New Mechanism of Resveratrol Stress Response Described

Paul Schimmel, Ph.D. Professor The Skaggs Institute for Chemical Biology, The Scripps Laboratories for tRNA Synthetase Research Department of Molecular and Cell Biology, The Scripps Research Institute, La Jolla, California MedicalResearch.com Interview with:
Paul Schimmel, Ph.D. Professor
The Skaggs Institute for Chemical Biology,
The Scripps Laboratories for tRNA Synthetase Research
Department of Molecular and Cell Biology,
The Scripps Research Institute, La Jolla, California

Medical Research: What is the background for this study? What are the main findings?

Dr. Schimmel: Resveratrol (RSV) is thought to provide health benefits by activating a protective stress response. In the paper we described a new, previously missed mechanism for its action. This mechanism is activated at much lower concentrations of resveratrol than previously described or imagined. Consequently, other mechanisms, which appear to act at higher concentrations of resveratrol, are layered over a preexisting foundation set by the newly revealed mechanism.

Medical Research: What should clinicians and patients take away from your report?

Dr. Schimmel: Resveratrol may be active in humans at lower concentrations than previously thought. However, the bio-availabiliy is a limiting factor, and that is still an area of much investigation. RSV in grape skins is probably of little pharmacological benefit, because  it needs to be leeched out of the skins. In the fermentation process to produce wine, the resveratrol is released, and made more soluble by the alcohol content. The question is whether the new studies can support the idea that the newly revealed mechanism, working at much lower concentration of resveratrol, is activated from the resveratrol present in a couple of glasses of red wine. That is not known and being further considered.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Schimmel: We believe there are many more examples of plant-based compounds, some in the food chain, which trigger signaling pathways that are initiated through their binding to target proteins in the aminoacyl tRNA synthetase family. This family of proteins is amongst the most ancient, and appeared at the beginnings of life, and is universally distributed through all living organisms. In our study, the new mechanism was found to act through one of these family members. Other members, we believe, will also be seen to have special roles that are yet to be revealed. We are working on this idea.

Citation:

A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol
The Skaggs Institute for Chemical Biology, The Scripps Laboratories for tRNA Synthetase Research, Department of Molecular and Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037,

Nature (2014) doi:10.1038/nature14028 22 December 2014