We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress hp
Sign In
Advertise with Us
INTEGRA BIOSCIENCES AG

Download Mobile App




Low Doses of Resveratrol Activate Stress-lowering Molecular Pathway

By LabMedica International staff writers
Posted on 04 Jan 2015
Print article
Image: Three-dimensional molecular space-fill model of resveratrol (Photo courtesy of Wikimedia Commons).
Image: Three-dimensional molecular space-fill model of resveratrol (Photo courtesy of Wikimedia Commons).
A molecular mechanism has been identified that explains how the wine and grape product resveratrol modulates the inflammatory response by interacting with the enzyme tyrosyl transfer-RNA (tRNA) synthetase (TyrRS).

Resveratrol (trans-3,5,4'-trihydroxystilbene), a compound found largely in the skins of red grapes, is a component of Ko-jo-kon, a form of oriental medicine used to treat diseases of the blood vessels, heart, and liver. Red wine contains between 0.2 and 5.8 milligrams per liter of resveratrol, depending on the grape variety, while white wine has much less, the reason being that red wine is fermented with the skins, allowing the wine to absorb the resveratrol, whereas white wine is fermented after the skin has been removed. Resveratrol came to scientific attention during the mid-1990s as a possible explanation for the "French Paradox,” the low incidence of heart disease among the French, who eat a relatively high-fat diet. Since then, it has been promoted by manufacturers and examined by scientific researchers as an antioxidant, an anticancer agent, and a phytoestrogen.

Investigators at The Scripps Research Institute (La Jolla, CA, USA) had been studying TyrRS, which moves into the nucleus under stress conditions. In light of the stress-related benefits of resveratrol, they considered the possibility that the tyrosine-like phenolic ring of resveratrol might fit into the active site pocket of TyrRS to induce the enzyme's nuclear role.

To examine this possibility they used X-ray crystallography to generate a 2.1 Angstrom co-crystal structure of resveratrol bound to the active site of TyrRS. The results, which were published in the December 22, 2014, online edition of the journal Nature, revealed that resveratrol nullified the catalytic activity of the enzyme and redirected it to a nuclear function. In the nucleus the enzyme stimulated NAD+-dependent auto-poly-ADP-ribosylation of poly(ADP-ribose) polymerase 1 (PARP-1). PARP-1 is a major stress response and DNA-repair factor that is thought to have a significance influence on lifespan.

The TyrRS/resveratrol interaction was confirmed in a mouse model. Injection of resveratrol led to activation of PARP-1 by TyrRS with subsequent activation of several protective genes including the tumor-suppressor gene p53 and the longevity genes FOXO3A and SIRT6. PARP-1 activation could be specifically blocked in vivo by a resveratrol-displacing tyrosyl adenylate analogue.

The results indicated that the TyrRS-PARP-1 pathway could be measurably activated by much lower doses of resveratrol - as much as 1,000 times lower -than had been used in some prior studies, including those focused on SIRT1.

“This stress response represents a layer of biology that has been largely overlooked, and resveratrol turns out to activate it at much lower concentrations than those used in prior studies,” said senior author Dr. Paul Schimmel, professor of chemical biology at The Scripps Research Institute. “We think this is just the tip of the iceberg. We think there are a lot more amino-acid mimics out there that can have beneficial effects like this in people. And we are working on that now.”

Related Links:
The Scripps Research Institute


Gold Member
Fully Automated Cell Density/Viability Analyzer
BioProfile FAST CDV
Unit-Dose Packaging solution
HLX
New
Urine Collection Container
Urine Monovette
New
Gold Member
ANA & ENA Screening Assays
ANA and ENA Assays

Print article

Channels

Clinical Chemistry

view channel
Image: The new saliva-based test for heart failure measures two biomarkers in about 15 minutes (Photo courtesy of Trey Pittman)

POC Saliva Testing Device Predicts Heart Failure in 15 Minutes

Heart failure is a serious condition where the heart muscle is unable to pump sufficient oxygen-rich blood throughout the body. It ranks as a major cause of death globally and is particularly fatal for... Read more

Molecular Diagnostics

view channel
Image: The bowel cancer breakthrough could result in better treatment outcomes (Photo courtesy of 123RF)

New RNA Molecules Can Help Predict Bowel Cancer Return Recurrence

Colorectal cancer accounts for 10% of all cancer-related deaths worldwide and was ranked as the second most common cause of cancer death in the United States in 2022. Currently, clinicians face diagnostic... Read more

Hematology

view channel
Image: QScout CBC will give a complete blood count in 2 minutes from fingerstick or venous blood (Photo courtesy of Ad Astra Diagnostics)

Next Gen CBC and Sepsis Diagnostic System Targets Faster, Earlier, Easier Results

Every hour is critical in protecting patients from infections, yet there are currently limited tools to assist in early diagnosis before patients reach a hospital. The complete blood count (CBC) is a common... Read more

Microbiology

view channel
Image: The InfectoSynovia test has the potential to revolutionize the diagnosis of periprosthetic joint infection (Photo courtesy of 123RF)

High-Accuracy Bedside Test to Diagnose Periprosthetic Joint Infection in Five Minutes

Periprosthetic joint infection (PJI) represents a significant global issue that is worsening as the number of joint replacements increases due to aging populations. In the United States alone, the anticipated... Read more

Pathology

view channel
Image

AI-Based Method Shows Promise for Pathological Diagnosis of Hereditary Kidney Diseases

Alport syndrome is a hereditary kidney disorder characterized by kidney dysfunction, sensorineural hearing loss, and ocular abnormalities. Early in the disease, patients experience hematuria, which is... Read more
Copyright © 2000-2024 Globetech Media. All rights reserved.