title: Hepcidin-2 in mouse urine as a candidate radiation-responsive molecule.
abstract: We used high-performance liquid chromatography to separate urine obtained from whole-body gamma-irradiated mice (4 Gy) before analyzing each fraction with matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry to identify radiation-responsive molecules. We identified two candidates: hepcidin antimicrobial peptide 2 (hepcidin-2) and peptide fragments of kidney androgen-regulated protein (KAP). We observed that peak increases of hepcidin-2 in urine were delayed in a dose-dependent manner (1 Gy and above); however, the amount of KAP peptide fragments showed no correlation with radiation dose. In addition, an increase in hepcidin-2 after exposure to relatively low radiation doses (0.25 and 0.5 Gy, respectively) was biphasic (at 8-48 h and 120-168 h, respectively, after irradiation). The increase in hepcidin-2 paralleled an increase in hepcidin-2 gene (Hamp2) mRNA levels in the liver. These results suggest that radiation exposure directly or indirectly induces urinary excretion of hepcidin-2 at least in part by the upregulation of Hamp2 mRNA in the liver.
authors.affiliation: Department of Experimental Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8553, Japan Department of Molecular Radiobiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, Japan daisukei@hiroshima-u.ac.jp.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Iizuka
authors.affiliation: Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Higashi-Hiroshima 739-8511, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Yoshioka
authors.affiliation: Department of Molecular Radiobiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Kawai
authors.affiliation: Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Higashi-Hiroshima 739-8511, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Okazaki
authors.affiliation: Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Higashi-Hiroshima 739-8511, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Kiriyama
authors.affiliation: Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Higashi-Hiroshima 739-8511, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Izumi
authors.affiliation: Radiobiology for Children's Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Nishimura
authors.affiliation: Radiobiology for Children's Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Shimada
authors.affiliation: Department of Experimental Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kamiya
authors.affiliation: Department of International Radiation Emergency Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000652:urine; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D064451:Hepcidins / Q000235:genetics / Q000652:urine*; D008099:Liver / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry; D014916:Whole-Body Irradiation
chemical_list: D015415:Biomarkers; C474320:Hamp2 protein, mouse; D064451:Hepcidins; D012333:RNA, Messenger
keywords: hepcidin-2; mass spectrometry; radiation-responsive molecules; urine
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