Cardozo-Pelaez F, Song S, Parthasarathy A, Epstein C J, Sanchez-Ramos J
Department of Neurology, University of South Florida, Tampa 33612, USA.
Neurobiol Aging. 1998 Jul-Aug;19(4):311-6. doi: 10.1016/s0197-4580(98)00067-0.
Age-dependent accumulation of oxidative DNA and protein damage in brainstem and striatum was assessed in normal and transgenic (tg) mice which overexpress human Cu/Zn superoxide dismutase (h-SOD1). A marker of oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine (oxo8dG), was measured at 3, 12, and 18 months of age in control and tg mice. Cu/Zn SOD, but not MnSOD, activities in brainstems and striata from tg mice were increased compared to controls at all ages. At 18 months, oxo8dG levels were increased by 58% in brainstem and by 21% in striatum of control mice. In the tg mice, brainstem and striatal oxo8dG levels were increased to a lesser extent than in the corresponding controls. Protein oxidation (carbonyl content), was increased by 59% at 18 months in control brainstem, but not in striatum, and the increase was significantly attenuated in the tg mice. In summary, oxidative damage to DNA and protein increased with age in brainstem (and to a lesser extent in striatum), and augmented Cu/Zn SOD activity modified the extent of DNA and protein damage.
在正常小鼠和过表达人铜/锌超氧化物歧化酶（h-SOD1）的转基因（tg）小鼠中，评估了脑干和纹状体中与年龄相关的氧化性DNA和蛋白质损伤的积累情况。在3、12和18月龄的对照小鼠和tg小鼠中，测量了氧化性DNA损伤的标志物8-羟基-2'-脱氧鸟苷（oxo8dG）。与对照组相比，tg小鼠脑干和纹状体中铜/锌超氧化物歧化酶（Cu/Zn SOD）的活性在所有年龄段均升高，而锰超氧化物歧化酶（MnSOD）的活性无变化。18月龄时，对照小鼠脑干中oxo8dG水平升高了58%，纹状体中升高了21%。在tg小鼠中，脑干和纹状体中oxo8dG水平的升高幅度小于相应的对照组。蛋白质氧化（羰基含量）在18月龄时，对照小鼠脑干中升高了59%，纹状体中未升高，而在tg小鼠中这种升高明显减弱。总之，脑干中DNA和蛋白质的氧化性损伤随年龄增加（纹状体中程度较轻），Cu/Zn SOD活性增强改变了DNA和蛋白质损伤的程度。
