Resveratrol Potentiates Vitamin D and Nuclear Receptor Signaling†
Journal of Cellular Biochemistry, DOI: 10.1002/jcb.25070
Angelika Dampf-Stone1,‡, Shane Batie1,2,‡, Marya Sabir1,‡, Elizabeth T. Jacobs3,4, Jamie H. Lee1, G. Kerr Whitfield2, Mark R. Haussler2 and Peter W. Jurutka1,2, pjurutka at asu.edu
1 School of Mathematical and Natural Sciences, Arizona State University, Glendale, AZ 85306
2 Department of Basic Medical Sciences, The University of Arizona, College of Medicine, Phoenix, AZ, 85004
3 University of Arizona Cancer Center, Tucson AZ, 85724
4 Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ, 85724
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 two-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.
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31 studies referenced this study as of Oct 2020
- Regulation of resveratrol biosynthesis in grapevine: new approaches for disease resistance? - 2019
- Effects of resveratrol on bone health in type 2 diabetic patients. A double-blind randomized-controlled trial - 2018
- Biological effects of combined resveratrol and vitamin D3 on ovarian tissue - 2017
- Biological Effects of Vitamin D3 Mediated by the Interaction with VDR in Different Tissues
- EFFECTS OF RESVERATROL AND QUERCETIN ON VITAMIN D METABOLIZING CYTOCHROME P450 ENZYMES - 2016
See also Vitamin D Life
- Resveratrol category has
35 items along with related searches - Resveratrol improves health (Vitamin D receptor, etc.)
- Immune system improvement by vitamin D is boosted by resveratrol and blueberries – Sept 2013
- Vitamin D and Resveratrol reduce weight gain in rats - Sept 2011
- Resveratrol gets vitamin D to cells even if poor vitamin D receptor
- Decrease of Alzheimer’s biomarker halted by Resveratrol (perhaps due to vitamin D) – RCT Sept 2015
- Bone density improved with resveratrol (which improves Vitamin D Receptor) – RCT Sept 2018
VitaminDwiki updated the following chart due to this and previous Resveratrol studies
See also web
- Health Benefits and Molecular Mechanisms of Resveratrol: A Narrative Review - March 2020
- Extensive   PDF
- Top 16 Benefits of Resveratrol Self Hacked Dec 2018
Typically 5 mg/kg of body weight = 400 mg - Resveratrol supplementation, where are we now and where should we go? - May 2015
- Huge amount of variabiity in how much each person needs.
- Vitamin D Receptor is not mentioned
-  Download the PDF from Vitamin D Life
- Search PubMed for Resveratrol "vitamin D receptor" 346 items as of Feb 2020
- Nanotechnology-based formulations for resveratrol delivery: Effects on resveratrol in vivo bioavailability and bioactivity - Aug 2019 https://doi.org/10.1016/j.colsurfb.2019.04.030
- 2020 Top Resveratrol Supplements Guide: What To Avoid Society Health
- Does not appear to consider bio-availability
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