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

Jon Mabley, R. Wallace, P. Pacher, K. Murphy, C. Szabo

Research output: Contribution to journalArticleResearchpeer-review

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 anti-inflammatory 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-dihydroxy-vitamin 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
Pages (from-to)947-952
Number of pages6
JournalInternational Journal of Molecular Medicine
Volume19
Issue number6
Publication statusPublished - Jun 2007

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

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Mabley, Jon ; Wallace, R. ; Pacher, P. ; Murphy, K. ; Szabo, C. / 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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Inhibition of poly(adenosine diphosphate-ribose) polymerase by the active form of vitamin D. / Mabley, Jon; Wallace, R.; Pacher, P.; Murphy, K.; Szabo, C.

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

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

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AU - Mabley, Jon

AU - Wallace, R.

AU - Pacher, P.

AU - Murphy, K.

AU - Szabo, C.

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AB - Vitamin D is well characterized for its role in mineral homeostasis and maintenance of normal skeletal architecture. Vitamin D has been demonstrated to exert anti-inflammatory 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-dihydroxy-vitamin 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.

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