Featured Research

from universities, journals, and other organizations

Novel Cause Of Iron Overload In Thalassemia Disorders Discovered

Date:
August 31, 2007
Source:
NIH/National Institute of Diabetes and Digestive and Kidney Diseases
Summary:
Researchers have discovered a novel cause of iron overload in patients with thalassemia. According to the study, thalassemia patients overproduce a protein called GDF15, which suppresses the production of a liver protein, hepcidin, which in turn leads to an increase in the uptake of dietary iron in the gut. This finding has implications for iron metabolism in other diseases and may contribute to the future development of therapies for thalassemia.

Researchers at the National Institutes of Health (NIH) have discovered a novel cause of iron overload in patients with thalassemia, a genetic blood disorder that causes anemia.

According to the study, thalassemia patients overproduce a protein called GDF15, which suppresses the production of a liver protein, hepcidin, which in turn leads to an increase in the uptake of dietary iron in the gut. This finding has implications for iron metabolism in other diseases, including cancer, and may contribute to the future development of therapies for thalassemia.

Thalassemia is an inherited blood disease characterized by the under production of normal hemoglobin, the oxygen-carrying protein in red blood cells. People with severe forms of thalassemia often suffer from anemia, a condition in which the body tissues do not get enough oxygen from the blood, and often require blood transfusions.

Blood transfusions contribute to iron overload in people with thalassemia, but these people also suffer from iron overload independent of blood transfusions. Excess iron causes damage to many organs including the heart and liver, and diabetes can develop in severe cases. Patients with thalassemia often require treatment to remove the excess iron to prevent tissue damage.

"The treatment of iron overload in patients with thalassemia is particularly difficult because of their anemia," says Jeffery L. Miller, M.D., chief of the Molecular Genomics and Therapeutics Section of the Molecular Medicine Branch, Division of Intramural Research, NIDDK, and last author of the study. "So we have been searching for the mechanism responsible for iron overload in thalassemia in hopes of finding new therapies for those patients."

Thalassemia patients absorb too much iron from food due to abnormally low levels of a small peptide, called hepcidin, which regulates iron uptake from the gut. People with thalassemia should produce hepcidin at high levels. Instead, these patients have reduced levels of hepcidin. This confounded the authors and led them to ask if the low levels of hepcidin were somehow caused by the underlying problem in thalassemia -abnormal development of red blood cells.

Red blood cells, also called erythrocytes, are filled with hemoglobin, which transports oxygen throughout the body. Erythrocytes circulate in the blood, but they originate in the bone marrow as erythroblasts and go through several stages of differentiation until they finally leave the bone marrow and enter the blood stream as fully-formed erythrocytes.

Previous research has shown that people with thalassemia disorders have elevated numbers of erythroblasts in the bone marrow, but have reduced numbers of healthy erythrocytes circulating in the blood. Due to the problems with forming hemoglobin, many erythroblasts never make it into the blood stream as healthy erythrocytes.

"Since erythroblasts need iron to make hemoglobin, we reasoned that the increased number of erythroblasts in thalassemia may send stronger messages to the liver to suppress hepcidin and thereby absorb more iron even in the condition of iron overload,” says the study's lead author, Toshihiko Tanno, Ph.D., an investigator in Miller's laboratory in the NIDDK's Division of Intramural Research.

With this hypothesis in mind, Dr. Tanno set out to identify all the messages that are produced by adult stem cells, as they become erythroblasts and red blood cells. For this work, the team was able to examine all the genes expressed in those cells because a catalogue of those genes now exists based upon the NIH's Human Genome Project. The authors identified growth differentiation factor 15 (GDF15) protein as being unusually elevated in people with thalassemia compared to healthy volunteers. Further study showed that GDF15 does indeed signal reduced hepcidin production in liver cells, and the study revealed additional erythroblast proteins that may be involved.

"We are continuing the search for other factors that regulate expression of hepcidin," says Miller. "We are also keenly interested in determining if the elevated levels of GDF15 cause other problems in thalassemia in addition to hepcidin suppression."

The team is now developing strategies to apply and translate their discovery into new diagnostic and therapeutic tools for the clinic. Drs. Miller and Tanno both agreed that while their discovery is a good start, the project will not be complete until the patients have benefited.

The study, led by researchers at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at the NIH, appears online August 26, 2007, as an Advanced Online Publication in the journal, Nature Medicine.


Story Source:

The above story is based on materials provided by NIH/National Institute of Diabetes and Digestive and Kidney Diseases. Note: Materials may be edited for content and length.


Cite This Page:

NIH/National Institute of Diabetes and Digestive and Kidney Diseases. "Novel Cause Of Iron Overload In Thalassemia Disorders Discovered." ScienceDaily. ScienceDaily, 31 August 2007. <www.sciencedaily.com/releases/2007/08/070830122255.htm>.
NIH/National Institute of Diabetes and Digestive and Kidney Diseases. (2007, August 31). Novel Cause Of Iron Overload In Thalassemia Disorders Discovered. ScienceDaily. Retrieved October 21, 2014 from www.sciencedaily.com/releases/2007/08/070830122255.htm
NIH/National Institute of Diabetes and Digestive and Kidney Diseases. "Novel Cause Of Iron Overload In Thalassemia Disorders Discovered." ScienceDaily. www.sciencedaily.com/releases/2007/08/070830122255.htm (accessed October 21, 2014).

Share This



More Health & Medicine News

Tuesday, October 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

CDC Revamps Ebola Guidelines After Criticism

CDC Revamps Ebola Guidelines After Criticism

Newsy (Oct. 21, 2014) The Centers for Disease Control and Prevention have issued new protocols for healthcare workers interacting with Ebola patients. Video provided by Newsy
Powered by NewsLook.com
WHO: Ebola Vaccine Trials to Start a in January

WHO: Ebola Vaccine Trials to Start a in January

AP (Oct. 21, 2014) Tens of thousands of doses of experimental Ebola vaccines could be available for "real-world" testing in West Africa as soon as January as long as they are deemed safe in soon to start trials, the World Health Organization said Tuesday. (Oct. 21) Video provided by AP
Powered by NewsLook.com
First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

Newsy (Oct. 21, 2014) A medical team has for the first time given a man the ability to walk again after transplanting cells from his brain onto his severed spinal cord. Video provided by Newsy
Powered by NewsLook.com
CDC Issues New Ebola Guidelines for Health Workers

CDC Issues New Ebola Guidelines for Health Workers

Reuters - US Online Video (Oct. 21, 2014) The U.S. Centers for Disease Control and Prevention has set up new guidelines for health workers taking care of patients infected with Ebola. Linda So reports. Video provided by Reuters
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins