Increased oxidative damage to DNA in a transgenic mouse model of Huntington's disease
Increased oxidative damage to DNA in a transgenic mouse model of Huntington's disease
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DOI：
10.1046/j.1471-4159.2001.00689.x
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发表时间：
2001-12-01
影响因子：
4.7
通讯作者：
Beal, MF
中科院分区：
文献类型：
--
作者：
Bogdanov, MB;Andreassen, OA;Beal, MF
线粒体功能障碍和氧化损伤可能在亨廷顿病（HD）的发病机制中发挥作用。我们在 HD 转基因小鼠模型 (R6/2) 中检测了 8-羟基-2-脱氧鸟苷 (OH(8)dG) 的浓度，这是一种公认的 DNA 氧化损伤标记物。 HD 小鼠的尿液、血浆和纹状体微透析液中发现 OH(8)dG 浓度增加。在 12 周和 14 周龄时，分离的脑 DNA 中也观察到浓度增加。免疫细胞化学显示疾病晚期 OH(8)dG 染色增加。这些结果表明，氧化损伤可能在 HD 的 R6/2 转基因小鼠模型神经元变性的发病机制中发挥作用。
Mitochondrial dysfunction and oxidative damage may play a role in the pathogenesis of Huntington's disease (HD). We examined concentrations of 8-hydroxy-2-deoxyguanosine (OH(8)dG), a well-established marker of oxidative damage to DNA, in a transgenic mouse model of HD (R6/2). Increased concentrations of OH(8)dG were found in the urine, plasma and striatal microdialysates of the HD mice. Increased concentrations were also observed in isolated brain DNA at 12 and 14 weeks of age. Immunocytochemistry showed increased OH(8)dG staining in late stages of the illness. These results suggest that oxidative damage may play a role in the pathogenesis of neuronal degeneration in the R6/2 transgenic mouse model of HD.