Document Detail


Role of superoxide in poly(ADP-ribose) polymerase upregulation after transient cerebral ischemia.
MedLine Citation:
PMID:  12750003     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Oxidative stress plays a pivotal role in ischemic-reperfusion cell injury. Oxygen-derived free radicals trigger DNA strand damage, which is responsible for the activation of poly(ADP-ribose) polymerase (PARP). Recent studies have shown that peroxynitrite is the primary mediator of DNA damage and, hence, PARP activation after ischemia. PARP activation depletes NAD and ATP pools, ultimately resulting in necrotic cell death by loss of energy stores. Our study shows that PARP is upregulated as early as 15 min after 1 h of transient focal cerebral ischemia and remains for 8 h. We also examined the role of superoxide in PARP induction using copper/zinc-superoxide dismutase transgenic mice. Immunohistochemical and Western blotting data showed that there was no increased induction in PARP expression in these mice, suggesting that one of the mechanisms by which ischemic injury is attenuated in these mice might be by the inhibition of PARP induction. Furthermore, double staining of ischemic tissue with a PARP antibody and terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling (TUNEL) indicated that most cells that are positive for TUNEL do not stain for the PARP antibody, confirming recent reports that PARP activation is involved in necrotic cell death rather than apoptosis during ischemic-reperfusion injury.
Authors:
Purnima Narasimhan; Miki Fujimura; Nobuo Noshita; Pak H Chan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Brain research. Molecular brain research     Volume:  113     ISSN:  0169-328X     ISO Abbreviation:  Brain Res. Mol. Brain Res.     Publication Date:  2003 May 
Date Detail:
Created Date:  2003-05-16     Completed Date:  2003-08-18     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8908640     Medline TA:  Brain Res Mol Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  28-36     Citation Subset:  IM    
Affiliation:
Department of Neurosurgery, Stanford University School of Medicine, CA 94305, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Death / genetics*
Cerebral Cortex / enzymology,  pathology,  physiopathology
Cytochrome c Group / metabolism
Immunohistochemistry
Ischemic Attack, Transient / enzymology*,  genetics
Male
Mice
Mice, Transgenic
Nerve Degeneration / enzymology*,  genetics
Oxidative Stress / genetics*
Poly(ADP-ribose) Polymerases
Proteins / metabolism*
Superoxide Dismutase / genetics,  metabolism
Superoxides / metabolism*
Up-Regulation / genetics*
Grant Support
ID/Acronym/Agency:
NS 25372/NS/NINDS NIH HHS; NS 36147/NS/NINDS NIH HHS; NS 38653/NS/NINDS NIH HHS; P50 NS 14534/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Cytochrome c Group; 0/Proteins; 11062-77-4/Superoxides; EC 1.15.1.-/superoxide dismutase 1; EC 1.15.1.1/Superoxide Dismutase; EC 2.4.2.30/Parp1 protein, mouse; EC 2.4.2.30/Poly(ADP-ribose) Polymerases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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