Copper chaperone for superoxide dismutase co-aggregates with superoxide dismutase 1 (SOD1) in neuronal Lewy body-like hyaline inclusions: an immunohistochemical study on familial amyotrophic lateral sclerosis with SOD1 gene mutation
Copper chaperone for superoxide dismutase co-aggregates with superoxide dismutase 1 (SOD1) in neuronal Lewy body-like hyaline inclusions: an immunohistochemical study on familial amyotrophic lateral sclerosis with SOD1 gene mutation
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DOI：
10.1007/s004010000355
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发表时间：
2001-09
影响因子：
12.7
通讯作者：
S. Kato;H. Sumi‐Akamaru;H. Fujimura;S. Sakoda;Masako Kato;A. Hirano;M. Takikawa;E. Ohama
中科院分区：
文献类型：
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作者：
S. Kato;H. Sumi‐Akamaru;H. Fujimura;S. Sakoda;Masako Kato;A. Hirano;M. Takikawa;E. Ohama
超氧化物歧化酶的铜分子伴侣（CCS）与Cu/Zn结合的超氧化物歧化酶1（SOD 1）特异性相互作用，并将铜传递给SOD 1。为了确定CCS-SOD 1相互作用在SOD 1突变的家族性肌萎缩侧索硬化症（FALS）患者发病机制中的作用，我们制备了一种针对CCS的亲和纯化兔抗体，并研究了两名患有两种类型脊髓损伤的FALS患者脊髓中神经元路易体样透明包涵体（LBHI）中CCS和SOD 1的免疫组织化学定位。SOD 1基因第126位密码子碱基对缺失和3例第4位密码子Ala被瓦尔取代的患者。前角细胞中的LBHI从5例FALS患者表现出相同的免疫反应CCS：反应产物存款与抗CCS的抗体一般限于周边的核心和晕型LBHI。CCS和SOD 1的免疫反应性在包涵体中的定位是相似的：在5名突变型SOD 1连锁的FALS患者中，CCS和SOD 1共定位于神经元LBHI中。我们的研究结果表明，特异性的相互作用和聚集的CCS-SOD 1（可能是CCS突变的SOD 1）在SOD 1突变的患者可能会放大夹杂物的形成，并强调更显着的突变SOD 1介导的毒性。
The copper chaperone for superoxide dismutase (CCS) interacts with Cu/Zn-binding superoxide dismutase 1 (SOD1) specifically and delivers copper to SOD1. To determine the role of the CCS-SOD1 interaction in the pathogenesis of SOD1-mutated familial amyotrophic lateral sclerosis (FALS) patients, we produced an affinity-purified rabbit antibody against CCS and investigated the immunohistochemical localization of both CCS and SOD1 in neuronal Lewy body-like hyaline inclusions (LBHIs) in the spinal cords of two FALS patients with a two-base pair deletion at codon 126 in the SOD1 gene and three FALS patients with an Ala to Val substitution at codon 4. The LBHIs in anterior horn cells from the five FALS patients showed identical immunoreactivities for CCS: the reaction product deposits with the antibody against CCS were generally restricted to the periphery of the core and halo-type LBHIs. The localizations of the immunoreactivities for CCS and SOD1 were similar in the inclusions: both CCS and SOD1 colocalized in neuronal LBHIs in the five mutant SOD1-linked FALS patients. Our results suggest that the specific interaction and aggregation of CCS-SOD1 (probably CCS-mutant SOD1) in SOD1-mutated FALS patients may amplify the formation of inclusions and emphasize a more marked mutant SOD1-mediated toxicity.