

![]() |
Poly(ADP-ribose)polymerase activation mediates lung epithelial cell death in vitro but is not essential in hyperoxia-induced lung injury |
|
Authors | ||
Published in | American journal of respiratory cell and molecular biology. 2005, vol. 33, no. 6, p. 555-64 | |
Abstract | Hyperoxia induces extensive DNA damage and lung cell death by apoptotic and nonapoptotic pathways. We analyzed the regulation of Poly(ADP-ribose)polymerase-1 (PARP-1), a nuclear enzyme activated by DNA damage, and its relation to cell death during hyperoxia in vitro and in vivo. In lung epithelial-derived A549 cells, which are known to die by necrosis when exposed to oxygen, a minimal amount of PARP-1 was cleaved, correlating with the absence of active caspase-3. Conversely, in primary lung fibroblasts, which die mainly by apoptosis, the complete cleavage of PARP-1 was concomitant to the induction of active caspase-3, as assessed by Western blot and caspase activity. Blockade of caspase activity by Z-VAD reduced the amount of cleaved PARP-1 in fibroblasts. Hyperoxia induced PARP activity in both cell types, as revealed by poly-ADP-ribose accumulation. In A549 cells, the final outcome of necrosis was dependent on PARP activity because it was prevented by the PARP inhibitor 3-aminobenzamide. In contrast, apoptosis of lung fibroblasts was not sensitive to 3-aminobenzamide and was not affected by PARP-1 deletion. In vivo, despite evidence of PARP activation in hyperoxia-exposed mouse lungs, absence of PARP-1 did not change the extent of lung damage, arguing for redundant oxidative stress-induced cell death pathways. | |
Keywords | Animals — Apoptosis — Benzamides/pharmacology — Blotting, Western — Caspase 3 — Caspases/metabolism — Cell Line, Tumor — Enzyme Activation — Epithelial Cells/enzymology/pathology — Fibroblasts/enzymology/pathology — Humans — Hyperoxia/enzymology — In Vitro Techniques — L-Lactate Dehydrogenase/metabolism — Lung/enzymology/pathology — Mice — Mice, Inbred C57BL — Mice, Knockout — Poly(ADP-ribose) Polymerases/metabolism — Pulmonary Alveoli/cytology/metabolism | |
Identifiers | PMID: 16151053 | |
Full text | ||
Structures | ||
Research group | Facteurs influençants le développement pulmonaire: étude translationnelle chez l'animal et l'homme (182) | |
Citation (ISO format) | PAGANO AURRAND-LIONS, Alessandra et al. Poly(ADP-ribose)polymerase activation mediates lung epithelial cell death in vitro but is not essential in hyperoxia-induced lung injury. In: American journal of respiratory cell and molecular biology, 2005, vol. 33, n° 6, p. 555-64. doi: 10.1165/rcmb.2004-0361OC https://archive-ouverte.unige.ch/unige:46633 |