IGF-1 Regulates Cardiac Fibroblast Apoptosis Induced by Osmotic Stress

IGF-1 Regulates Cardiac Fibroblast Apoptosis Induced by Osmotic Stress 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Biochemical and Biophysical Research Communications Elsevier

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Publisher
Elsevier
Copyright
Copyright © 2000 Academic Press
ISSN
0006-291x
DOI
10.1006/bbrc.2000.2934
pmid
10873605
Publisher site
See Article on Publisher Site

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.

Journal

Biochemical and Biophysical Research CommunicationsElsevier

Published: Jun 24, 2000

References

  • IGF-1 regulates apoptosis of cardiac myocyte induced by osmotic stress
    Morales, M.P.; Galvez, A.; Eltit, J.M.; Ocaranza, P.; Diaz-Araya, G.; Lavandero, S.
  • Cell death: The significance of apoptosis
    Wyllie, A.H.; Kerr, J.F.; Currie, A.R.
  • Mechanisms and functions of cell death
    Ellis, R.E.; Yuan, J.; Horvitz, H.R.
  • Osmotic stress induces both secretion and apoptosis in rat alveolar type II cells
    Edwards, Y.S.; Sutherlands, L.M.; Power, J.H.T.; Nicholas, T.E.; Murray, A.W.
  • Mechanisms and consequences of activation of protein kinase B/Akt
    Downward, J.
  • MAPK activation determines renal epithelial cell survival during oxidative injury
    Di Mari, J.F.; Davis, R.; Safirstein, R.L.

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