Red wine compound activates stress response to promote health benefits

By now, most of us have heard of resveratrol - a compound found in red wine and grapes that has been linked to an array of health benefits, such as reduced risk of age-related diseases. Researchers have long investigated how resveratrol promotes such benefits. Now, scientists from The Scripps Research Institute in La Jolla, CA, offer a new suggestion; the compound stimulates a stress response gene, which activates a number of genes that protect the body.

Drinking two glasses of red wine can trigger the stress response that promotes numerous health benefits, according to the researchers.

The research team at the Skaggs Institute for Chemical Biology at The Scripps Research Institute (TSRI), published their findings in the journal Nature.

Past research has associated resveratrol with longevity and reduced risk of cardiovascular disease (CVD). 

Last year, another team of researchers reported on a study claiming the compound could help treat several cancers by sensitizing diseased cells to treatment, while another study claimed resveratrol can protect against hearing loss and cognitive decline.

More recently, however, some studies have blasted the health benefits of resveratrol. 

In May 2014, researchers from Johns Hopkins University School of Medicine in Baltimore, MD, claimed people who consume a diet rich in resveratrol are at no lower risk of CVD or cancer than those who consume small amounts of the compound.

Some researchers have questioned the health benefits of resveratrol because many studies have used "unrealistically high doses" of the compound.

In this latest study, the researchers set out to determine if resveratrol really is beneficial for health and if so, how the compound promotes such benefits.

Resveratrol binds to TyrRS enzyme to activate protective genes

The researchers investigated resveratrol's association with tRNA synthetases - enzymes that aid translation of genetic material during protein synthesis.

In particular, the researchers focused on a specific tRNA synthetase called TyrRS - an enzyme that binds with an amino acid called tyrosine before linking up with encoding genetic material - after a former investigator at TSRI found that it can relocate to the cell nucleus under stressful conditions, effectively adopting a protective role.

Since resveratrol has been shown to have similar properties to tyrosine and has been associated with a comparable stress response, Sajish says he wanted to see whether TyrRS is a target for the compound.

Using X-ray crystallography and other tests to compare resveratrol with TyrRS, the researchers found that resveratrol mimics tyrosine, so much so that TyrRS was able to bind with resveratrol. The team explains that this attachment led TyrRS away from its protein translation activity and pushed it toward the cell nucleus.

Once in the nucleus, the researchers found that the TyrRS-resveratrol combination switched on a gene called PARP-1 - known to play a role in stress response and DNA repair and to have a major influence on aging. What is more, activating PARP-1 also switched on a number of other protective genes, including FOXO3A and SIRT6 - associated with longevity - and the tumor-suppressor gene p53.

The team notes that their findings were confirmed when they injected mice with resveratrol.

'A couple of glasses of red wine' could evoke protective effect of resveratrol

Interestingly, the research team found that the TyrRS-PARP1 pathway can be activated with doses of resveratrol up to 1,000 times lower than doses that have been used in past studies investigating the compound's health benefits.

Based on these results, it is conceivable that moderate consumption of a couple glasses of red wine would give a person enough resveratrol to evoke a protective effect via this pathway:

"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.

With these findings we have a new, fundamental mechanism for the known beneficial effects of resveratrol."

The research team adds that because previous research has used such high doses of resveratrol, this may have confounded some results.

Resveratrol triggers a similar stress-response pathway in plant cells, according to the researchers, and they believe the compound has grown to produce a similar effect in human cells. We believe that TyrRS has evolved to act as a top-level switch or activator of a fundamental cell-protecting mechanism that works in virtually all forms of life.

References:

1.  A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol, Mathew Sajish, et al., Nature, doi:10.1038/nature14028, published online 22 December 2014, abstract.
2.  TSRI news release, accessed 23 December 2014 via AlphaGalileo.