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 journalArticlepeer-review

41 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
DOIs
StatePublished - Jun 2007
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Genetics

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