Document Detail

Activation of poly(ADP-ribose) polymerase in circulating leukocytes during myocardial infarction.
MedLine Citation:
PMID:  14770035     Owner:  NLM     Status:  MEDLINE    
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.
Kanneganti G K Murthy; Chun-Yang Xiao; Jon G Mabley; Min Chen; Csaba Szabó
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Shock (Augusta, Ga.)     Volume:  21     ISSN:  1073-2322     ISO Abbreviation:  Shock     Publication Date:  2004 Mar 
Date Detail:
Created Date:  2004-02-10     Completed Date:  2004-10-19     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9421564     Medline TA:  Shock     Country:  United States    
Other Details:
Languages:  eng     Pagination:  230-4     Citation Subset:  IM    
Inotek Pharmaceuticals Corporation, Beverly, MA 01915, USA.
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MeSH Terms
Blotting, Western
Cell Line, Tumor
DNA / metabolism
DNA Damage
Enzyme Activation
Enzyme Inhibitors / pharmacology
Epithelial Cells / metabolism
Hydrogen Peroxide / pharmacology
Indoles / pharmacology
Leukocytes / enzymology*,  metabolism
Myocardial Infarction / metabolism*
Myocardium / enzymology,  pathology
Poly(ADP-ribose) Polymerases / blood,  metabolism*
Precipitin Tests
Rats, Wistar
Reperfusion Injury
Time Factors
Grant Support
Reg. No./Substance:
0/Enzyme Inhibitors; 0/INO 1001; 0/Indoles; 7722-84-1/Hydrogen Peroxide; 9007-49-2/DNA; EC Polymerases

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