Draczynska-Lusiak B, Chen Y M, Sun A Y
Department of Pharmacology, University of Missouri, Columbia 65212, USA.
Neuroreport. 1998 Feb 16;9(3):527-32. doi: 10.1097/00001756-199802160-00028.
Oxidative stress in the central nervous system may cause oxidation of lipoproteins. The oxidized lipoproteins may in turn damage cellular and subcellular membranes and other biomolecules, leading to tissue injury and cell death. Recently, we have demonstrated that oxidized LDL and VLDL induced cell death in a dose-dependent manner. The present study examined the possible signal transduction cascade leading to cell death by oxLDL and oxVLDL in PC12 cells. Using the electrophoretic mobility shift assay, we found that both oxLDL and oxVLDL activated the binding of NF-kappaB to the consensus sequence in the promoter region of the target genes, followed by apopototic cell death. Resveratrol protects the cells from both the activation of NF-kappa-B/ DNA binding activity and apoptotic cell death. Results indicated that oxidized lipoproteins may serve as an oxidative mediator and may activate apoptosis through a nuclear signalling pathway contributing to the pathology in Alzheimer's disease.
中枢神经系统中的氧化应激可能导致脂蛋白氧化。氧化的脂蛋白进而可能损害细胞膜、亚细胞膜及其他生物分子，导致组织损伤和细胞死亡。最近，我们已证明氧化型低密度脂蛋白（oxLDL）和氧化型极低密度脂蛋白（oxVLDL）以剂量依赖的方式诱导细胞死亡。本研究检测了在PC12细胞中由oxLDL和oxVLDL导致细胞死亡的可能信号转导级联反应。使用电泳迁移率变动分析，我们发现oxLDL和oxVLDL均激活了核因子κB（NF-κB）与靶基因启动子区域共有序列的结合，随后发生凋亡性细胞死亡。白藜芦醇可保护细胞免受NF-κB/DNA结合活性的激活及凋亡性细胞死亡的影响。结果表明，氧化的脂蛋白可能作为一种氧化介质，并可能通过核信号通路激活细胞凋亡，这与阿尔茨海默病的病理过程有关。
