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

Yoon Jin Lee, Hae Nyun Cho, Jae Won Soh, Gil Ja Jhon, Chul Koo Cho, Hee Yong Chung, Sangwoo Bae, Su Jae Lee, Yun Sil Lee

Research output: Contribution to journalArticlepeer-review

108 Scopus citations

Abstract

Oxidative stress is known to induce apoptosis in a wide variety of cell types, apparently by modulating intracellular signaling pathways. High concentrations of H2O2 have been found to induce apoptosis in L929 mouse fibroblast cells. To elucidate the mechanisms of H 2O2-mediated apoptosis, ERK1/2, p38-MAPK, and JNK1/2 phosphorylation was examined, and ERK1/2 and JNK1/2 were found to be activated by H2O2. Inhibition of ERK1/2 activation by treatment of L929 cells with PD98059 or dominant-negative ERK2 transfection blocked H 2O2-induced apoptosis, while inhibition of JNK1/2 by dominant-negative JNK1 or JNK2 or MKK4 or MKK7 transfection did not affect H2O2-mediated apoptosis. H2O 2-mediated ERK1/2 activation was not only Ras-Raf dependent, but also both tyrosine kinase (PDGFβ receptor and Src) and PKCδ dependent. H2O2-mediated PKCδ-dependent and tyrosine kinase-dependent ERK1/2 activations were independent from each other. Based on the above results, we suggest for the first time that oxidative damage-induced apoptosis is mediated by ERK1/2 phosphorylation which is not only Ras-Raf dependent, but also both tyrosine kinase and PKCδ dependent.

Original languageEnglish
Pages (from-to)251-266
Number of pages16
JournalExperimental Cell Research
Volume291
Issue number1
DOIs
StatePublished - 15 Nov 2003

Keywords

  • Apoptosis
  • ERK1/2 phosphorylation
  • Oxidative stress
  • PKCδ
  • Tyrosine kinase phosphorylation

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