Adenovirus infection of myocardial cells induces an enhanced sensitivity to beta-adrenergic agonists by increasing the concentration of the stimulatory G-protein.
Neonatal rat cardiocytes were infected with a recombinant adenovirus type 5 containing the SV40 early promoter-Gsa fusion gene in order to evaluate the presumed role of the stimulatory G-protein (Gs) in hypertrophy of myocardial cells. In vitro infection of myocardial cells with the recombinant adenovirus induced a 79-fold increase in Gs alpha mRNA and a 5-fold increase in Gs alpha protein, which was accompanied by a pronounced cell hypertrophy but not cell proliferation. Interestingly, adenovirus-infected cells displayed features of cell hypertrophy, an increase in sodium fluoride-stimulatible membrane-bound activity of adenylyl cyclase, and an enhanced beta-adrenergic sensitivity irrespective of the presence or absence of the SV40 early promoter-Gs alpha fusion gene in the virus. While the recombinant adenovirus induced a 5-fold versus 3-fold increase for plain adenovirus in cellular Gs alpha, membrane-bound Gs alpha was increased about 2-fold in both instances, which can explain similar increase in the G-protein-modulated adenylyl cyclase activity determined in membranes derived from myocardial cells infected with both types of the virus. It is concluded that adenovirus infection per se can lead to overexpression of Gs alpha and myocardial hypertrophy and thus may be of importance in the pathogenesis of virus-induced cardiomyopathy.
Novotny
J
J
Wallenberg Laboratory for Cardiovascular Research, Gothenburg University, Sweden.
Gustafson
B
B
Kvapil
P
P
Ransnäs
L A
LA
D000260:Adenoviruses, Human / Q000235:genetics* / Q000502:physiology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D006332:Cardiomegaly / Q000209:etiology*; D002478:Cells, Cultured; D019204:GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005822:Genetic Vectors; D006321:Heart / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology; D015879:Myosin Subfragments / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013539:Simian virus 40 / Q000235:genetics
D000318:Adrenergic beta-Agonists; D015879:Myosin Subfragments; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases