| Mediation of poly(ADP-ribose) polymerase-1-dependent cell death by apoptosis-inducing factor. | |
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MedLine Citation:
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PMID: 12114629 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Poly(ADP-ribose) polymerase-1 (PARP-1) protects the genome by functioning in the DNA damage surveillance network. PARP-1 is also a mediator of cell death after ischemia-reperfusion injury, glutamate excitotoxicity, and various inflammatory processes. We show that PARP-1 activation is required for translocation of apoptosis-inducing factor (AIF) from the mitochondria to the nucleus and that AIF is necessary for PARP-1-dependent cell death. N-methyl-N'-nitro-N-nitrosoguanidine, H2O2, and N-methyl-d-aspartate induce AIF translocation and cell death, which is prevented by PARP inhibitors or genetic knockout of PARP-1, but is caspase independent. Microinjection of an antibody to AIF protects against PARP-1-dependent cytotoxicity. These data support a model in which PARP-1 activation signals AIF release from mitochondria, resulting in a caspase-independent pathway of programmed cell death. |
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Authors:
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Seong-Woon Yu; Hongmin Wang; Marc F Poitras; Carmen Coombs; William J Bowers; Howard J Federoff; Guy G Poirier; Ted M Dawson; Valina L Dawson |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Science (New York, N.Y.) Volume: 297 ISSN: 1095-9203 ISO Abbreviation: Science Publication Date: 2002 Jul |
Date Detail:
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Created Date: 2002-07-12 Completed Date: 2002-08-02 Revised Date: 2007-03-19 |
Medline Journal Info:
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Nlm Unique ID: 0404511 Medline TA: Science Country: United States |
Other Details:
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Languages: eng Pagination: 259-63 Citation Subset: IM |
Affiliation:
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Department of Neurology and Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Active Transport, Cell Nucleus Animals Antibodies / immunology Apoptosis* Apoptosis Inducing Factor Caspases / antagonists & inhibitors, metabolism Cell Nucleus / metabolism Cells, Cultured Cytochrome c Group / metabolism Enzyme Activation Enzyme Inhibitors / pharmacology Flavoproteins / immunology, metabolism* Hydrogen Peroxide / pharmacology Membrane Potentials Membrane Proteins / immunology, metabolism* Methylnitronitrosoguanidine / pharmacology Mice Mice, Knockout Mitochondria / metabolism, physiology N-Methylaspartate / metabolism, pharmacology NAD / metabolism Neurons / cytology, physiology Oxidative Stress Poly(ADP-ribose) Polymerases / antagonists & inhibitors, genetics, metabolism* Proto-Oncogene Proteins c-bcl-2 / metabolism Receptors, N-Methyl-D-Aspartate / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Antibodies; 0/Apoptosis Inducing Factor; 0/Cytochrome c Group; 0/Enzyme Inhibitors; 0/Flavoproteins; 0/Membrane Proteins; 0/Pdcd8 protein, mouse; 0/Proto-Oncogene Proteins c-bcl-2; 0/Receptors, N-Methyl-D-Aspartate; 53-84-9/NAD; 6384-92-5/N-Methylaspartate; 70-25-7/Methylnitronitrosoguanidine; 7722-84-1/Hydrogen Peroxide; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/Caspases |
| Comments/Corrections | |
Comment In:
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Science. 2002 Jul 12;297(5579):200-1
[PMID:
12114611
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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