Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8503, Japan.
Eur J Pharmacol. 2011 Jan 15;650(2-3):544-9. doi: 10.1016/j.ejphar.2010.10.028. Epub 2010 Oct 20.
Amyloid-β peptide (Aβ) has been implicated in the pathogenesis of Alzheimer's disease (AD). It can cause cell death in Alzheimer's disease by evoking a cascade of oxidative damage to neurons. Antioxidant compounds may help to elucidate and develop a treatment for Alzheimer's disease. In the present study, we investigated the protective effect of TEMPOL (4-hydroxy-2,2,6,6-tetramethyl-1-piperidinyloxy), a cyclic nitroxide which is particularly effective at reducing oxidative injury, on Aβ(1-42)-induced SH-SY5Y cell toxicity. Exposure of cells to 20 μM Aβ(1-42) for 48 h caused viability loss and apoptotic increase, and pre-treatment with TEMPOL for 24 h significantly reduced the viability loss and apoptotic rate. In addition, TEMPOL inhibited Aβ(1-42)-induced superoxide anion generation and hydroxyl radical generation to a striking degree. Based on these results, it is concluded that TEMPOL effectively protects SH-SY5Y cells against β-amyloid-induced damage by suppressing the generation of reactive oxygen species especially, superoxide anion.
β淀粉样肽(Aβ)与阿尔茨海默病(AD)的发病机制有关。它可以通过引发一连串的神经元氧化损伤导致细胞死亡。抗氧化化合物可能有助于阐明和开发阿尔茨海默病的治疗方法。在本研究中,我们研究了 TEMPOL(4-羟基-2,2,6,6-四甲基-1-哌啶氧自由基)的保护作用,TEMPOL 是一种环状氮氧化物,特别有效地减少氧化损伤,对 Aβ(1-42)诱导的 SH-SY5Y 细胞毒性的影响。细胞暴露于 20 μM Aβ(1-42)48 小时会导致活力丧失和凋亡增加,而 TEMPOL 预处理 24 小时可显著降低活力丧失和凋亡率。此外,TEMPOL 显著抑制 Aβ(1-42)诱导的超氧阴离子生成和羟基自由基生成。基于这些结果,可以得出结论,TEMPOL 通过抑制活性氧特别是超氧阴离子的生成,有效保护 SH-SY5Y 细胞免受β-淀粉样肽诱导的损伤。