Hepcidin-2 in mouse urine as a candidate radiation-responsive molecule.
Hepcidin-2 in mouse urine as a candidate radiation-responsive molecule.
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DOI：
10.1093/jrr/rrv098
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发表时间：
2016-03
影响因子：
2
通讯作者：
Suzuki F
中科院分区：
文献类型：
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作者：
Iizuka D;Yoshioka S;Kawai H;Okazaki E;Kiriyama K;Izumi S;Nishimura M;Shimada Y;Kamiya K;Suzuki F
我们使用高效液相色谱法分离从全身γ射线照射小鼠（4戈伊）获得的尿液，然后用基质辅助激光解吸/电离飞行时间质谱法分析每个部分，以识别辐射响应分子。我们确定了两个候选人：hepcidin抗菌肽2（hepcidin-2）和肾雄激素调节蛋白（KAP）的肽片段。我们观察到尿中hepcidin-2的峰值增加以剂量依赖性方式延迟（1戈伊及以上）;然而，KAP肽片段的量显示与辐射剂量无关。此外，在暴露于相对低的辐射剂量（分别为0.25和0.5戈伊）后，铁调素-2的增加是双相的（分别在辐射后8-48小时和120-168小时）。铁调素-2的增加导致肝中铁调素-2基因（Hamp 2）mRNA水平的增加。这些结果表明，辐射暴露直接或间接诱导尿排泄的hepcidin-2至少部分通过上调Hamp 2 mRNA在肝脏中。
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.