Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Enzyme found in blood vessels likely target to treat lung injury

30.04.2003


Lung injury due to infection, such as in sepsis, accounts for hundreds of thousands of hospitalizations a year. Sepsis occurs in 2 percent of hospital admissions and is associated with a death rate of about 50 percent. Many of these patients require ventilation to support their breathing, which may in itself produce additional injury to the lung. Yet, there are few available treatments for lung injury associated with sepsis or ventilation.



Now, scientists at Northwestern University have demonstrated that an enzyme vital to normal function of blood vessels also can be an Achilles heel during infection-induced or ventilator-induced lung injury. They believe that the enzyme holds significant potential as a drug discovery target for the treatment of acute lung injury.

As described in the May issue of Proceedings of the National Academy of Sciences, Mark Wainwright, M.D., and D. Martin Watterson identified a molecule, called myosin light chain kinase 210 (MLCK 210), that makes endothelial cells in the lung susceptible to injury during periods of inflammation.


Wainwright is assistant professor of pediatrics at the Feinberg School of Medicine at Northwestern University and a researcher at the Children’s Memorial Institute for Education and Research. Watterson is J.G. Searle Professor of Molecular Biology and Biochemistry, professor of molecular pharmacology and biological chemistry at the Feinberg School and director of the Northwestern University Drug Discovery Training Program.

Endothelial cells line blood vessels throughout the body and serve as a barrier to keep toxins in the blood from entering tissues and organs. MLCK 210 regulates normal endothelial cell function, but the contribution of MLCK 210 to the mechanisms of lung injury in the living animal was unknown.

Wainwright said that cell culture (or, in vitro) studies have identified several enzymes, including MLCK 210, in the regulation of endothelial barrier function, but no one had integrated the in vitro studies with disease injury and MLCK 210 function in a living animal.

Watterson genetically engineered mice that are missing the gene that codes for MLCK 210. The researchers exposed mice lacking MLCK 210 to a bacterial toxin that causes tissue injury as a result of severe infection. The MLCK 210 knockout mice are less susceptible to acute lung injury and also showed significant improvement in survival when exposed to a combination of toxin exposure and subsequent ventilator-induced injury.

This sequential injury is reminiscent of the clinical situation with life support for a critically ill patient.

The researchers also developed an MLCK inhibitor, an experimental drug that blocks the function of the enzyme, which they injected into normal mice with an intact MLCK 210 gene.

Normal mice exposed to bacterial toxin and ventilator-induced injury were protected by a single injection of the MLCK 210 inhibitor, a finding identical to that in the genetically altered mice lacking the MLCK 210 gene.

The researchers believe that their results and will enable scientists to conduct further studies involving the role of endothelial cells in heart disease, stroke and neurodegeneration, areas that the National Institutes of health has identified as a key research priority.

Co-authors were Janet Rossi; James Schavocky; Susan Crawford; David Steinhorn; Anastasia V. Velentza; Magdalena Zasadzki; Vladimir Shirinsky; Yuzhi Jia; Jacques Haiech; and Linda Van Eldik.

Elizabeth Crown | EurekAlert!
Further information:
http://www.nwu.edu/

More articles from Health and Medicine:

nachricht New study points the way to therapy for rare cancer that targets the young
22.11.2017 | Rockefeller University

nachricht Penn study identifies new malaria parasites in wild bonobos
21.11.2017 | University of Pennsylvania School of Medicine

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Frictional Heat Powers Hydrothermal Activity on Enceladus

Computer simulation shows how the icy moon heats water in a porous rock core

Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Underwater acoustic localization of marine mammals and vehicles

23.11.2017 | Information Technology

Enhancing the quantum sensing capabilities of diamond

23.11.2017 | Physics and Astronomy

Meadows beat out shrubs when it comes to storing carbon

23.11.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>