UCLA and Univ. of Utah researchers identify how a hormone regulates iron
Findings may lead to treatments for hemochromatosis and anemia of chronic disease
A new UCLA and University of Utah study found how a hormone called hepcidin regulates the iron uptake from the diet and its distribution in the body. The study may help develop future treatments for chronic anemia and for diseases of iron overload, such as hemochromatosis. Published online in the journal Science this week, researchers discovered that the hormone hepcidin controls ferroportin, an iron-transporting molecule on the surface of specific cells that contain iron. Hepcidin signals ferroportin not to release iron into the blood stream.
Researchers realized that if there isn’t enough hepcidin to regulate ferroportin, too much iron is taken up from the digestive system into the body, which can lead to hemochromatosis, a major genetic disorder affecting about a million people in the United States. "For the first time we understand what happens in the disease hemochromatosis," said Dr. Tomas Ganz, Ph.D., M.D., one of the study’s principal investigators and professor of medicine and pathology at the David Geffen School of Medicine at UCLA. "We knew that ferroportin is necessary to help release iron into the bloodstream, but didn’t know that hepcidin directly regulates this activity."
Ganz adds that too much hepcidin present in the body -- which can occur in patients with infections or with inflammatory diseases such as rheumatoid arthritis or inflammatory bowel disease -- often results in not enough iron released into the blood stream causing chronic anemia. "We have defined how the hormone hepcidin regulates the accumulation of iron by the body," says Jerry Kaplan, Ph.D., one of the study’s principal authors and a professor of pathology and assistant vice president for basic science at the University of Utah Health Sciences Center. "This has implications for understanding both diseases that are caused by not enough iron and diseases that are caused by too much iron."
In a cell culture, researchers added hepcidin to cells and found that hepcidin attaches to ferroportin and causes ferroportin to be swallowed and destroyed by the cells. Without ferroportin on the surface to release the iron, the mineral remains trapped inside the cell. "Our findings may lead to new interventions for specific diseases," said Dr. Elizabeta Nemeth, the study’s first author and assistant research professor, Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA. "Our next step will be to look more closely at molecular interactions of hepcidin and ferroportin in order to be able to develop treatment drugs."
Nemeth says that a form of hepcidin may be developed that people with hemochromatosis could inject to help reduce the amount of iron taken up by the body – similar to the use of insulin to control the amount of sugar in the body. For patients with anemia associated with too much hepcidin, Ganz adds that development of drugs to block hepcidin from binding to ferroportin might help release more iron into the body.
Hemochromatosis is the most common genetic disease in the United States according to the Centers for Disease Control. One in 100-200 people have a double mutation of a gene that puts them at risk for developing hemochromatosis, which causes an accumulation of excess iron in body tissues. Anemia of chronic disease is second only to iron-deficiency as a cause of anemia worldwide.
The National Institutes of Health funded the study. Other authors include: Marie S. Tuttle, Julie Powelson, Michael B. Vaughn and Diane McVey Ward from the Department of Pathology, School of Medicine, University of Utah; and Adriana Donovan, Department of Hematology, Children’s Hospital, Boston, MA.
Rachel Champeau | EurekAlert!
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