Cova Emanuela, Cereda Cristina, Galli Alberto, Curti Daniela, Finotti Chiara, Di Poto Cristina, Corato Manuel, Mazzini Giuliano, Ceroni Mauro
Laboratory of Experimental Neurobiology, IRCCS, Foundation C. Mondino Institute of Neurology, via Mondino, 2, 27100 Pavia, Italy.
Neurosci Lett. 2006 May 22;399(3):186-90. doi: 10.1016/j.neulet.2006.01.057. Epub 2006 Feb 21.
Markers of oxidative stress have been found in spinal cord, cortex, cerebrospinal fluid, and plasma of SALS patients. Mitochondrial and calcium metabolism dysfunction were also found in peripheral lymphocytes from SALS patients. In this study, we demonstrate that lymphocytes from SALS patients are more prone to undergo alteration of cell membrane integrity both in basal conditions and following oxidative stress induced by H2O2 treatment. The expression of the antioxidant proteins, Bcl-2, SOD1 and catalase in basal conditions, was significantly lower in lymphocytes from SALS patients than in lymphocytes from age and sex matched controls. Exposure to H2O2 induced a time-dependent decrease of Bcl-2 and SOD1 in control lymphocytes. Conversely, the levels of these proteins remained unchanged in SALS lymphocytes even after 18 h stress. Catalase expression was not significantly modified by oxidative stress. Our results demonstrate that two factors involved in the genesis and/or progression of the familial form of the disease with SOD1 mutation are altered also in the sporadic form of ALS and suggest that the oxidative stress protection pathway is deregulated in lymphocytes from ALS patients.
在散发性肌萎缩侧索硬化症（SALS）患者的脊髓、皮质、脑脊液和血浆中均发现了氧化应激标志物。在SALS患者的外周淋巴细胞中还发现了线粒体和钙代谢功能障碍。在本研究中，我们证明，SALS患者的淋巴细胞在基础条件下以及在过氧化氢（H2O2）处理诱导的氧化应激后，更易于发生细胞膜完整性的改变。在基础条件下，抗氧化蛋白Bcl-2、超氧化物歧化酶1（SOD1）和过氧化氢酶在SALS患者淋巴细胞中的表达显著低于年龄和性别匹配的对照者淋巴细胞中的表达。暴露于H2O2会导致对照淋巴细胞中Bcl-2和SOD1随时间下降。相反，即使在应激18小时后，这些蛋白在SALS淋巴细胞中的水平仍保持不变。氧化应激对过氧化氢酶的表达没有显著影响。我们的结果表明，与SOD1突变的家族性疾病形式的发生和/或进展相关的两个因素在散发性肌萎缩侧索硬化症（ALS）中也发生了改变，并提示ALS患者淋巴细胞中的氧化应激保护途径失调。
