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

• Published in: American journal of physiology. Lung cellular and molecular physiology 2002-04, Vol.282 (4), p.727-L734
• Main Authors: Santore, Matthew T, McClintock, David S, Lee, Vivian Y, Budinger, G. R. Scott, Chandel, Navdeep S
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Apoptosis - physiology; bcl-X Protein; Caspase 9; Caspases - metabolism; Cytochrome c Group - metabolism; DNA-Binding Proteins - metabolism; Electron Transport - physiology; Epithelial Cells - cytology; Epithelial Cells - metabolism; Humans; Hypoxia - metabolism; Hypoxia - pathology; Hypoxia-Inducible Factor 1; Hypoxia-Inducible Factor 1, alpha Subunit; Lung Neoplasms; Mitochondria - enzymology; NF-kappa B - metabolism; Nuclear Proteins - metabolism; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Respiratory Mucosa - cytology; Respiratory Mucosa - metabolism; Transcription Factors; Transfection; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.00281.2001

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60601 The intracellular signaling pathways that control O 2 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-X L prevented the anoxia-induced cell death by inhibiting the release of cytochrome c and caspase-9 activation. A549 cells devoid of mitochondrial DNA ( °-cells) and lacking a functional electron transport chain were resistant to anoxia-induced apoptosis. A549 cells preconditioned with either hypoxia (1.5% O 2 ) or tumor necrosis factor- , which activated the transcription factors hypoxia-inducible factor-1 or nuclear factor- B, 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. Bcl-X L ; hypoxia; hypoxia inducible factor-1; tumor necrosis factor- ; nuclear factor- B