IGF-1 regulates cardiac fibroblast apoptosis induced by osmotic stress

Biochem Biophys Res Commun. 2000 Jun 24;273(1):322-7. doi: 10.1006/bbrc.2000.2934.

Abstract

In this study we have determined the ability of IGF-1 to protect cardiac fibroblasts against osmotic-induced apoptosis and investigated the potential mechanism(s) underlying this protection. Treatment with IGF-1 (1-100 ng/ml) promoted a dose dependent increase in cell survival against osmotic cell death. Both Akt and ERK1/2 were rapidly phosphorylated by IGF-1 and blocked by wortmannin and PD98059, inhibitors of their upstream activators respectively. However, IGF-1-induced protection was mediated via a wortmannin-dependent but PD98059-independent pathway as determined by cell survival assay suggesting a role of PI3-K/Akt. Furthermore, IGF-1 appeared to reduce the activation of a number of early components in the apoptotic pathway in a wortmannin dependent manner including the osmotic stress-induced perturbation in mitochondrial membrane potential, cleavage and activation of caspase-3 and DNA fragmentation. Thus, the results suggest that IGF-1 regulates osmotic stress-induced apoptosis via the activation of the PI3-K/Akt pathway at a point upstream of the mitochondria and caspase-3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Apoptosis / drug effects*
  • Caspase 3
  • Caspases / metabolism
  • Cell Survival / drug effects
  • Cells, Cultured
  • DNA Fragmentation / drug effects
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Fibroblasts / cytology*
  • Fibroblasts / drug effects*
  • Fibroblasts / enzymology
  • Fibroblasts / metabolism
  • Insulin-Like Growth Factor I / antagonists & inhibitors
  • Insulin-Like Growth Factor I / pharmacology*
  • Isoenzymes / chemistry
  • Isoenzymes / metabolism
  • Membrane Potentials / drug effects
  • Mitochondria / drug effects
  • Mitochondria / physiology
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism
  • Myocardium / cytology*
  • Osmolar Concentration
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphorylation / drug effects
  • Protein Kinase C / chemistry
  • Protein Kinase C / metabolism
  • Protein Kinase C-delta
  • Protein Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • Rats
  • Signal Transduction / drug effects

Substances

  • Isoenzymes
  • Peptide Fragments
  • Phosphoinositide-3 Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Insulin-Like Growth Factor I
  • Prkcd protein, rat
  • Akt1 protein, rat
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Protein Kinase C
  • Protein Kinase C-delta
  • Mitogen-Activated Protein Kinases
  • Casp3 protein, rat
  • Caspase 3
  • Caspases