Thorburne S K, Juurlink B H
Department of Anatomy and Cell Biology, University of Saskatchewan, Saskatoon, Canada.
J Neurochem. 1996 Sep;67(3):1014-22. doi: 10.1046/j.1471-4159.1996.67031014.x.
We have previously shown, using qualitative approaches, that oligodendroglial precursors are more readily damaged by free radicals than are astrocytes. In the present investigation we quantified the oxidative stress experienced by the cells using oxidation of dichlorofluorescin diacetate to dichlorofluorescein as a measure of oxidative stress; furthermore, we have delineated the physiological bases of the difference in susceptibility to oxidative stress found between oligodendroglial precursors and astrocytes. We demonstrate that (a) oligodendroglial precursors under normal culture conditions are under six times as much oxidative stress as astrocytes, (b) oxidative stress experienced by oligodendroglial precursors increases sixfold when exposed to 140 mW/m2 of blue light, whereas astrocytic oxidative stress only doubles, (c) astrocytes have a three times higher concentration of GSH than oligodendroglial precursors, (d) oligodendroglial precursors have > 20 times higher iron content than do astrocytes, and (e) oxidative stress in oligodendroglial precursors can be prevented either by chelating intracellular free iron or by raising intracellular GSH levels to astrocytic values. We conclude that GSH plays a central role in preventing free radical-mediated damage in glia.
我们之前通过定性方法表明，少突胶质前体细胞比星形胶质细胞更容易受到自由基的损伤。在本研究中，我们使用二氯荧光素二乙酸酯氧化为二氯荧光素的方法来量化细胞所经历的氧化应激，以此作为氧化应激的一种衡量指标；此外，我们还阐述了少突胶质前体细胞和星形胶质细胞在氧化应激易感性方面存在差异的生理基础。我们证明：（a）在正常培养条件下，少突胶质前体细胞所承受的氧化应激是星形胶质细胞的六倍；（b）当暴露于140 mW/m2的蓝光下时，少突胶质前体细胞所经历的氧化应激增加六倍，而星形胶质细胞的氧化应激仅增加一倍；（c）星形胶质细胞的谷胱甘肽（GSH）浓度比少突胶质前体细胞高三倍；（d）少突胶质前体细胞的铁含量比星形胶质细胞高20倍以上；（e）通过螯合细胞内游离铁或将细胞内GSH水平提高到星形胶质细胞的水平，可以预防少突胶质前体细胞中的氧化应激。我们得出结论，GSH在预防神经胶质细胞中自由基介导的损伤方面起着核心作用。
