Detection of serum hepcidin in renal failure and inflammation by using ProteinChip System
Detection of serum hepcidin in renal failure and inflammation by using ProteinChip System
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DOI：
10.1182/blood-2005-10-4043
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发表时间：
2006-08-15
期刊：
影响因子：
20.3
通讯作者：
Ishikawa, Isao
中科院分区：
文献类型：
--
作者：
Tomosugi, Naohisa;Kawabata, Hiroshi;Ishikawa, Isao
Hepcidin是铁代谢的关键调节因子，在肝脏中表达，在血液中分布，在尿液中排泄。然而，到目前为止，还没有可靠和实用的方法来测量血清中hepcidin的bloactive形式。在这里，我们使用表面增强激光解吸电离飞行时间质谱（SELDI-TOF MS）来分析血液透析患者独特的血清蛋白质组学模式。在1000 ~ 15000 m/z范围内，我们发现2192、2789和2851 m/z的肽与血清铁蛋白水平显著相关。在2192和2789 m/z处的多肽分子大小分别与报道的hepcidin-20和-25的大小相匹配，并且在2789 m/z处的血清多肽通过碰撞诱导解离串联质谱鉴定为hepcidin-25。在这个实验中，血清hepcidin-25的水平与血清铁蛋白和血清白介素-6的水平有很好的相关性。血液透析患者血清中发现Hepcidin-25蓄积；这可能有助于肾性贫血的发病机制，通过减少可用于造血的铁。因此，SELDI-TOF质谱将成为检测和半定量血清中hepcidin生物活性的临床有用工具。
Hepcidin, a key regulator of iron metabolism, is expressed in the liver, distributed in blood, and excreted in urine. However, to date, no reliable and practical method for measuring the bloactive form of hepcidin in serum has been developed. Here, we used surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF MS) to analyze the distinctive serum proteomic patterns of patients receiving hemodialysis. In the range of 1000 to 15 000 m/z, we found peptides at 2192, 2789, and 2851 m/z that showed a significant correlation with the serum ferritin levels. The molecular sizes of peptides at 2192 and 2789 m/z matched with the reported sizes of hepcidin-20 and -25, respectively, and the serum peptide at 2789 m/z was identified as hepcidin-25 by collision-induced dissociation tandem MS. By using SELDI-TOF MS, we developed a serniquantitative assay for hepcidin-25. In this assay, the level of serum hepcidin-25 correlated well with levels of serum ferritin and serum interleukin-6. Hepcidin-25 was found to accumulate in the serum of patients receiving hemodialysis; this could contribute to the pathogenesis of renal anemia by decreasing the available iron for hematopoiesis. Thus, SELDI-TOF MS would be a clinically useful tool to detect and semiquantify bioactive hepcidin in serum.