Researchers at the University of Pennsylvania School of Medicine and Queen's University, Ontario, Canada report in the online edition of Nature Medicine this week that the COX enzymes – well-known for their contrasting role in cardiovascular biology – interact physically to form a previously unrecognized biochemical partnership and function in the development of blood vessels in a mouse model. Collaborators Garret FitzGerald, MD, Director of Penn's Institute for Translational Medicine and Therapeutics, and Colin Funk from Queen's University, say that the findings suggest new biological, developmental, and therapeutic roles for COX enzymes and prompt a re-evaluation of basic assumptions about the role of COX enzymes in disease.
COX-2 is the target of the now familiar COX inhibitors Vioxx and Celebrex. COX-1, the less celebrated sister, is the target of low-dose aspirin and older drugs, such as Advil and Naprosyn, which inhibit both COX-1 and COX-2 to prevent heart disease.
Researchers have known for some time that COX-1 and COX-2 pair up to function in the body. Even though they are interlocked, only one of them is active at a time in processing their substrate, arachidonic acid – from which prostaglandins, the fatty mediators of pain, inflammation, and heart attacks – are formed. The molecular structures of COX-1 and COX-2 are remarkably similar, but a subtle variation in their structure permits the construction of drugs that are selective in their inhibition for COX -2.
For this study the researchers developed a novel genetic mouse model that mimics the physiology of COX-2 inhibition. The investigators demonstrated that the COX-1:COX-2 partnership, or heterodimer, appears to play a critical role in the transformation that occurs in the blood vessels of newly born mice, shortly after birth, namely the closing of the ductus arterious. This necessary developmental step permits newborns to function independently from their mother.
"These observations prompt us to explore new roles for the COX enzymes in biology," says FitzGerald. "Perhaps their embrace will extend to other enzymes, such as the lipoxygenases and the nitric oxide synthases, in ways that prompt us to re-evaluate basic assumptions about the role of COX enzymes in physiology and disease."
"Perhaps this combination of COX enzymes will represent a new drug target," speculates Funk. "Blocking the COX dimer may alter the pattern of usefulness and/or safety that we associate with existing non-steroidal anti-inflammatory drugs." Funk, who has collaborated with FitzGerald at Penn over the last decade on this line of research, is now the Canada Research Chair of Physiology at Queen's University, Ontario.
Karen Kreeger | EurekAlert!
Individual Receptors Caught at Work
19.10.2017 | Julius-Maximilians-Universität Würzburg
Rapid environmental change makes species more vulnerable to extinction
19.10.2017 | Universität Zürich
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
19.10.2017 | Materials Sciences
19.10.2017 | Materials Sciences
19.10.2017 | Physics and Astronomy