Peroxynitrite Causes Energy Depletion and Increases Permeability via Activation of Poly (ADP-Ribose) Synthetase in Pulmonary Epithelial Cells

Csaba Szabó, Christine Saunders, Michael O'Connor, Andrew L. Salzman

    Research output: Contribution to journalArticlepeer-review

    85 Scopus citations

    Abstract

    Recent studies show that peroxynitrite is a potent trigger of DNA strand breakage, which in turn activates the nuclear repair enzyme poly (ADP-ribose) synthetase (PARS), resulting in a cellular energy deficit. Here we present evidence that treatment of A549 human pulmonary epithelial cells with peroxynitrite (1 mM) results in ADP-ribosylation, NAD+ depletion, inhibition of mitochondrial respiration, and increased epithelial paracellular permeability. The PARS inhibitor 3-aminobenzamide (1 mM) provided a significant, partial protection against the energetic and functional changes. Similarly, inhibition of PARS activity by 3-aminobenzamide reduced the peroxynitrite-induced suppression of mitochondrial respiration in BEAS-2B human bronchial epithelial cells. Thus, PARS activation and energy depletion represents one of the pathways of peroxynitrite-mediated epithelial toxicity. Inhibition of PARS may improve cellular energy homeostasis in pathophysiologic conditions associated with peroxynitrite generation.

    Original languageEnglish (US)
    Pages (from-to)105-109
    Number of pages5
    JournalAmerican journal of respiratory cell and molecular biology
    Volume16
    Issue number2
    DOIs
    StatePublished - Jan 1 1997

    ASJC Scopus subject areas

    • Molecular Biology
    • Pulmonary and Respiratory Medicine
    • Clinical Biochemistry
    • Cell Biology

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