There is strong evidence that eating foods rich in omega-3 fatty acids, such as some fish, plant-derived oils and nuts, or taking omega-3s as a dietary supplement reduces inflammation and lowers the risk of illness and death from cardiovascular and other inflammatory diseases, said Bruce A. Freeman, Ph.D., professor and chair of the Department of Pharmacology and Chemical Biology, Pitt School of Medicine, and one of the study's senior authors.
"What has been a provocative question for people familiar with these impressive clinical actions is how omega-3 fatty acids actually induce such beneficial pharmacological effects," he said. "This study has given us fresh and revealing perspective into that process."
In this study, also led by Pitt assistant professor Francisco J. Schopfer, Ph.D., the researchers examined metabolic byproducts of omega-3 fatty acids that are produced by activated macrophages, a type of immune cell that is always present in inflamed tissue, and discovered previously unknown biochemical mediators of inflammation.
Using a small molecule called beta-mercaptoethanol (BME) as a reactive bait, Chiara Cipollina, Ph.D., one of the study's lead authors and a post-doctoral student from Palermo, Italy's Ri.MED Foundation, "hooked" several derivatives of omega-3 fatty acids that were produced by immune cells. These derivatives were chemically modified to become electrophilic fatty acid oxidation products (EFOX), meaning they are attracted to electrons and therefore react with critical molecular targets in many different cell types.
By interacting with certain protein residues that have electrons available for chemical binding, these derivatives stimulate changes in cellular protein function and the genetic expression patterns of cells, resulting in a broad range of antioxidant and anti-inflammatory responses.
The research team found that an enzyme called cyclooxygenase-2 (COX-2), which is the molecular target of common drugs such as aspirin, ibuprofen and acetaminophen, mediates the transformation of omega-3 fatty acids into EFOX. Notably, cellular EFOX concentrations were significantly increased in the presence of aspirin, suggesting another mechanism for that drug's beneficial effects.
"There is a lot of evidence that supports minimizing inflammation as a fundamental therapy for many diseases," Dr. Freeman said. "Our new insights help explain in part the multitude of beneficial actions observed for both omega-3 fatty acids and aspirin, and the discovery of this new class of omega-3 fatty acid-derived anti-inflammatory mediators could point drug development activities in new and fruitful directions."
For example, drugs that, like aspirin, enhance the production of EFOX could be of value, or new agents might be synthesized that are able to induce anti-inflammatory signals that are similar to those induced by EFOX, he explained. Drs. Freeman and Schopfer and their drug discovery team now are working on some of these approaches.
The research team also included co-lead author Alison L. Groeger, Ph.D., Marsha P. Cole, Ph.D., Steven R. Woodcock, Ph.D., and Gustavo Bonacci, Ph.D., all of the Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine. Co-authors Tanja K. Rudolph, M.D., and Volker Rudolph, M.D., have since returned to their positions at the University Heart Center, Hamburg, Germany.
The study was funded by start-up support from the University of Pittsburgh School of Medicine and grants from the National Institutes of Health, the American Diabetes Association, and the Ri.MED Foundation.
About the University of Pittsburgh School of Medicine
As one of the nation's leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1997 and now ranks fifth in the nation, according to preliminary data for fiscal year 2008. Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region's economy. For more information about the School of Medicine, see www.medschool.pitt.edu.
Anita Srikameswaran | EurekAlert!
New application for acoustics helps estimate marine life populations
16.01.2018 | University of California - San Diego
Unexpected environmental source of methane discovered
16.01.2018 | University of Washington Health Sciences/UW Medicine
What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...
For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.
Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...
At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.
No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...
Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.
Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...
The oceans are the largest global heat reservoir. As a result of man-made global warming, the temperature in the global climate system increases; around 90% of...
08.01.2018 | Event News
11.12.2017 | Event News
08.12.2017 | Event News
17.01.2018 | Ecology, The Environment and Conservation
17.01.2018 | Physics and Astronomy
17.01.2018 | Awards Funding