger/genetics; Rats; Rats, Inbred WKY; Transcription Factors/genetics; Zinc Fingers/genetics
Abstract :
[en] 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.
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