| Poly(ADP-ribose) polymerase inhibition prevents both apoptotic-like delayed neuronal death and necrosis after H(2)O(2) injury. | |
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MedLine Citation:
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PMID: 12091461 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Toxic reactive oxygen species (ROS) such as hydrogen peroxide, nitric oxide, superoxide, and the hydroxyl radical are generated in a variety of neuropathological conditions and cause significant DNA damage. We determined the effects of 3-aminobenzamide (AB), an inhibitor of the DNA repair enzyme poly(ADP-ribose) polymerase (PARP), on cell death in differentiated PC12 cells, a model of sympathetic neurons, after H(2) O(2) injury. Exposure to 0.5 mm H(2) O(2) resulted in a significant decrease in intracellular NAD(H), NADP(H), and ATP levels. This injury resulted in the death of 90% of the cells with significant necrosis early (2 h) after injury and increased apoptosis (12-24 h after injury), as measured by PS exposure and the presence of cytoplasmic oligonucleosomal fragments. Treatment with 2.5 mm AB restored pyridine nucleotide and ATP levels and ameliorated cell death (65% versus 90%) by decreasing the extent of both necrosis and apoptosis. Interestingly, we observed that H(2) O(2) -induced injury caused a delayed cell death exhibiting features of apoptosis but in which caspase-3 like activity was absent. Moreover, pretreatment with AB restored caspase-3-like activity. Our results suggest that apoptosis and necrosis are both triggered by PARP overactivation, and that maintenance of cellular energy levels after injury by inhibiting PARP shifts cell death from necrosis to apoptosis. |
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Authors:
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Kasie K Cole; J Regino Perez-Polo |
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: Journal of neurochemistry Volume: 82 ISSN: 0022-3042 ISO Abbreviation: J. Neurochem. Publication Date: 2002 Jul |
Date Detail:
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Created Date: 2002-07-01 Completed Date: 2002-08-05 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 2985190R Medline TA: J Neurochem Country: England |
Other Details:
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Languages: eng Pagination: 19-29 Citation Subset: IM |
Affiliation:
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Department of Anatomy and Neurosciences, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0652, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphate
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metabolism Animals Apoptosis / drug effects* Benzamides / pharmacology* Caspase 3 Caspases / metabolism Cell Death / drug effects Cell Survival / drug effects DNA Fragmentation / drug effects Dose-Response Relationship, Drug Enzyme Inhibitors / pharmacology Hydrogen Peroxide / toxicity* NAD / metabolism NADP / metabolism Necrosis* Neurons / cytology, drug effects*, enzymology Neuroprotective Agents / pharmacology PC12 Cells Poly Adenosine Diphosphate Ribose / biosynthesis Poly(ADP-ribose) Polymerases / antagonists & inhibitors*, metabolism Rats |
| Grant Support | |
ID/Acronym/Agency:
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P01 NS 39161/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Benzamides; 0/Enzyme Inhibitors; 0/Neuroprotective Agents; 26656-46-2/Poly Adenosine Diphosphate Ribose; 3544-24-9/3-aminobenzamide; 53-59-8/NADP; 53-84-9/NAD; 56-65-5/Adenosine Triphosphate; 7722-84-1/Hydrogen Peroxide; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/Casp3 protein, rat; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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