Inhibition of poly(adenosine diphosphate-ribose) polymerase by the active form of vitamin D

Jon G. Mabley, Rebecca Wallace, Pál Pacher, Kanneganti Murphy, Csaba Szabó

    Research output: Contribution to journalArticle

    32 Scopus citations

    Abstract

    Vitamin D is well characterized for its role in mineral homeostasis and maintenance of normal skeletal architecture. Vitamin D has been demonstrated to exert antiinflammatory effects in a variety of disease states including diabetes, arthritis and inflammatory bowel disease. In these diseases poly[adenosine diphosphate (ADP)-ribose] polymerase (PARP) inhibitors have also proved effective as anti-inflammatory agents. Here we present data demonstrating that the active metabolite of vitamin D, 1α,25-dihydroxyvitamin D3, is a PARP inhibitor. UV irradiation-mediated PARP activation in human keratinocytes can be inhibited by treatment with vitamin D, 7-dehydrocholesterol or 1α,25-dihydroxyvitamin D3. Inhibition of cytochrome P450 reversed the PARP inhibitory action of vitamin D and 7-dehydrocholesterol, indicating that conversion to 1α,25-dihydroxyvitamin D3 mediates their PARP inhibitory action. Vitamin D may protect keratinocytes against over-activation of PARP resulting from exposure to sunlight. PARP inhibition may contribute to the pharmacological and anti-inflammatory effects of vitamin D.

    Original languageEnglish (US)
    Pages (from-to)947-952
    Number of pages6
    JournalInternational journal of molecular medicine
    Volume19
    Issue number6
    StatePublished - Jun 1 2007

    Keywords

    • 1α,25-dihydroxyvitamin D3
    • 7-dehydrocholesterol
    • Keratinocytes
    • Oxidative stress
    • Poly(adenosine diphosphate-ribose) polymerase

    ASJC Scopus subject areas

    • Genetics

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  • Cite this

    Mabley, J. G., Wallace, R., Pacher, P., Murphy, K., & Szabó, C. (2007). Inhibition of poly(adenosine diphosphate-ribose) polymerase by the active form of vitamin D. International journal of molecular medicine, 19(6), 947-952.