Myocardial Ischemic Preconditioning in Rodents Is Dependent on Poly (ADP-Ribose) Synthetase

Lucas Liaudet, Zequan Yang, El Bachir Al-Affar, Csaba Szabo

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Background: Activation of the nuclear enzyme poly (ADP-ribose) synthetase (PARS) in response to oxidant-mediated DNA injury has been shown to play an important role in the pathogenesis of reperfusion injury. Here we investigated the role of PARS in myocardial ischemic preconditioning (IPC). Materials and Methods: Mice with or without genetic disruption of PARS and rats in the absence or presence of the PARS inhibitor 3-aminobenzamide underwent coronary occlusion and reperfusion with or without IPC. Results: Both poly(ADP-ribose) synthetase (PARS) deficiency and ischemic preconditioning (IPC) induced protection from reperfusion injury, attenuated inflammatory mediator production, and reduced neutrophil infiltration when compared to the response in wild-type mice. Surprisingly, the protective effect of IPC not only disappeared in PARS -/ mice, but the degree of myocardial injury and inflammatory response was similar to the one seen in wild-type animals. Similarly, in the rat model of IPC, 3-aminobenzamide pretreatment blocked the beneficial effect of IPC. Myocardial NAD+ levels were maintained in the PARS-deficient mice during reperfusion, while depleted in the wild-type mice. The protection against reperfusion injury by IPC was also associated with partially preserved myocardial NAD+ levels, indicating that PARS activation is attenuated by IPC. This conclusion was further strengthened by poly(ADP-ribose) immunohistochemical measurements, demonstrating that IPC markedly inhibits PARS activation during reperfusion. Conclusions: The mode of IPC's action is related, at least in part, to an inhibition of PARS. This process may occur either by self-auto-ribosylation of PARS during IPC, and/or via the release of endogenous purines during IPC that inhibit PARS activation during reperfusion.

Original languageEnglish (US)
Pages (from-to)406-417
Number of pages12
JournalMolecular Medicine
Volume7
Issue number6
StatePublished - 2001
Externally publishedYes

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Myocardial Ischemic Preconditioning
Poly Adenosine Diphosphate Ribose
Ligases
Ischemic Preconditioning
Rodentia
Reperfusion Injury
Reperfusion
NAD
Purines
Myocardial Reperfusion
Enzyme Activation
Wild Animals
Neutrophil Infiltration
Coronary Occlusion
Oxidants

ASJC Scopus subject areas

  • Genetics

Cite this

Liaudet, L., Yang, Z., Al-Affar, E. B., & Szabo, C. (2001). Myocardial Ischemic Preconditioning in Rodents Is Dependent on Poly (ADP-Ribose) Synthetase. Molecular Medicine, 7(6), 406-417.

Myocardial Ischemic Preconditioning in Rodents Is Dependent on Poly (ADP-Ribose) Synthetase. / Liaudet, Lucas; Yang, Zequan; Al-Affar, El Bachir; Szabo, Csaba.

In: Molecular Medicine, Vol. 7, No. 6, 2001, p. 406-417.

Research output: Contribution to journalArticle

Liaudet, L, Yang, Z, Al-Affar, EB & Szabo, C 2001, 'Myocardial Ischemic Preconditioning in Rodents Is Dependent on Poly (ADP-Ribose) Synthetase', Molecular Medicine, vol. 7, no. 6, pp. 406-417.
Liaudet, Lucas ; Yang, Zequan ; Al-Affar, El Bachir ; Szabo, Csaba. / Myocardial Ischemic Preconditioning in Rodents Is Dependent on Poly (ADP-Ribose) Synthetase. In: Molecular Medicine. 2001 ; Vol. 7, No. 6. pp. 406-417.
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