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!
Single-stranded DNA and RNA origami go live
15.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard
New antbird species discovered in Peru by LSU ornithologists
15.12.2017 | Louisiana State University
DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.
Researchers have created chemical amplifiers and a chemical oscillator using a systematic method that has the potential to embed sophisticated circuit...
MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.
Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...
Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...
Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.
To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...
The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.
Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...
11.12.2017 | Event News
08.12.2017 | Event News
07.12.2017 | Event News
15.12.2017 | Power and Electrical Engineering
15.12.2017 | Materials Sciences
15.12.2017 | Life Sciences