Effect of inhibitors of signal transduction on IGF-1-induced protein synthesis associated with hypertrophy in cultured neonatal rat ventricular myocytes.
IGF-1 increased 2-fold protein synthesis in cardiac myocytes. Genistein, whether added during preincubation or with IGF-1 at the start of incubation, significantly inhibited the IGF-1-induced stimulation of protein synthesis, autophosphorylation of the beta-subunit of IGF-1 receptor and inhibition of ERK. When added 1 or 6 h after IGF-1, however, genistein was without effect. IGF-1-stimulated protein synthesis was also significantly inhibited by PD-098059, staurosporine, and rapamycin, but not by wortmannin, in cardiac myocytes. Some inhibitors produced a reduction in cell size. Activation of the ERK cascade by IGF-1 may be responsible for some of the features associated with cardiac myocyte hypertrophy.
Lavandero
S
S
Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago. slavande@ll.ciq.uchile.cl
Foncea
R
R
Pérez
V
V
Sapag-Hagar
M
M
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006332:Cardiomegaly; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation; D011090:Polyenes / Q000494:pharmacology; D014176:Protein Biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D020123:Sirolimus; D019311:Staurosporine / Q000494:pharmacology; D000077191:Wortmannin
D000730:Androstadienes; D004791:Enzyme Inhibitors; D005419:Flavonoids; D011090:Polyenes; D007334:Insulin-Like Growth Factor I; D019833:Genistein; D017526:Receptor, IGF Type 1; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019311:Staurosporine; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D020123:Sirolimus; D000077191:Wortmannin