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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

Co-induction of cell death and survival pathways by phosphoinositide 3-kinase

Seung Bum Lee1, Sung Hee Hong, Hoguen Kim

  • 1Laboratory of Radiation Tumor Physiology, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul 139-706, Korea.

Life Sciences
|September 13, 2005
PubMed

Insights

Reactive oxygen species (ROS) trigger both cell death and survival pathways. Phosphoinositide 3-kinase (PI3K) amplifies these signals during serum withdrawal, favoring cell death.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • A single stimulus can activate both cell death and survival pathways, indicating shared upstream signaling.
  • Serum withdrawal (SW) in U937 cells induces apoptosis via SAPK/JNK and involves reactive oxygen species (ROS) and phosphoinositide 3-kinase (PI3K).

Purpose of the Study:

  • To define common upstream signaling components regulating cell death and survival pathways.
  • To investigate the role of the ROS/PI3K interaction in activating both apoptotic and survival pathways.

Main Methods:

  • Human U937 cells were exposed to serum-free media to induce apoptosis.
  • Analyzed the activation of SAPK/JNK and NF-kappaB pathways in response to serum withdrawal and exogenous H(2)O(2).
  • Investigated the involvement of PI3K and Akt in these signaling pathways.

Main Results:

  • Serum withdrawal induced apoptosis mediated by SAPK/JNK.
  • The ROS/PI3K interaction was found to activate both SAPK/JNK-dependent apoptosis and NF-kappaB-dependent survival.
  • Akt was not involved in SAPK/JNK or NF-kappaB activation.
  • SAPK activation required higher H(2)O(2) concentrations than NF-kappaB activation.
  • High H(2)O(2) concentrations activated NF-kappaB and SAPK independently of PI3K.

Conclusions:

  • ROS induce both SAPK-dependent apoptotic and NF-kappaB-mediated survival pathways.
  • PI3K amplifies these ROS-induced signals in the serum withdrawal pathway, favoring cell death.
  • Distinct concentrations of ROS differentially regulate apoptotic and survival pathways.

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