Poly(ADP-ribose) polymerase inhibition prevents both apoptotic-like delayed neuronal death and necrosis after H2O2 injury

Kasie K. Cole, J. Regino Perez-Polo

    Research output: Contribution to journalArticle

    89 Scopus citations

    Abstract

    Toxic reactive oxygen species (ROS) such as hydrogen peroxide, nitric oxide, superoxide, and the hydroxyl radical are generated in a variety of neuropathological conditions and cause significant DNA damage. We determined the effects of 3-aminobenzamide (AB), an inhibitor of the DNA repair enzyme poly(ADP-ribose) polymerase (PARP), on cell death in differentiated PC12 cells, a model of sympathetic neurons, after H2O2 injury. Exposure to 0.5 mM H2O2 resulted in a significant decrease in intracellular NAD(H), NADP(H), and ATP levels. This injury resulted in the death of 90% of the cells with significant necrosis early (2 h) after injury and increased apoptosis (12-24 h after injury), as measured by PS exposure and the presence of cytoplasmic oligonudeosomal fragments. Treatment with 2.5 mM AB restored pyridine nudeotide and ATP levels and ameliorated cell death (65% versus 90%) by decreasing the extent of both necrosis and apoptosis. Interestingly, we observed that H2O2-induced injury caused a delayed cell death exhibiting features of apoptosis but in which caspase-3 like activity was absent. Moreover, pretreatment with AB restored caspase-3-like activity. Our results suggest that apoptosis and necrosis are both triggered by PARP overactivation, and that maintenance of cellular energy levels after injury by inhibiting PARP shifts cell death from necrosis to apoptosis.

    Original languageEnglish (US)
    Pages (from-to)19-29
    Number of pages11
    JournalJournal of neurochemistry
    Volume82
    Issue number1
    DOIs
    StatePublished - Jul 22 2002

    Keywords

    • Apoptosis
    • Necrosis
    • PC12
    • Poly(ADP-ribose) polymerase
    • Reactive oxygen species

    ASJC Scopus subject areas

    • Biochemistry
    • Cellular and Molecular Neuroscience

    Fingerprint Dive into the research topics of 'Poly(ADP-ribose) polymerase inhibition prevents both apoptotic-like delayed neuronal death and necrosis after H<sub>2</sub>O<sub>2</sub> injury'. Together they form a unique fingerprint.

  • Cite this