Nitric oxide-peroxynitrite-poly(ADP-ribose) polymerase pathway in the skin

László Virág, Éva Szabó, Edina Bakondi, Péter Bai, Pál Gergely, János Hunyadi, Csaba Szabó

    Research output: Contribution to journalReview article

    65 Scopus citations

    Abstract

    In the last decade it has become well established that in the skin, nitric oxide (NO), a diffusable gas, mediates various physiologic functions ranging from the regulation of cutaneous blood flow to melanogenesis. If produced in excess, NO combines with superoxide anion to form peroxynitrite (ONOO-), a cytotoxic oxidant that has been made responsible for tissue injury during shock, inflammation and ischemia-reperfusion. The opposite effects of NO and ONOO- on various cellular processes may explain the 'double-edged sword' nature of NO depending on whether or not cellular conditions favour peroxynitrite formation. Peroxynitrite has been shown to activate the nuclear nick sensor enzyme, poly(ADP-ribose) polymerase (PARP). Overactivation of PARP depletes the cellular stores of NAD+, the substrate of PARP, and the ensuing 'cellular energetic catastrophy' results in necrotic cell death. Whereas the role of NO in numerous skin diseases including wound healing, burn injury, psoriasis, irritant and allergic contact dermatitis, ultraviolet (UV) light-induced sunburn erythema and the control of skin infections has been extensively documented, the intracutaneous role of peroxynitrite and PARP has not been fully explored. We have recently demonstrated peroxynitrite production, DNA breakage and PARP activation in a murine model of contact hypersensitivity, and propose that the peroxynitrite-PARP route represents a common pathway in the pathomechanism of inflammatory skin diseases. Here we briefly review the role of NO in skin pathology and focus on the possible roles played by peroxynitrite and PARP in various skin diseases.

    Original languageEnglish (US)
    Pages (from-to)189-202
    Number of pages14
    JournalExperimental dermatology
    Volume11
    Issue number3
    DOIs
    StatePublished - Jun 1 2002

    Keywords

    • Inflammation
    • Keratinocyte
    • Nitric oxide
    • Peroxynitrite
    • Poly(ADP-ribose) polymerase
    • Skin

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Dermatology

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  • Cite this

    Virág, L., Szabó, É., Bakondi, E., Bai, P., Gergely, P., Hunyadi, J., & Szabó, C. (2002). Nitric oxide-peroxynitrite-poly(ADP-ribose) polymerase pathway in the skin. Experimental dermatology, 11(3), 189-202. https://doi.org/10.1034/j.1600-0625.2002.110301.x