Resveratrol potentiates vitamin D and nuclear receptor signaling

Angelika Dampf Stone, Shane F. Batie, Marya S. Sabir, Elizabeth T. Jacobs, Jamie H. Lee, G. Kerr Whitfield, Mark R. Haussler, Peter W. Jurutka

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

The 1,25-dihydroxyvitamin D3 (1,25D) hormone is derived from vitamin D generated in skin or obtained from the diet, and binds to and activates the vitamin D receptor (VDR) in target tissues including kidney, colon/small intestine, and bone/muscle. We tested resveratrol for its ability to modulate VDR signaling, using vitamin D responsive element (VDRE) and mammalian 2-hybrid (M2H) transcriptional system technology. Via VDRE-based assays in kidney, colon and myoblast cells, VDR-mediated transcription was activated by resveratrol, and a cooperative effect on transactivation was observed with resveratrol plus 1,25D. The M2H assay revealed a modest, resveratrol-induced dimerization of VDR with its retinoid X receptor (RXR) heteropartner. Cells treated with both resveratrol and 1,25D displayed synergistic stimulation of VDR-RXR heterodimerization, while resveratrol antagonized rexinoid-mediated RXR-RXR homodimerization. Increased transactivation in response to resveratrol was also observed with a subset of other nuclear receptors and their respective cognate responsive elements. Evaluation of wild-type versus a ligand-binding domain mutant VDR revealed that hormone-responsiveness to 1,25D was severely depressed, while the response to resveratrol was only moderately attenuated. Moreover, radiolabeled 1,25D-displacement assays demonstrated an increase in VDR-bound 1,25D in the presence of resveratrol. Thus, resveratrol may affect VDR and other nuclear receptors indirectly, likely via the ability of resveratrol to: (1) potentiate 1,25D binding to VDR; (2) activate RXR; and/or (3) stimulate SIRT1, an enzyme known to deacetylate nuclear receptors. The results of this study elucidate a possible pathway for crosstalk between two nutritionally derived lipids, vitamin D and resveratrol, both of which converge on VDR signaling. J. Cell. Biochem. 116: 1130-1143, 2015.

Original languageEnglish (US)
Pages (from-to)1130-1143
Number of pages14
JournalJournal of Cellular Biochemistry
Volume116
Issue number6
DOIs
StatePublished - Jun 1 2015

Keywords

  • ACETYLATION
  • NUTRACEUTICAL
  • SIRT1
  • TRANSACTIVATION
  • VITAMIN D RECEPTOR

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Resveratrol potentiates vitamin D and nuclear receptor signaling'. Together they form a unique fingerprint.

  • Cite this