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

Article Article scientifique Article Poly(ADP-ribose)polymerase activation mediates lung epithelial cell death in vitro but is not essential in hyperoxia-induced lung injury eng 2005 author Pagano Aurrand-Lions Alessandra 99887 author Pitteloud Claire 524168 author Reverdin Coralie 516327 author Ruchonnet Isabelle 0000-0003-4771-875X 106509 author Donati Yves Richard 24165 author Barazzone Constance 29124 555-564 10.1165/rcmb.2004-0361OC 16151053 1044-1549 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. 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 Dewey 616.07 Dewey 618 137 Département de pathologie et immunologie 21F 58 Département de pédiatrie, gynécologie et obstétrique 223 false 148 Facteurs influençants le développement pulmonaire: étude translationnelle chez l'animal et l'homme 182 American journal of respiratory cell and molecular biology 33 6 c2fe2c48-b27e-4a5a-8c18-4c4d4cb7d266 Article (Published version) Restricted 555-564.pdf 417762 application/pdf restrictedAccess 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

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Poly(ADP-ribose)polymerase activation mediates lung epithelial cell death in vitro but is not essential in hyperoxia-induced lung injury	American journal of respiratory cell and molecular biology			2005	586	0

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Reverdin, Coralie