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 language | English (US) |
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Pages (from-to) | L727-L734 |
Journal | American Journal of Physiology - Lung Cellular and Molecular Physiology |
Volume | 282 |
Issue number | 4 26-4 |
DOIs | |
State | Published - 2002 |
Keywords
- Bcl-X
- Hypoxia
- Hypoxia inducible factor-1
- Nuclear factor-κB
- Tumor necrosis factor-α
ASJC Scopus subject areas
- Physiology (medical)
- Physiology
- Pulmonary and Respiratory Medicine
- Cell Biology