Williams R E, Cookson M R, Fray A E, Manning P M, Menzies F M, Figlewicz D A, Shaw P J
Department of Neurology, The Medical School, University of Newcastle, Newcastle upon Tyne, UK.
Neurosci Lett. 2001 Apr 20;302(2-3):146-50. doi: 10.1016/s0304-3940(01)01686-x.
Free radical damage has been implicated in the pathophysiology of motor neurone disease (MND); mutations have been identified in the gene encoding Cu/Zn superoxide dismutase (SOD1). There is evidence that glial cell dysfunction may contribute to motor neurone injury, but the exact role of glial cells in MND has yet to be established. The aim of this study was to determine whether expression of mutant SOD1 affects the response of glia to oxidative stress. Stable C6 glioma cells expressing mutant SOD1 and cortical astrocyte cultures from G93A-SOD1 transgenic mice were exposed to: xanthine/xanthine oxidase; hydrogen peroxide; A23187 and 3-morpholinosydonimine. Cell viability was measured using the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Neither C6 glioma cells nor cortical astrocytes expressing mutant SOD1 were more susceptible to any of the free radical generating systems compared to control cells. These results suggest that astrocytes are resistant to the toxic effects of mutant SOD1 widely reported for neuronal cells.
自由基损伤与运动神经元病（MND）的病理生理学有关；已在编码铜/锌超氧化物歧化酶（SOD1）的基因中发现突变。有证据表明神经胶质细胞功能障碍可能导致运动神经元损伤，但神经胶质细胞在MND中的具体作用尚未确定。本研究的目的是确定突变型SOD1的表达是否会影响神经胶质细胞对氧化应激的反应。将表达突变型SOD1的稳定C6胶质瘤细胞和来自G93A-SOD1转基因小鼠的皮质星形胶质细胞培养物暴露于：黄嘌呤/黄嘌呤氧化酶；过氧化氢；A23187和3-吗啉代辛二亚胺。使用3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐法测量细胞活力。与对照细胞相比，表达突变型SOD1的C6胶质瘤细胞和皮质星形胶质细胞对任何一种自由基生成系统均没有更高的敏感性。这些结果表明，星形胶质细胞对广泛报道的神经元细胞中突变型SOD1的毒性作用具有抗性。
