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 Correct connections are crucial
26.06.2017 | Charité - Universitätsmedizin Berlin

nachricht One gene closer to regenerative therapy for muscular disorders
01.06.2017 | Cincinnati Children's Hospital Medical Center

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: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Study shines light on brain cells that coordinate movement

26.06.2017 | Life Sciences

Smooth propagation of spin waves using gold

26.06.2017 | Physics and Astronomy

Switchable DNA mini-machines store information

26.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>