Vogt M, Bauer M K, Ferrari D, Schulze-Osthoff K
Department of Internal Medicine I, Medical Clinics, Eberhard-Karls-University, Tübingen, Germany.
FEBS Lett. 1998 Jun 5;429(1):67-72. doi: 10.1016/s0014-5793(98)00562-6.
Apoptosis plays an important role in neurodegeneration, although the mechanisms and mediators in the brain are largely unknown. Because microglial cells have been suggested to contribute to apoptosis in neurological disorders, we investigated the expression of the death ligand CD95L in this cell type. We found that, compared to classical mediators of microglial activation, the most potent inducer of CD95L was oxidative stress. Exposure of microglial cells to H2O2 or paraquat rapidly triggered CD95L mRNA and protein expression, associated with the activation of transcription factor NF-kappaB. Enhanced expression of CD95L was further found following exposure of cells to hypoxia and subsequent reoxygenation. Our results indicate a potential role of CD95L in oxidative stress-mediated cell death, ischemia/reperfusion and other diseases with a disturbed redox balance.
细胞凋亡在神经退行性变中起重要作用，尽管大脑中的机制和介质在很大程度上尚不清楚。由于有人提出小胶质细胞在神经疾病中促成细胞凋亡，我们研究了这种细胞类型中死亡配体CD95L的表达。我们发现，与小胶质细胞激活的经典介质相比，CD95L最有效的诱导剂是氧化应激。将小胶质细胞暴露于过氧化氢或百草枯会迅速触发CD95L mRNA和蛋白质表达，这与转录因子NF-κB的激活有关。在细胞暴露于缺氧及随后的复氧后，进一步发现CD95L表达增强。我们的结果表明CD95L在氧化应激介导的细胞死亡、缺血/再灌注及其他氧化还原平衡紊乱的疾病中具有潜在作用。
