Anoxia-induced apoptosis occurs through a mitochondria-dependent pathway in lung epithelial cells

Matthew T. Santore, David S. McClintock, Vivian Y. Lee, G. R.Scott Budinger, Navdeep S. Chandel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

The intracellular signaling pathways that control O2 deprivation (anoxia)-induced apoptosis have not been fully defined in lung epithelial cells. We show here that the lung epithelial cell line A549 releases cytochrome c and activates caspase-9 followed by DNA fragmentation and plasma membrane breakage in response to anoxia. The antiapoptotic protein Bcl-XL prevented the anoxia-induced cell death by inhibiting the release of cytochrome c and caspase-9 activation. A549 cells devoid of mitochondrial DNA (ρ°-cells) and lacking a functional electron transport chain were resistant to anoxia-induced apoptosis. A549 cells preconditioned with either hypoxia (1.5% O2) or tumor necrosis factor-α, which activated the transcription factors hypoxia-inducible factor-1 or nuclear factor-κB, respectively, did not provide protection from anoxia-induced cell death. These results indicate that A549 cells require a functional electron transport chain and the release of cytochrome c for anoxia-induced apoptosis.

Original languageEnglish (US)
Pages (from-to)L727-L734
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume282
Issue number4 26-4
DOIs
StatePublished - 2002

Keywords

  • Bcl-X
  • Hypoxia
  • Hypoxia inducible factor-1
  • Nuclear factor-κB
  • Tumor necrosis factor-α

ASJC Scopus subject areas

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

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