Shibata N, Nagai R, Miyata S, Jono T, Horiuchi S, Hirano A, Kato S, Sasaki S, Asayama K, Kobayashi M
Department of Pathology, Tokyo Women's Medical University, Japan.
Acta Neuropathol. 2000 Sep;100(3):275-84. doi: 10.1007/s004019900173.
To assess a role for oxidative stress in the pathogenesis of amyotrophic lateral sclerosis (ALS), we analyzed the immunohistochemical localization of 8-hydroxy2'-deoxyguanosine (OHdG) as a nucleic acid oxidation product, acrolein-protein adduct and 4-hydroxy-2-nonenal (HNE)-protein adduct as lipid peroxidation products, Nepsiloncarboxymethyl-lysine (CML) as a lipid peroxidation or protein glycoxidation product, pentosidine as a protein glycoxidation product, and imidazolone and pyrraline as nonoxidative protein glycation products in the spinal cord of three familial ALS patients with superoxide dismutase(SOD 1) A4V mutation, six sporadic ALS patients, and six age-matched control individuals. The spinal cord sections of the control cases did not show any distinct immunoreactivities for these examined products. In the familial ALS cases, intense immunoreactivities for pyrraline and CML were confined to the characteristic Lewy body-like hyaline inclusions, and imidazolone immunoreactivity was located in the cytoplasm of the residual motor neurons. No significant immunoreactivities for other examined products were detected in the familial ALS spinal cords. In the sporadic ALS cases, intense immunoreactivities for pentosidine, CML and HNE-protein adduct were seen in the cytoplasm of the degenerated motor neurons, and OHdG immunoreactivity was located in the cell nuclei of the residual neurons and glial cells. The present results indicate that oxidative reactions are involved in the disease processes of sporadic ALS, while there is no evidence for increased oxidative damage except for CML deposition in the familial ALS spinal cords. Furthermore, it is likely that the accumulation of pyrraline and imidazolone supports a nonoxidative mechanism in SOD1-related motor neuron degeneration.
为了评估氧化应激在肌萎缩侧索硬化症（ALS）发病机制中的作用，我们分析了3例携带超氧化物歧化酶（SOD1）A4V突变的家族性ALS患者、6例散发性ALS患者以及6例年龄匹配的对照个体脊髓中作为核酸氧化产物的8-羟基-2'-脱氧鸟苷（OHdG）、作为脂质过氧化产物的丙烯醛-蛋白质加合物和4-羟基-2-壬烯醛（HNE）-蛋白质加合物、作为脂质过氧化或蛋白质糖氧化产物的Nε-羧甲基赖氨酸（CML）、作为蛋白质糖氧化产物的戊糖苷以及作为非氧化蛋白质糖基化产物的咪唑啉酮和吡咯赖氨酸的免疫组织化学定位。对照病例的脊髓切片对这些检测产物均未显示出任何明显的免疫反应性。在家族性ALS病例中，吡咯赖氨酸和CML的强烈免疫反应性局限于特征性的路易体样透明包涵体，咪唑啉酮免疫反应性位于残留运动神经元的细胞质中。在家族性ALS脊髓中未检测到其他检测产物的明显免疫反应性。在散发性ALS病例中，戊糖苷、CML和HNE-蛋白质加合物的强烈免疫反应性出现在变性运动神经元的细胞质中，OHdG免疫反应性位于残留神经元和胶质细胞的细胞核中。目前的结果表明，氧化反应参与散发性ALS的疾病进程，而除了家族性ALS脊髓中有CML沉积外，没有证据表明氧化损伤增加。此外，吡咯赖氨酸和咪唑啉酮的积累可能支持SOD1相关运动神经元变性的非氧化机制。
