Hepcidins in amphibians and fishes: Antimicrobial peptides or iron-regulatory hormones?
Hepcidin, originally identified as a 25 amino acid peptide antibiotic produced in the liver, is a key regulator of iron balance and recycling in humans and mice. Closely related hepcidin genes and peptides also have been identified in other mammals, amphibians, and a number of fish species. We hypothesize that hepcidin, the iron-regulatory hormone in humans, may have evolved from an antimicrobial peptide in fishes. In this review we will highlight the evidence that indicates hepcidin evolved from an antimicrobial peptide to an iron-regulatory hormone in vertebrate evolution. This evidence includes the discovery of hepcidin as an antimicrobial peptide and iron-regulatory hormone, structural comparison of mammalian hepcidins and nonmammalian hepcidins, and the cellular and molecular evidence indicating that, while some fish hepcidins may serve only as antimicrobial peptides, other fish and amphibian hepcidins may function as iron regulators.
Shi
Jishu
J
Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, 212 Greene Hall, Auburn, AL 36849, USA. shijish@vetmed.auburn.edu
Camus
Alvin C
AC
D000595:Amino Acid Sequence; D000663:Amphibians / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D019143:Evolution, Molecular; D005399:Fishes / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D064451:Hepcidins; D035925:Iron-Regulatory Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D008969:Molecular Sequence Data; D016415:Sequence Alignment
D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; C579599:Hamp protein, mouse; D064451:Hepcidins; D035925:Iron-Regulatory Proteins