Mitochondrial-to-nuclear translocation of apoptosis-inducing factor in cardiac myocytes during oxidant stress: Potential role of poly(ADP-ribose) polymerase-1

Min Chen, Zsuzsanna Zsengellér, Chun Yang Xiao, Csaba Szabó

    Research output: Contribution to journalArticlepeer-review

    68 Scopus citations

    Abstract

    Objective: Oxidant stress-induced activation of poly(ADP-ribose) polymerase (PARP) plays a role in the pathogenesis of various cardiovascular diseases. We have now investigated the role of PARP in the death of cardiac myocytes in response to oxidant stress induced by hydrogen peroxide, with focus on the mitochondrial function. Methods and results: Using wild-type and PARP-1-deficient murine myocytes challenged with hydrogen peroxide, we found that mitochondrial respiration and mitochondrial membrane potential were better preserved in PARP-deficient myocytes and cellular NAD+ levels were maintained. The release of the mitochondrial cell death factor cytochrome c, and the mitochondrial-to-nuclear translocation of apoptosis-inducing factor (AIF) were also attenuated in the PARP-deficient myocytes. Conclusion: PARP-1, directly or indirectly, regulates the translocation of AIF in myocytes subjected to oxidative stress. The current results are consistent with the view that PARP-1 activation, via induction of mitochondrial dysfunction and promotion of mitochondrial cell death pathways, plays a deleterious pathophysiological role under conditions of oxidative stress.

    Original languageEnglish (US)
    Pages (from-to)682-688
    Number of pages7
    JournalCardiovascular research
    Volume63
    Issue number4
    DOIs
    StatePublished - Sep 1 2004

    Keywords

    • Apoptosis
    • DNA
    • Heart
    • Necrosis
    • Oxidative stress

    ASJC Scopus subject areas

    • Physiology
    • Cardiology and Cardiovascular Medicine
    • Physiology (medical)

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