Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

U Iowa study identifies damaging mechanism in transplants and heart attacks

02.03.2004


A University of Iowa study suggests that inhibiting a certain protein involved in inflammation might be of therapeutic benefit in organ transplantation, heart attacks and possibly stroke. The study, led by John Engelhardt, Ph.D., UI professor and interim head of anatomy and cell biology, found that blocking the action of this protein can prevent the tissue damage caused by ischemia/reperfusion injury. The study is published in the March 1 issue of the Journal of Clinical Investigation.


John F. Engelhardt, Ph.D.



Ischemia/reperfusion injury is a common, damaging component of organ transplantation, heart attack, and stroke and is a determinant of organ failure in all cases. In this type of injury, the organ is initially deprived of oxygen-carrying blood (ischemia). During reperfusion (the re-establishment of blood supply), toxins are briefly generated from the oxygen that lead to tissue damage and trigger a potentially detrimental inflammatory response.

Although inflammation is an important bodily response to environmental injuries including bacterial and viral infection as well as ischemia/reperfusion injury, too much inflammation can damage healthy tissue and cause problems.


"In this study we looked at a well-known ’master switch’ type of protein called NF-kB that controls the expression of genes that regulate inflammatory responses," said Engelhardt, who also is professor of internal medicine in the UI Roy J. and Lucille A. Carver College of Medicine and director of the UI Center for Gene Therapy of Cystic Fibrosis and Other Genetic Diseases.

Engelhardt and his colleagues, including graduate student and lead author of the study, Chenguang Fan, compared the activation of NF-kB in response to bacterial infection and ischemia/ reperfusion injury. Historically, these two types of injury were thought to produce inflammation via the same cellular pathway. However, the UI researchers found that there are two distinct pathways for the two different types of injury.

"Important health implications have emerged from these studies, which may aid us in treating environmental injuries that have both ischemic and inflammatory components. We can now selectively remove, like a molecular surgeon, activation of one or both of these pathways using gene therapy approaches," Engelhardt said. "We found that selective inhibition of the pathway triggered by ischemia/reperfusion injury was better for the organ and better for the animal."

Activation of NF-kB is tightly controlled by so-called inhibitory proteins. Two of these inhibitory proteins, IkB alpha and IkB beta, keep NF-kB in an inactive state. However, injury leads to modification of the inhibitory proteins, causing them to release NF-kB. The activated master switch protein can then regulate expression of genes that mount a response to the injury.

The UI team used gene manipulation to replace IkB alpha with IkB beta in mice. Mice with only IkB beta protein respond to bacterial infection in the same way that normal mice do. However, these mice sustain less liver damage and were more likely to survive ischemic/reperfusion injury to that organ than mice with both inhibitory proteins.

The study found that the two inhibitory proteins function similarly in response to bacterial infection, but have different abilities to activate NF-kB after ischemia/reperfusion injury. Furthermore, the results suggest that inhibiting the IkB alpha pathway could prevent ischemic/reperfusion injury to transplanted organs and therefore improve the success of this procedure.

Similarly, Engelhardt speculated that blocking this pathway in patients at risk of a heart attack - a patient undergoing angioplasty, for example – potentially could benefit those patients in the event of a heart attack.

In addition to the animal experiments, the UI team also used gene therapy to manipulate the activation of NF-kB. These experiments helped reveal the different molecular pathways that activate NF-kB as a result of different types of injury.

"Gene therapy was a tool we used to address the mechanism of the disease process. But once you understand the process, those gene therapy tools become potential therapeutic tools," Engelhardt added. "This research has led to a better understanding of the disease process that occurs following ischemic/ reperfusion injury and a better understanding will allow us to potentially prevent or treat ischemic organ injury disorders."

In addition to Engelhardt and Fan, the research team also included Qiang Li, Yulong Zhang, Xiaoming Liu, D.V.M., Ph.D., Meihui Luo, Duane Abbott and Weihong Zhou, M.D. The research was supported by grants from the National Institutes of Health.

University of Iowa Health Care describes the partnership between the UI Roy J. and Lucille A. Carver College of Medicine and UI Hospitals and Clinics and the patient care, medical education and research programs and services they provide. Visit UI Health Care online at http://www.uihealthcare.com.


STORY SOURCE: University of Iowa Health Science Relations, 5135 Westlawn, Iowa City, Iowa 52242-1178

CONTACT(S): Jennifer Brown, 319-335-9917, jennifer-l-brown@uiowa.edu

PHOTOS/GRAPHICS: A photo of Dr. Engelhardt is available at http://www.anatomy.uiowa.edu/pages/directory/faculty/engelhardt.html

Jennifer Brown | EurekAlert!
Further information:
http://www.uiowa.edu/
http://www.anatomy.uiowa.edu/pages/directory/faculty/engelhardt.html

More articles from Health and Medicine:

nachricht Researchers release the brakes on the immune system
18.10.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht Norovirus evades immune system by hiding out in rare gut cells
12.10.2017 | 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: Neutron star merger directly observed for the first time

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...

Im Focus: Breaking: the first light from two neutron stars merging

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....

Im Focus: Smart sensors for efficient processes

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...

Im Focus: Cold molecules on collision course

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...

Im Focus: Shrinking the proton again!

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...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Terahertz spectroscopy goes nano

20.10.2017 | Information Technology

Strange but true: Turning a material upside down can sometimes make it softer

20.10.2017 | Materials Sciences

NRL clarifies valley polarization for electronic and optoelectronic technologies

20.10.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>