The three isoforms of hepcidin in human serum and their processing determined by liquid chromatography-tandem mass spectrometry (LC-tandem MS)
Autor: | Yasushi Shimonaka, Yasumichi Toki, Yutaka Kohgo, Motohiro Shindo, Katsuya Ikuta, Satoshi Ito, Yusuke Sasaki, Masayo Yamamoto, Hiroki Tanaka, Lynda Addo, Mayumi Hatayama, Mikihiro Fujiya |
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Rok vydání: | 2015 |
Předmět: |
inorganic chemicals
0301 basic medicine Gene isoform congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty Iron Overload LC Hepcidin Tandem mass spectrometry digestive system 03 medical and health sciences chemistry.chemical_compound Hepcidins Liquid chromatography–mass spectrometry Tandem Mass Spectrometry hemic and lymphatic diseases Internal medicine medicine Humans Protein Isoforms Tandem MS Creatinine Hematology biology Anemia Iron-Deficiency Chemistry Hepcidin isoforms nutritional and metabolic diseases Iron deficiency medicine.disease 030104 developmental biology Endocrinology Biochemistry biology.protein Hormone Chromatography Liquid |
Zdroj: | International journal of hematology. 103(1) |
ISSN: | 1865-3774 |
Popis: | The final publication is available at Springer via http://dx.doi.org/10.1007/s12185-015-1885-y 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. |
Databáze: | OpenAIRE |
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