Navigation Links
Boosting blood system protein complex protects against radiation toxicity
Date:6/24/2012

CINCINNATI - New research in Nature Medicine shows that boosting a protein pathway in the body's blood making system protects mice from otherwise fatal radiation poisoning.

Scientists in the multi-institutional study posted online by the journal on June 24 say their findings open the potential for new treatments against radiation toxicity during cancer treatment or environmental exposures such as in a nuclear explosion or accident.

By identifying a target-specific intervention to protect the hematopoietic system against radiation toxicity, the study addresses a largely unmet challenge, according to the researchers.

"These findings suggest that pharmacologic augmentation of the activity of the Thbd-aPC pathway by recombinant Thbd (thrombomodulin) or aPC (activated protein C) might offer a rational approach to the mitigation of tissue injury and lethality caused by ionizing radiation," the scientists write in their manuscript. "Recombinant human aPC has undergone extensive clinical testing in patients, and recombinant soluble human Thbd is currently being investigated for efficacy in antithrombotic therapy in humans. Our data encourage the further evaluation of these proteins for their radio-mitigating activities."

The study reveals a previously unknown function of the Thbd-aPC pathway in radiation mitigation. The pathway is normally known for its ability to prevent the formation of blood clots and help the body fight infections. The researchers found the pathway helps blood cells in the bone marrow recover from injury caused by radiation exposure. They demonstrated that pharmacologic boosting of this pathway with two drugs tested for the treatment of thrombosis or infection (recombinant Thbd and aPC respectively) can be used in mice to prevent death caused by exposure to lethal doses of radiation.

In all instances of treatment with recombinant soluble Thbd or aPC, the result was accelerated recovery of hematopoietic progenitor cell activity in bone marrow and a reduction in the harmful effects of lethal total body irradiation. When treatment was with aPC, these benefits occurred even when treatment was delayed for 24 hours.

The scientists caution their study involves early laboratory research in mice, so it remains to be tested how the findings may translate to human treatment. Researchers also need to determine exactly why the protective function of the targeted Thbd-aPC protein pathway seems to work so well in mice.

Researchers noted that the protective benefits of Thbd-aPC occurred only in vivo in irradiated mouse models. The researchers reported that overexpressed Thbd in irradiated laboratory cell cultures did not offer the same protective benefits, as the cells did not survive. This indicates the protective benefits of Thbd on blood making cells in irradiated mouse models depends on the help of additional cells or molecules in the body, which the researchers are trying to identify in a follow-up study.

The study involves extensive multi-scientist collaborations that combined previously independent lines of research by groups at Cincinnati Children's Hospital Medical Center and the University of Ulm, Germany (led by Hartmut Geiger, PhD, Division of Experimental Hematology/Cancer Biology and the Department of Dermatology/Allergic Diseases); the University of Arkansas, Little Rock (led by Martin Hauer-Jensen, MD, PhD, Division of Radiation Health, the College of Pharmacy and the Central Arkansas Veterans Healthcare System); the Blood Research Institute in Milwaukee, Wis. (led by Hartmut Weiler, PhD); and The Scripps Research Institute in La Jolla, Calif. (led by John H. Griffin, PhD, Department of Molecular and Experimental Medicine).

The research team said the current study exemplifies a global shift to multi-investigator projects that allow a combination of varied expertise by scientists tackling complex problems from the perspective of their respective fields. This approach requires the willingness of investigators to share unpublished data and engage in an open collaboration. The researchers also said the study underscores the importance of continued federal funding for leading edge basic research that can benefit human health.


'/>"/>

Contact: Nick Miller
nicholas.miller@cchmc.org
513-803-6035
Cincinnati Children's Hospital Medical Center
Source:Eurekalert

Related biology news :

1. Stanford scientists develop gene therapy approach to grow blood vessels in ischemic limbs
2. Scientists produce eye structures from human blood-derived stem cells
3. Blood on the menu
4. Glycemic index foods at breakfast can control blood sugar throughout the day
5. Detecting breast cancers fingerprint in a droplet of blood
6. Second-generation drug used for hypertension aids heart function independent of blood pressure
7. Changes in brains blood flow could cause brain freeze
8. Leeches are DNA bloodhounds in the jungle
9. VolitionRX Raises Over $1 Million To Begin Clinical Trials of Blood Based Diagnostic Tests
10. New microscope uses rainbow of light to image the flow of individual blood cells
11. John Theurer Cancer Center presents significant blood cancer research at 2012 ASCO Annual Meeting
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/27/2016)... , June 27, 2016 Research and ... North America 2016-2020" report to their offering. ... North America to grow at a CAGR of ... been prepared based on an in-depth market analysis with inputs from ... prospects over the coming years. The report also includes a discussion ...
(Date:6/22/2016)... June 22, 2016  The American College of Medical Genetics ... Executive Magazine as one of the fastest-growing trade shows ... at the Bellagio in Las Vegas . ... percentage of growth in each of the following categories: net ... and number of attendees. The 2015 ACMG Annual Meeting was ...
(Date:6/22/2016)... ANGELES , June 22, 2016 /PRNewswire/ ... identity management and verification solutions, has partnered ... edge software solutions for Visitor Management, Self-Service ... provides products that add functional enhancements ... partnership provides corporations and venues with an ...
Breaking Biology News(10 mins):
(Date:6/27/2016)...  Alex,s Lemonade Stand Foundation (ALSF), a leading national ... a state-of-the-art bioinformatics lab, using ,big data, to advance ... as Liz Scott , co-executive director of ALSF ... in Washington, D.C. , hosted by ... advocate of pediatric cancer research and awareness. ...
(Date:6/27/2016)... , June 27, 2016  Global demand for ... percent through 2020 to $7.2 billion.  This market ... beverages, cleaning products, biofuel production, animal feed, and ... diagnostics, and biocatalysts). Food and beverages will remain ... by increasing consumption of products containing enzymes in ...
(Date:6/27/2016)... /PRNewswire/ - BIOREM Inc. (TSX-V: BRM) ("Biorem" or "the Company") ... shareholders, Clean Technology Fund I, LP and Clean Technology ... based venture capital funds which together hold approximately 59% ... diluted, as converted basis), that they have entered into ... holdings in Biorem to TUS Holdings Co. Ltd. ("TUS") ...
(Date:6/27/2016)... DIEGO , June 27, 2016  Sequenom, Inc. ... committed to enabling healthier lives through the development of ... Court of the United States ... courts that the claims of Sequenom,s U.S. Patent No. ... patent eligibility criteria established by the Supreme Court,s Mayo ...
Breaking Biology Technology: