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

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

Research output: Contribution to journalArticle

30 Citations (Scopus)

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 2007
Externally publishedYes

Fingerprint

Poly Adenosine Diphosphate Ribose
Vitamin D
Calcitriol
Anti-Inflammatory Agents
Keratinocytes
Sunlight
Inflammatory Bowel Diseases
Cytochrome P-450 Enzyme System
Arthritis
Minerals
Homeostasis
Maintenance
Pharmacology

Keywords

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

ASJC Scopus subject areas

  • Genetics

Cite this

Inhibition of poly(adenosine diphosphate-ribose) polymerase by the active form of vitamin D. / Mabley, Jon G.; Wallace, Rebecca; Pacher, Pál; Murphy, Kanneganti; Szabo, Csaba.

In: International Journal of Molecular Medicine, Vol. 19, No. 6, 06.2007, p. 947-952.

Research output: Contribution to journalArticle

Mabley, Jon G. ; Wallace, Rebecca ; Pacher, Pál ; Murphy, Kanneganti ; Szabo, Csaba. / Inhibition of poly(adenosine diphosphate-ribose) polymerase by the active form of vitamin D. In: International Journal of Molecular Medicine. 2007 ; Vol. 19, No. 6. pp. 947-952.
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