| Poly(ADP-ribose)polymerase activation mediates lung epithelial cell death in vitro but is not essential in hyperoxia-induced lung injury. | |
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MedLine Citation:
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PMID: 16151053 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Alessandra Pagano; Claire Pitteloud; Coralie Reverdin; Isabelle Métrailler-Ruchonnet; Yves Donati; Constance Barazzone Argiroffo |
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Publication Detail:
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Type: Comparative Study; In Vitro; Journal Article; Research Support, Non-U.S. Gov't Date: 2005-09-08 |
Journal Detail:
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Title: American journal of respiratory cell and molecular biology Volume: 33 ISSN: 1044-1549 ISO Abbreviation: Am. J. Respir. Cell Mol. Biol. Publication Date: 2005 Dec |
Date Detail:
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Created Date: 2005-11-18 Completed Date: 2006-01-10 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8917225 Medline TA: Am J Respir Cell Mol Biol Country: United States |
Other Details:
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Languages: eng Pagination: 555-64 Citation Subset: IM |
Affiliation:
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Departments of Pediatrics and Pathology, Centre Médical Universitaire, 1 rue Michel Servet, 1211 Geneva 4, Switzerland. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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* L-Lactate Dehydrogenase / metabolism Lung / enzymology, pathology* Mice Mice, Inbred C57BL Mice, Knockout Poly(ADP-ribose) Polymerases / metabolism* Pulmonary Alveoli / cytology, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Benzamides; 3544-24-9/3-aminobenzamide; EC 1.1.1.27/L-Lactate Dehydrogenase; EC 2.4.2.30/PARP1 protein, human; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 2.4.2.30/poly(ADP-ribose)polymerase-1, mouse; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Casp3 protein, mouse; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases |
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