Juurlink B H, Thorburne S K, Hertz L
Department of Anatomy and Cell Biology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Glia. 1998 Apr;22(4):371-8. doi: 10.1002/(sici)1098-1136(199804)22:4<371::aid-glia6>3.0.co;2-6.
Previous work showed that the susceptibility of oligodendroglial progenitors to oxidative stress is related to their low reduced-glutathione (GSH) and high iron contents. This suggests that these cells have a poor ability to scavenge peroxides. All peroxides are scavenged by glutathione peroxidase. Glutathione peroxidase activity requires GSH as an electron donor resulting in the formation of oxidized-glutathione. Cellular GSH content is dependent upon synthesis as well as reduction of oxidized-glutathione. The objectives of the present study were to compare several parameters important in the ability to scavenge peroxides between astrocytes and oligodendroglia. Three stages of oligodendroglial differentiation were examined: the proliferative oligodendrocyte progenitor, the proliferative oligodendroblast, and the post-mitotic oligodendrocyte. We demonstrate that oligodendroglia at all stages of differentiation have less than one-half the content of GSH compared to astrocytes. This low level of GSH is due in part to a lower rate of GSH synthesis in oligodendroglia compared to astrocytes and in part to their having only one-half of the glutathione reductase activity of astrocytes. Glutathione peroxidase activity of oligodendroglia is less than 15% of that found in astrocytes. The low GSH and concomitant low glutathione peroxidase activity would tend to maintain peroxides at levels that are dangerously high if iron is released from iron stores. Oligodendroglia have high iron stores, and thus these findings emphasize how vulnerable the oligodendroglial lineage is to perturbations that result in oxidative stress.
先前的研究表明，少突胶质前体细胞对氧化应激的易感性与其低水平的还原型谷胱甘肽（GSH）和高含量的铁有关。这表明这些细胞清除过氧化物的能力较差。所有过氧化物均由谷胱甘肽过氧化物酶清除。谷胱甘肽过氧化物酶活性需要GSH作为电子供体，从而导致氧化型谷胱甘肽的形成。细胞内GSH含量取决于其合成以及氧化型谷胱甘肽的还原。本研究的目的是比较星形胶质细胞和少突胶质细胞在清除过氧化物能力方面的几个重要参数。研究了少突胶质细胞分化的三个阶段：增殖性少突胶质前体细胞、增殖性少突胶质母细胞和有丝分裂后少突胶质细胞。我们证明，与星形胶质细胞相比，处于所有分化阶段的少突胶质细胞的GSH含量均不到其一半。这种低水平的GSH部分归因于与星形胶质细胞相比，少突胶质细胞中GSH合成速率较低，部分归因于其谷胱甘肽还原酶活性仅为星形胶质细胞的一半。少突胶质细胞的谷胱甘肽过氧化物酶活性不到星形胶质细胞的15%。如果铁从铁储存中释放出来，低水平的GSH和随之而来的低谷胱甘肽过氧化物酶活性往往会使过氧化物维持在危险的高水平。少突胶质细胞有大量的铁储存，因此这些发现强调了少突胶质细胞谱系对导致氧化应激的干扰是多么脆弱。
