Activation of poly(ADP-ribose) polymerase in circulating leukocytes during myocardial infarction

K.G.K. Murthy, C.Y. Xiao, Jon Mabley, M. Chen, C. Szabo

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)230-234
Number of pages5
JournalShock
Volume21
Issue number3
DOIs
Publication statusPublished - Mar 2004

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Poly(ADP-ribose) Polymerases
Myocardial Reperfusion
Leukocytes
Myocardial Infarction
Myocardial Ischemia
Reperfusion Injury
Myocardial Reperfusion Injury
Single-Stranded DNA Breaks
Oxidants
Adenosine Diphosphate
Reperfusion
Ligation
Shock
Coronary Vessels
Oxidative Stress
Inflammation
Wounds and Injuries
Enzymes

Cite this

Murthy, K.G.K. ; Xiao, C.Y. ; Mabley, Jon ; Chen, M. ; Szabo, C. / Activation of poly(ADP-ribose) polymerase in circulating leukocytes during myocardial infarction. In: Shock. 2004 ; Vol. 21, No. 3. pp. 230-234.
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Activation of poly(ADP-ribose) polymerase in circulating leukocytes during myocardial infarction. / Murthy, K.G.K.; Xiao, C.Y.; Mabley, Jon; Chen, M.; Szabo, C.

In: Shock, Vol. 21, No. 3, 03.2004, p. 230-234.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Activation of poly(ADP-ribose) polymerase in circulating leukocytes during myocardial infarction

AU - Murthy, K.G.K.

AU - Xiao, C.Y.

AU - Mabley, Jon

AU - Chen, M.

AU - Szabo, C.

PY - 2004/3

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AB - 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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