The expression of metallothioneins is diminished in the spinal cords of patients with sporadic ALS
The expression of metallothioneins is diminished in the spinal cords of patients with sporadic ALS
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DOI：
10.1080/17482960801934312
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发表时间：
2008-01-01
影响因子：
--
通讯作者：
Inuzuka, Takashi
中科院分区：
文献类型：
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作者：
Hozumi, Isao;Yamada, Mitsunori;Inuzuka, Takashi
我们用免疫组织化学方法分析了ALS患者(n=12)和对照组(n=12)脊髓中MTS的表达。MT-1/2和MT-3主要表达于神经胶质细胞，ALS患者脊髓中MT-1/2和MT-3免疫反应减弱，尤其是戴呼吸机的患者。ALS组MT-1/2免疫反应性较对照组明显降低。此外，统计学分析显示腰髓灰质星形胶质细胞MT-3的免疫反应与ALS病程呈负相关。正常对照组和ALS组MT-1/2和MT-3免疫反应主要分布于胶质细胞，部分神经元也表达MT-1/2和MT-3免疫反应。有趣的是，MT-3阳性神经元的患者在神经元周围显示了明确的MT-3免疫反应神经胶质反应。已有研究报道家族性肌萎缩侧索硬化症(FALS)模型小鼠(G93A SOD1)与MT-1/2或MT-3基因敲除小鼠杂交后ALS表达加速。从这些发现来看，MT-1/2和MT-3在ALS的进展中都起着重要的作用。MT是一种可以清除自由基的防御性蛋白，因此，对其表达的调控对ALS患者具有很强的治疗潜力。
We analyzed the expression of MTs using immunohistochemistry on the spinal cords of patients with ALS (n = 12) and controls (n = 12). The immunoreactivities of both MT-1/2 and MT-3 stained dominantly in glial cells and were decreased in the spinal cords of patients with ALS, particularly in patients on respirators. The immunoreactivity of MT-1/2 in the ALS groups was significantly reduced compared with controls. In addition, a statistical analysis revealed that the immunoreactivity of MT-3 in astrocytes in the gray matter of the lumbar spinal cord was negatively correlated with the duration of ALS. Both MT-1/2 and MT-3 immunoreactivities were detected mainly in the glias and also detected in some neurons in both control patients and patients with ALS. Interestingly, the patients with MT-3-positive neurons showed definite MT-3-immunoreactive glial reaction around neurons. Previous studies have reported that familial ALS (FALS) model mice (G93A SOD1) crossed with MT-1/2 or MT-3 knock-out mice had accelerated expression of ALS. Judged from these findings, both MT-1/2 and MT-3 play important roles in the progression of ALS. MTs are defensive proteins that can scavenge free radicals; therefore, manipulation of their expression has a strong therapeutic potential for ALS patients.