Hepcidin/LEAP-1 (Human)

Novel Antimicrobial Peptides identified in Human Blood Ultrafiltrate

Antimicrobial peptides from plants and animals are classified into several groups or classes; these include the disulfide cross-linked peptides known as defensins[Nature, 475, 389 (2002)]. LEAP-1 , a 25 amino acid residue peptide with antimicrobial activity containing 4 intramolecular disulfide linkages was recently identified in human blood ultrafiltrate. This new peptide has now been included as a member of the disulfide cross-linked class of antimicrobial peptides[FEBS Lett., 480, 147 (2000)]. The same peptide named hepcidin (Hepc) with 25 amino acid residues (Hepc25) together with the amino-terminally truncated peptides (Hepc22 and Hepc20) were isolated from human urine by another group[J. Biol. Chem., 276, 7806 (2001)]. The disulfide arrangement of this peptide has very recently been reported[J. Biol. Chem., 277, 37597 (2002)].




LEAP-1 was named after its characteristic feature as a"liver-expressed antimicrobial peptide ". Actually, this peptide exerts its antimicrobial effect against both Gram-positive and Gram-negative bacteria as well as yeast; for example, the IC50 value against Saccharomyces cerevisiae was 18 mM[FEBS Lett., 480, 147 (2000)]. This activity is salt-sensitive[J. Biol. Chem., 276, 7806 (2001)]. Gene expression of LEAP-1 was detected in extremely high levels in the liver, and to a significant but lesser extent in the heart and brain. No gene expression was observed in the kidney. Subsequently, supporting data has been accumulated showing that this peptide is involved in the regulation of iron homeostasis[Proc. Natl. Acad. Sci. U.S.A., 98, 8160 (2001)].

This multifunctional peptide, LEAP-1/hepcidin, should be a useful tool in the clarification of the liver's biological functions.