Mronga Thomas, Stahnke Thomas, Goldbaum Olaf, Richter-Landsberg Christiane
Department of Biology, Molecular Neurobiology, University of Oldenburg, Oldenburg, Germany.
Glia. 2004 May;46(4):446-55. doi: 10.1002/glia.20022.
Oligodendrocytes, the myelin-forming cells of the CNS, are specifically sensitive to oxidative stress and respond by the onset of programmed cell death (PCD). To further unravel the molecular events underlying their enhanced susceptibility, we have investigated whether mitochondrial damage occurs during oxidative stress-induced PCD in cultured rat brain oligodendrocytes. Mitochondria are considered as a central control point of apoptosis, and mitochondrial dysfunction has been linked to neurodegenerative disease. Upon a number of stimuli through the release of cytochrome c, they coordinate caspase activation, causing morphological and biochemical changes associated with PCD. Oxidative stress was exerted by the application of hydrogen peroxide. The data show that hydrogen peroxide-induced apoptosis in oligodendrocytes involves mitochondrial damage and cytochrome c release and is accompanied by the activation of the death-related caspases 3 and 9. Concomitantly, the activation and nuclear translocation of extracellular signal regulated kinases ERK1,2 are observed, which have been implicated to participate in the regulation of cell death and survival. DNA fragmentation could not be attenuated by the ERK1,2 inhibitor PD 98059, indicating that the ERK1,2- pathway in oligodendrocytes may be involved in the initial survival response after exposure to stressful stimuli.
少突胶质细胞是中枢神经系统中形成髓鞘的细胞，对氧化应激特别敏感，并通过程序性细胞死亡（PCD）的启动做出反应。为了进一步揭示其易感性增强背后的分子事件，我们研究了在培养的大鼠脑少突胶质细胞中，氧化应激诱导的PCD过程中是否发生线粒体损伤。线粒体被认为是细胞凋亡的中心控制点，线粒体功能障碍与神经退行性疾病有关。在通过细胞色素c释放产生多种刺激后，它们协调半胱天冬酶的激活，导致与PCD相关的形态和生化变化。通过施加过氧化氢来施加氧化应激。数据表明，过氧化氢诱导的少突胶质细胞凋亡涉及线粒体损伤和细胞色素c释放，并伴随着与死亡相关的半胱天冬酶3和9的激活。同时，观察到细胞外信号调节激酶ERK1、2的激活和核转位，它们被认为参与细胞死亡和存活的调节。ERK1、2抑制剂PD 98059不能减弱DNA片段化，表明少突胶质细胞中的ERK1、2途径可能参与应激刺激暴露后的初始存活反应。
