Mitogen-activated protein kinase pathway mediates hyperoxia-induced apoptosis in cultured macrophage cells

Irina Petrache, Mary E. Choi, Leo E. Otterbein, Beek Yoke Chin, Lin L. Mantell, Stuart Horowitz, Augustine M.K. Choi

Research output: Contribution to journalArticle

112 Scopus citations

Abstract

We have previously demonstrated that the lungs of mice can exhibit increased programmed cell death or apoptosis after hyperoxic exposure in vivo. In this report, we show that hyperoxic exposure in vitro can also induce apoptosis in cultured murine macrophage cells (RAW 264.7) as assessed by DNA-laddering, terminal deoxynucleotidyltransferase dUTP nick end- labeling, and nucleosomal assays. To further delineate the signaling pathway of hyperoxia-induced apoptosis in RAW 264.7 macrophages, we first show that hyperoxia can activate the mitogen-activated protein kinase (MAPK) pathway, the extracellular signal-regulated kinases (ERKs) p42/p44, in a time- dependent manner as assessed by increased phosphorylation of ERK1/ERK2 by Western blot analyses. Neither the c-Jun NH2-terminal kinase/stress- activated protein kinase nor the p38 MAPK was activated by hyperoxia in these cells. Chemical or genetic inhibition of the ERK p42/p44 MAPK pathway by PD- 98059, a selective inhibitor of MAPK kinase, and dominant negative mutants of ERK, respectively, attenuated hyperoxia-induced apoptosis as assessed by DNA laddering and nucleosomal ELISAs. Taken together, our data suggest that hyperoxia can induce apoptosis in cultured murine macrophages and that the MAPK pathway mediates hyperoxia-induced apoptosis.

Original languageEnglish (US)
Pages (from-to)L589-L595
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume277
Issue number3 21-3
DOIs
StatePublished - Sep 1999

Keywords

  • Cell death
  • Extracellular signal- regulated kinase
  • Oxygen
  • Programmed cell death
  • Signal transduction

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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