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

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.