BCL-2 protects peroxynitrite-treated thymocytes from poly(ADP-ribose) synthase (PARS)-independent apoptotic but not from PARS-mediated necrotic cell death

László Virág, Csaba Szabó

    Research output: Contribution to journalArticle

    28 Scopus citations

    Abstract

    In thymocytes, peroxynitrite induces poly(ADP-ribose) synthetase (PARS) activation, which results in necrotic cell death. In the absence of PARS, however, peroxynitrite-treated thymocytes die by apoptosis. Because Bcl-2 has been reported to inhibit not only apoptotic but also some forms of necrotic cell death, here we have investigated how Bcl-2 regulates the peroxynitrite-induced apoptotic and necrotic cell death. We have found that Bcl-2 did not provide protection against peroxynitrite-induced necrotic death, as characterized by propidium iodide uptake, mitochondrial membrane potential decrease, secondary superoxide production, and cardiolipin loss. In the presence of a PARS inhibitor, peroxynitrite-treated thymocytes from Bcl-2 transgenic mice showed no caspase activation or DNA fragmentation and displayed smaller mitochondrial membrane potential decrease. These data show that Bcl-2 protects thymocytes from peroxynitrite-induced apoptosis at a step proximal to mitochondrial alterations but fails to prevent PARS-mediated necrotic cell death. Activation of tissue transglutaminase (tTG) occurs in various forms of apoptosis. Peroxynitrite did not induce transglutaminase activity in thymocytes and did not have a direct inhibitory effect on the purified tTG. Basal tTG was not different in Bcl-2 transgenic and wild type cells. Copyright (C) 2000 Elsevier Science Inc.

    Original languageEnglish (US)
    Pages (from-to)704-713
    Number of pages10
    JournalFree Radical Biology and Medicine
    Volume29
    Issue number8
    DOIs
    StatePublished - Oct 15 2000

    Keywords

    • Apoptosis
    • Bcl-2
    • Free radicals
    • Necrosis
    • Peroxynitrite
    • Poly(ADP-ribose) synthetase
    • Transglutaminase

    ASJC Scopus subject areas

    • Biochemistry
    • Physiology (medical)

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