ITIH4 and Gpx3 are potential biomarkers for amyotrophic lateral sclerosis
ITIH4 and Gpx3 are potential biomarkers for amyotrophic lateral sclerosis
复制标题
DOI：
10.1007/s00415-013-6877-3
复制
发表时间：
2013-02
影响因子：
6
通讯作者：
Hirotaka Tanaka;M. Shimazawa;M. Takata;Hideo Kaneko;K. Tsuruma;T. Ikeda;H. Warita;M. Aoki;
中科院分区：
文献类型：
--
作者：
Hirotaka Tanaka;M. Shimazawa;M. Takata;Hideo Kaneko;K. Tsuruma;T. Ikeda;H. Warita;M. Aoki;
肌萎缩侧索硬化症（ALS）的诊断是困难的，由于缺乏明确的生物标志物。我们的目的是确定特征性血清蛋白模式，可以提供候选生物标志物的ALS。我们根据疾病进展将突变型超氧化物歧化酶-1（SOD 1）H46 R大鼠分为三组：症状前（90天）、发病和终末期。双向电泳分离血清蛋白后，我们选择清晰的蛋白质斑点，并确定了两个候选蛋白质-间-α-胰蛋白酶抑制剂重链H4（ITIH 4）和谷胱甘肽过氧化物酶3（Gpx 3）。在SOD 1H 46 R大鼠血清中，120 kDa ITIH 4在疾病开始时增加，85 kDa ITIH 4在疾病终末期时增加。与对照组或肌营养不良症、阿尔茨海默病或帕金森病患者相比，ALS中85 kDa ITIH 4的表达是显著的。SOD_（1H）_（46）R大鼠血清中Gpx_3蛋白水平在发病前升高，随着病情进展逐渐下降。ALS患者血清中Gpx 3蛋白水平低于其他疾病患者。这些结果表明ITIH 4和Gpx 3是ALS的潜在生物标志物。
The diagnosis of amyotrophic lateral sclerosis (ALS) is difficult due to lack of definitive biomarkers. Our aim was to identify characteristic serum protein patterns that could provide candidate biomarkers for ALS. We divided mutant superoxide dismutase-1 (SOD1)H46Rrats into three groups based on disease progression: pre-symptom (90 days), onset, and end-stage. After separation of serum proteins using two-dimensional electrophoresis, we selected clear protein spots and identified two candidate proteins—inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) and glutathione peroxidase 3 (Gpx3). The 120 kDa ITIH4 increased at the onset of the disease and the 85 kDa ITIH4, a cleaved form, at the end-stage in the sera of the SOD1H46Rrats. Expression of the 85 kDa ITIH4 was substantial in ALS compared with controls or patients with muscular dystrophy, Alzheimer diseases, or Parkinson diseases. The Gpx3 protein levels in the sera of SOD1H46Rrats were upregulated pre-symptom and gradually decreased as the disease progressed. The Gpx3 protein levels were lower in the sera of the patients with ALS than in other diseases. These results indicate that ITIH4 and Gpx3 are potential biomarkers for ALS.