Intense superoxide dismutase-1 immunoreactivity in intracytoplasmic hyaline inclusions of familial amyotrophic lateral sclerosis with posterior column involvement
Intense superoxide dismutase-1 immunoreactivity in intracytoplasmic hyaline inclusions of familial amyotrophic lateral sclerosis with posterior column involvement
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DOI：
10.1097/00005072-199604000-00011
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发表时间：
1996-04-01
影响因子：
3.2
通讯作者：
Asayama, K
中科院分区：
文献类型：
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作者：
Shibata, N;Hirano, A;Asayama, K
本报告涉及三名患有后柱受累的家族性肌萎缩侧索硬化症 (ALS) 患者的前角细胞胞浆内透明包涵体 (IHI) 中超氧化物歧化酶-1 (SOD1) 的回顾性免疫组织化学和免疫电子显微镜研究。所有患者都是美国“C”家族的成员。三位患者的一些受影响神经元的体细胞和索状肿胀神经突中存在的几乎所有 IHI 均被人 SOD1 抗体强烈染色。相比之下，ALS 患者和 10 名对照个体的前角细胞的细胞质仅对抗体产生微弱反应或根本不反应。免疫电子显微镜显示，构成 IHI 的颗粒相关的粗线性结构被 SOD1 抗体强烈标记。 IHI 也被泛素和磷酸化神经丝蛋白抗体呈阳性染色，免疫反应性分布与抗 SOD1 抗体相似。 DNA 分析揭示了患者脑样本及其家庭成员外周血中 SOD1 基因密码子 4（Ala(4) --> Val）处的单位点 GCC 至 GTC 替换。我们的结果表明，SOD1 是 IHI 的一个组成部分，可能与泛素和神经丝蛋白相互作用，并指出 IHI 中强烈 SOD1 免疫反应性的存在可能与涉及突变基因编码的结构改变的 SOD1 分子的过程相关。
This report concerns retrospective immunohistochemical and immunoelectron microscopic studies on superoxide dismutase-l (SOD1) in intracytoplasmic hyaline inclusions (IHIs) of the anterior horn cells of three patients with familial amyotrophic lateral sclerosis (ALS) with posterior column involvement. All of the patients were members of the American ''C'' family. Almost all of the IHIs, present in the soma and cordlike swollen neurites of some affected neurons of the three patients, were intensely stained by an antibody to human SOD1. By contrast, the cytoplasm of anterior horn cells of the ALS patients and of ten control individuals reacted only weakly with the antibody or not at all. Immunoelectron microscopy revealed that the granule-associated thick linear structures that composed the IHIs were intensely labeled by the antibody to SOD1. The IHIs were also positively stained by antibodies to ubiquitin and phosphorylated neurofilament protein, with the distribution of immunoreactivity resembling that seen with the anti-SOD1 antibody. The DNA analysis disclosed a single-site GCC to GTC substitution at codon 4 (Ala(4) --> Val) in the SOD1 gene from the brain samples of the patients and from the peripheral blood of their family members. Our results suggest that SOD1 is a component of IHIs and may interact with ubiquitin and neurofilament protein, and point to the possibility that the presence of intense SOD1 immunoreactivity in the IHIs may be of relevance in processes involving structurally altered SOD1 molecules encoded by the mutated gene.