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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

Oxidative stress-induced apoptosis is mediated by ERK1/2 phosphorylation

Yoon-Jin Lee1, Hae-Nyun Cho, Jae-Won Soh

  • 1Division of Molecular Life Sciences, Ewha Woman's University, College of Natural Science, Seoul 120-750, Korea.

Experimental Cell Research
|November 5, 2003
PubMed

Insights

Oxidative stress triggers apoptosis via ERK1/2 activation in mouse cells. This process depends on Ras-Raf, tyrosine kinases, and PKCdelta, but not JNK1/2 signaling pathways.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Oxidative stress is a known inducer of apoptosis across various cell types.
  • Hydrogen peroxide (H2O2) at high concentrations induces apoptosis in L929 mouse fibroblast cells.
  • Intracellular signaling pathways are modulated during oxidative stress-induced apoptosis.

Purpose of the Study:

  • To elucidate the specific mechanisms underlying H2O2-mediated apoptosis in L929 cells.
  • To investigate the roles of ERK1/2, p38-MAPK, and JNK1/2 signaling pathways in this process.

Main Methods:

  • Examined phosphorylation of ERK1/2, p38-MAPK, and JNK1/2 in response to H2O2.
  • Utilized PD98059 inhibitor and dominant-negative transfections (ERK2, JNK1, JNK2, MKK4, MKK7) to block specific pathways.
  • Investigated the upstream activators of H2O2-mediated ERK1/2 activation, including Ras-Raf, tyrosine kinases (PDGFbeta receptor, Src), and PKCdelta.

Main Results:

  • H2O2 activated both ERK1/2 and JNK1/2 pathways.
  • Inhibition of ERK1/2 activation blocked H2O2-induced apoptosis.
  • Inhibition of JNK1/2 did not affect H2O2-mediated apoptosis.
  • ERK1/2 activation was dependent on Ras-Raf, tyrosine kinases, and PKCdelta.
  • Tyrosine kinase- and PKCdelta-dependent ERK1/2 activations were independent of each other.

Conclusions:

  • Oxidative damage-induced apoptosis is mediated by ERK1/2 phosphorylation.
  • This ERK1/2 activation is dependent on Ras-Raf, tyrosine kinases, and PKCdelta.
  • JNK1/2 signaling is not involved in H2O2-induced apoptosis in this cellular model.

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