Poly(ADP-ribose)polymerase activation mediates lung epithelial cell death in vitro but is not essential in hyperoxia-induced lung injury

Pagano Aurrand-Lions, Alessandra; Pitteloud, Claire; Reverdin, Coralie; Ruchonnet, Isabelle; Donati, Yves Richard; Barazzone, Constance

doi:10.1165/rcmb.2004-0361OC

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Title		Poly(ADP-ribose)polymerase activation mediates lung epithelial cell death in vitro but is not essential in hyperoxia-induced lung injury
Authors		Pagano Aurrand-Lions, Alessandra Pitteloud, Claire Reverdin, Coralie Ruchonnet, Isabelle Donati, Yves Richard Barazzone, Constance
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		DOI: 10.1165/rcmb.2004-0361OC PMID: 16151053
Full text		Article (Published version) (408 Kb) - Limited access to UNIGE
Structures		Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie Faculté de médecine / Section de médecine clinique / Département de pédiatrie, gynécologie et obstétrique
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