Schwartz P J, Coyle J T
Laboratory of Molecular and Developmental Neuroscience, Massachusetts General Hospital, Charlestown, USA.
Synapse. 1998 Jul;29(3):206-12. doi: 10.1002/(SICI)1098-2396(199807)29:3<206::AID-SYN2>3.0.CO;2-A.
The cytoplasmic copper-zinc superoxide dismutase (Cu, Zn SOD; SOD-1) is an abundant and well-conserved intracellular antioxidant enzyme which has been implicated in a number of oxidative stress mediated phenomena, especially Down Syndrome, in which SOD-1 activity is increased due to triplication of chromosome 21 containing the gene and, in hereditary amyotrophic lateral sclerosis, in which the gene is mutated. Overexpression of SOD-1 could theoretically, therefore, lead to increased vulnerability to oxidative stress in two distinct manners: increasing steady-state hydrogen peroxide levels or increasing toxic side reactions. We used two mouse neuronal culture systems--one in which the murine chromosome containing SOD-1 is triplicated and one in which human SOD-1 is a transgene--to test the effect of overexpression of this enzyme on antioxidant status in general and specifically on glutamate mediated oxidative stress. We found that SOD-1 overexpression increases antioxidant status at the same time it decreases vulnerability to glutamate.
细胞质铜锌超氧化物歧化酶（Cu, Zn SOD；SOD-1）是一种丰富且高度保守的细胞内抗氧化酶，它与许多氧化应激介导的现象有关，特别是唐氏综合征，其中由于包含该基因的21号染色体三体化，SOD-1活性增加；以及遗传性肌萎缩侧索硬化症，其中该基因发生突变。因此，理论上SOD-1的过表达可能以两种不同方式导致对氧化应激的易感性增加：增加稳态过氧化氢水平或增加毒性副反应。我们使用了两种小鼠神经元培养系统——一种是含有SOD-1的小鼠染色体三体化的系统，另一种是人类SOD-1作为转基因的系统——来测试这种酶的过表达对一般抗氧化状态的影响，特别是对谷氨酸介导的氧化应激的影响。我们发现SOD-1过表达在增加抗氧化状态的同时降低了对谷氨酸的易感性。
