Hepcidin
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| Hepcidin antimicrobial peptide | |
|---|---|
| Symbol(s): | HAMP |
| Locus: | 19q13.1 |
| AA: | 84 (unproc. precur.)/20, 22, 25 (protein) |
| Codes: | EntrezGene 57817, RefSeq NM_021175, UniProt P81172, Mendelian Inheritance in Man (OMIM) 606464 |
Hepcidin is a recently discovered peptide hormone produced by the liver, that appears to be the master regulator of iron homeostasis in humans and other mammals.[1]
In a search for antimicrobial peptides, researchers working in the lab of Tomas Ganz discovered a peptide associated with inflammation, and named it "hepcidin" after observing that it was produced in the liver ("hep-") and appeared to have bacteriocidal properties ("-cidin" for "killing")[2]. Another group working independently also isolated this peptide and named it LEAP-1, for Liver-Expressed Antimicrobial Protein. Both groups were focused on the antimicrobial properties of the peptide.[3] HAMP is the gene that encodes for hepcidin.
Soon after this discovery, other researchers discovered that hepcidin production in mice increased in conditions of iron overload as well as in inflammation. Genetically modified mice engineered to overexpress hepcidin died shortly after birth with severe iron deficiency, again suggesting a central and not redundant role in iron regulation. The first evidence that linked hepcidin to the clinical condition known as the anemia of inflammation came from the lab of Nancy Andrews in Boston when researchers looked at tissue from two patients with liver tumors with a severe microcytic anemia that did not respond to iron supplementation. The tumor tissue appeared to be overproducing hepcidin, and contained large quantities of hepcidin mRNA. Removing the tumors surgically cured the anemia.
Taken together, these discoveries suggested that hepcidin regulated the release of iron in the body.
More recent discoveries have shown that hepcidin directly interacts with ferroportin, a protein that transports iron out of cells that store it. This is another confirmation that hepcidin is directly involved in iron homeostasis.
Hepcidin has shown fairly consistent activity against fungi. Hepcidin's antibacterial activity currently seems to be inconsistent.
[edit] External links
- Camaschella C. Understanding iron homeostasis through genetic analysis of hemochromatosis and related disorders. Blood 106(12):3710-3717, 1 December 2005.
[edit] References
- ^ Ganz T. Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation. Blood 2003;102:783-788. PMID 12663437.
- ^ Park CH, Valore EV, Waring AJ, Ganz T.Hepcidin, a Urinary Antimicrobial Peptide Synthesized in the Liver. J. Biol. Chem., Vol. 276, Issue 11, 7806-7810, March 16, 2001
- ^ Krausse A. LEAP-1 a novel highly disulphide-bonded human peptide, exhibits antimicrobial activity *note please insert citation, NCBI is down and has been for several minutes*
