title: The three isoforms of hepcidin in human serum and their processing determined by liquid chromatography-tandem mass spectrometry (LC-tandem MS).
abstract: Hepcidin, the iron regulatory hormone, has three isoforms; -20, -22 and -25. While hepcidin-25 has been studied extensively, the physiological significance of other isoforms remains poorly understood. Using a quantitative method based on liquid chromatography-tandem mass spectrometry (LC-tandem MS) developed by our group, we quantified hepcidin isoforms in human serum to elucidate their characteristics, and investigated the role of hepatocytes in isoform processing. Hepcidin isoforms in serum obtained from 40 healthy volunteers were quantified. Synthetic hepcidin peptides were added to healthy serum, and to HepG2 culture media, and hepcidin isoform concentrations determined. All three hepcidin isoforms were detected in human serum; however, hepcidin-25 concentrations were highest. The three hepcidin isoforms showed a strong positive correlation with each other and with serum ferritin. Additionally, while hepcidin-20 was strongly correlated with serum creatinine, the other isoforms were not. Hepcidin-20 and -25 levels were also increased in chronic kidney disease (CKD) serum. Hepcidin-22 rapidly degraded into hepcidin-20, whereas hepcidin-25 remained relatively stable. Finally, hepcidin-22 degradation into hepcidin-20 was accelerated in the presence of HepG2. This method has enabled us to reveal fundamental characteristics of the three hepcidin isoforms in serum and may be a powerful tool for quantifying hepcidin isoform expression and processing.
authors.forename: Lynda
authors.initials: L
authors.lastname: Addo
authors.forename: Katsuya
authors.initials: K
authors.lastname: Ikuta
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Yasumichi
authors.initials: Y
authors.lastname: Toki
authors.forename: Mayumi
authors.initials: M
authors.lastname: Hatayama
authors.forename: Masayo
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ito
authors.forename: Motohiro
authors.initials: M
authors.lastname: Shindo
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Shimonaka
authors.forename: Mikihiro
authors.initials: M
authors.lastname: Fujiya
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kohgo
mesh_terms: D018798:Anemia, Iron-Deficiency; D002853:Chromatography, Liquid; D064451:Hepcidins / Q000097:blood*; D006801:Humans; D019190:Iron Overload; D020033:Protein Isoforms / Q000097:blood; D053719:Tandem Mass Spectrometry
chemical_list: D064451:Hepcidins; D020033:Protein Isoforms