[Hepcidin--the discovery of a small protein with a pivotal role in iron homeostasis].
Hepcidin is a small protein comprised of 25 amino acids, synthesized in the liver. It was first described in 2001 as a component of the innate immunity due to its antimicrobial activity. Soon after, hepcidin was recognized as a key component in iron homeostasis, involved in maladies of iron overload or iron deficiency. Hepcidin acts by binding to the transmembrane protein ferroportin, in charge of exporting iron from cells. Upon binding to ferroportin, the latter is internalized into cytoplasmic lysosomes and is hydrolyzed, thus iron is accumulating in cells, and hypoferremia ensues. In hereditary and juvenile types of hemochromatosis, iron overload could be partially due to the down-regulation of hepcidin by the mutated genes HFE and HJV. In ferroportin disease, hepcidin synthesis is not inhibited, yet cells are still overloaded with iron due to mutations in ferroportin, preventing the binding of hepcidin and iron export from cell to the blood. Hepcidin has also been implicated in the scenario related to as "anemia of inflammation". In this condition significant hypoferremia develops as a result of acute sepsis, but also in wake of infections, chronic inflammation, rheumatic diseases and in certain malignancies. Such scarcity of iron leads to anemia that may not be corrected by erythropoietin treatment, and hepcidin synthesis in such anemic state is dramatically elevated. Future therapeutic approach may attempt administering synthetic hepcidin, or its antagonists, to correct states of iron overload or scarcity.
Sela
Ben-Ami
BA
Institute of Chemical Pathology, Sheba Medical Center, Tel Hashomer, Israel. benamis@sheba.health.gov.il
D023181:Antimicrobial Cationic Peptides / Q000502:physiology* / Q000627:therapeutic use; D006432:Hemochromatosis / Q000235:genetics / Q000378:metabolism; D064451:Hepcidins; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000209:etiology / Q000517:prevention & control
D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; D064451:Hepcidins; D007501:Iron