Reference : Inhibition of endothelin-1 induced myocardial protein synthesis by an antisense oligo...
Scientific journals : Article
Human health sciences : Cardiovascular & respiratory systems
Inhibition of endothelin-1 induced myocardial protein synthesis by an antisense oligonucleotide against the early growth response gene-1.
Neyses, Ludwig mailto [University of Luxembourg > Research Office]
Nouskas, J. [> >]
Vetter, H. [> >]
Biochemical and biophysical research communications
[en] 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
[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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