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. Genistei n, whether added during preincubation or with IGF-I at the start of in cubation, significantly inhibited the IGF-1-induced stimulation of pro tein synthesis, autophosphorylation of the beta-subunit of IGF-1 recep tor and inhibition of ERK. When added 1 or 6 h after IGF-I, however, g enistein was without effect. IGF-l-stimulated protein synthesis was al so 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 mag b e responsible for some of the features associated with cardiac myocyte hypertrophy. (C) 1998 Federation of European Biochemical Societies.