title: Expression of nuclear proto-oncogenes in isoproterenol-induced cardiac hypertrophy.
abstract: Rat hearts infused with the beta-adrenergic agonist isoproterenol were examined for the expression of several nuclear proto-oncogenes (c-fos, fosB, c-jun, junB, and junD) and the immediate early gene Egr-1. During the first 24 h after the start of infusion, a strong but transient expression of c-fos was observed. Expression of c-jun and junD were not elevated whereas junB was. By using specific antagonists to the alpha- (prazosin) and beta-adrenergic receptor (propranolol), a beta-adrenoceptor-specific blockade of the isoproterenol-mediated nuclear response was demonstrated. In situ hybridization localized c-fos expression to cardiac myocytes. Labelling was distributed focally in the left and right ventricles, and was strong and homogeneous in the atria. In contrast to beta-adrenergic stimulation, alpha-adrenoceptor stimulation with phenylephrine and norepinephrine caused the induction of c-jun and Egr-1 in addition to the proto-oncogenes induced by isoproterenol. Thus distinct programs of early response gene expression were expressed in response to alpha- versus beta-adrenergic stimulation.
authors.affiliation: Max-Planck-Institute, Department of Experimental Cardiology, Bad Nauheim, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Brand
authors.forename: H S
authors.initials: HS
authors.lastname: Sharma
authors.forename: W
authors.initials: W
authors.lastname: Schaper
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D015152:Blotting, Northern; D006332:Cardiomegaly / Q000139:chemically induced / Q000378:metabolism*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D015342:DNA Probes; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects / Q000502:physiology*; D016758:Genes, jun / Q000187:drug effects / Q000502:physiology*; D017403:In Situ Hybridization; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D015342:DNA Probes; D007545:Isoproterenol