Discovery Could Lead To New Treatments For Chronic Illnesses Related To Abnormal Iron Metabolism

Ferritin is a protein that stores or releases iron in the body as it isneeded. Until now, scientists were convinced that the only way todevelop new therapies for treating iron overload was to focus on ironmetabolism. But a new study published in the October 10th issue of theProceedings of the National Academy of Sciences is the first todemonstrate that the ferritin gene can be controlled by heme, and othercommon antioxidant regulators. Heme is the molecule that activates manyprotective genes and is also the part of the blood that uses iron tocarry oxygen from our lungs to the rest of the body.

Previously, scientists only focused on genes that were regulated byiron for iron related diseases. Now it is clear that heme might be a"master switch" for iron genes, and antioxidant genes, which are thegenes that protect and repair damage caused by oxygen radicals. If thatmechanism is found, heme could help scientists unravel the cause andcures of several chronic illnesses.

"This new information will dramatically change the way researchersthink about solving certain health problems involving iron orinflammation," said Elizabeth Theil, Ph.D., Senior Scientist atChildren's Hospital Oakland Research Institute and co-author of thestudy. "For the first time we understand that ferritin is one of theprotective genes the body uses to protect us from the damage caused byoxygen radicals. "

To find out what controlled ferritin genes; scientists studied culturesof liver cells. They found that iron, by itself, was a weak signal bylinking different pieces of ferritin DNA to a "reporter" gene andmeasuring the amount of reporter protein when cells were fed extrairon, heme, or sulforphane. Iron had practically no effect, but withheme or sulforphane much "reporter" was produced.

Scientists discovered that ferritin is a gene with two kinds of geneticcontrollers: DNA plus mRNA. Iron regulates the mRNA. When the tworegulators were combined in the experiment, heme made the cells producehuge amounts of reporter protein - three times more than either onealone. Both DNA and mRNA carry genetic information. DNA is theblueprint, protected in the nucleus, and mRNA is the working copiesused to manage day-to-day information and cell work.

"Our research shows that ferritin mRNA is sensitive to iron, ferritinDNA is sensitive to antioxidants like sulforphane and heme coordinatesboth DNA and mRNA," said Korry Hintze, a postdoctoral fellow atChildren's Hospital Oakland Research Institute and co-author of thestudy. "Now we know that ferritin is central to both iron and oxygenmetabolism."

About Children's Hospital & Research Center at Oakland
Children's Hospital & Research Center at Oakland is a designatedLevel I pediatric trauma center and the largest pediatric critical carefacility in the region. The hospital has 170 licensed beds and 166hospital-based physicians in 30 specialties, two thousand employees,and an operating budget of $200 million. With more than 300 basic andclinic investigators and an annual budget of over $43 million, theresearch institute has made significant progress in areas includingpediatric obesity, cancers, sickle cell disease, AIDS/HIV, hemophiliaand cystic fibrosis.