| Activation of poly(ADP-ribose) polymerase in circulating leukocytes during myocardial infarction. | |
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MedLine Citation:
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PMID: 14770035 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Myocardial ischemia-reperfusion can lead to increased oxidative stress both locally and in circulating leukocytes. Oxidant-mediated DNA single strand breaks are known to activate the nuclear enzyme poly(ADP-ribose) polymerase (PARP) in various forms of shock, inflammation, and ischemia-reperfusion injury. The aim of the current study was to investigate whether a local insult such as myocardial ischemia-reperfusion is sufficient to lead to activation of PARP in circulating leukocytes. In anesthetized rats myocardial ischemia-reperfusion was induced by transient ligation of the left anterior descending coronary artery. There was a marked increase in poly(ADP-ribosyl)ation of proteins in homogenates of leukocytes isolated from rats at the end of the reperfusion period. Poly(ADP-ribosyl)ation was inhibited by administration of the pharmacologic PARP inhibitor INO-1001 (30 mg/kg) to the rats. We conclude that local insults, such as myocardial reperfusion injury, are sufficient to activate PARP in circulating leukocytes. PARP activation in circulating cells may mediate certain systemic effects of local ischemia-reperfusion injury such as inflammatory mediator production and remote organ injury. |
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Authors:
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Kanneganti G K Murthy; Chun-Yang Xiao; Jon G Mabley; Min Chen; Csaba Szabó |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Shock (Augusta, Ga.) Volume: 21 ISSN: 1073-2322 ISO Abbreviation: Shock Publication Date: 2004 Mar |
Date Detail:
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Created Date: 2004-02-10 Completed Date: 2004-10-19 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 9421564 Medline TA: Shock Country: United States |
Other Details:
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Languages: eng Pagination: 230-4 Citation Subset: IM |
Affiliation:
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Inotek Pharmaceuticals Corporation, Beverly, MA 01915, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blotting, Western Cell Line, Tumor DNA / metabolism DNA Damage Enzyme Activation Enzyme Inhibitors / pharmacology Epithelial Cells / metabolism Humans Hydrogen Peroxide / pharmacology Indoles / pharmacology Inflammation Leukocytes / enzymology*, metabolism Male Myocardial Infarction / metabolism* Myocardium / enzymology, pathology Poly(ADP-ribose) Polymerases / blood, metabolism* Precipitin Tests Rats Rats, Wistar Reperfusion Injury Time Factors |
| Grant Support | |
ID/Acronym/Agency:
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R01HL59266/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/INO 1001; 0/Indoles; 7722-84-1/Hydrogen Peroxide; 9007-49-2/DNA; EC 2.4.2.30/Poly(ADP-ribose) Polymerases |
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