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Updated: Oct 19, 2026

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Regulation of vascular smooth muscle cell apoptosis. Modulation of bad by a phosphatidylinositol 3-kinase-dependent

H z Bai1, M J Pollman, Y Inishi

  • 1Molecular Vascular Cell Biology Research Laboratory, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA, USA.

Circulation Research
|August 7, 1999
PubMed

Insights

Insulin-like growth factor-I (IGF-I) prevents vascular smooth muscle cell (VSMC) apoptosis by activating the phosphatidylinositol 3-kinase (PI3K) pathway. This pathway inhibits the pro-apoptotic protein Bad, promoting VSMC survival.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cardiovascular Research

Background:

  • Vascular smooth muscle cell (VSMC) apoptosis contributes to cardiovascular diseases.
  • Mitogens like insulin-like growth factor-I (IGF-I) are known to influence cell survival.
  • The precise signaling pathways mediating IGF-I's effects on VSMC apoptosis are not fully understood.

Purpose of the Study:

  • To elucidate the signaling mechanisms by which IGF-I regulates VSMC apoptosis.
  • To investigate the role of the phosphatidylinositol 3-kinase (PI3K) pathway in VSMC survival.
  • To identify downstream targets of IGF-I signaling involved in preventing apoptosis.

Main Methods:

  • Cultured VSMCs were treated with IGF-I and subjected to serum withdrawal.
  • PI3K activity was measured using biochemical assays.
  • Inhibitors of PI3K (wortmannin, LY294002) and dominant-negative PI3K constructs were used to block pathway activity.
  • Expression and phosphorylation of the pro-apoptotic protein Bad were assessed.

Main Results:

  • IGF-I inhibited serum withdrawal-induced VSMC apoptosis in a dose- and time-dependent manner.
  • PI3K activity was elevated in viable VSMCs and decreased upon serum withdrawal, with IGF-I treatment restoring activity.
  • Inhibition of PI3K abolished IGF-I's protective effect against apoptosis.
  • IGF-I promoted the phosphorylation and inactivation of Bad via a PI3K-dependent pathway.

Conclusions:

  • The PI3K signaling pathway is a critical mediator of IGF-I-induced survival in VSMCs.
  • IGF-I prevents VSMC apoptosis by activating PI3K, which in turn leads to the inactivation of the pro-apoptotic protein Bad.
  • Growth factors utilize PI3K-dependent signaling cascades to regulate apoptotic genes and promote vascular cell survival.

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