Effect of inhibitors of signal transduction on IGF-1-induced protein synthesis associated with hypertrophy in cultured neonatal rat ventricular myocytes

FEBS Lett. 1998 Jan 30;422(2):193-6. doi: 10.1016/s0014-5793(98)00008-8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androstadienes / pharmacology
  • Animals
  • Animals, Newborn
  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cardiomegaly
  • Cells, Cultured
  • Enzyme Inhibitors / pharmacology*
  • Flavonoids / pharmacology
  • Genistein / pharmacology
  • Heart / drug effects*
  • Heart Ventricles
  • Insulin-Like Growth Factor I / pharmacology*
  • Myocardium / cytology
  • Myocardium / metabolism*
  • Phosphorylation
  • Polyenes / pharmacology
  • Protein Biosynthesis*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, IGF Type 1 / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Sirolimus
  • Staurosporine / pharmacology
  • Wortmannin

Substances

  • Androstadienes
  • Enzyme Inhibitors
  • Flavonoids
  • Polyenes
  • Insulin-Like Growth Factor I
  • Genistein
  • Receptor, IGF Type 1
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Staurosporine
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
  • Sirolimus
  • Wortmannin