Laboratory of Food and Biodynamics, Graduate School of Bioagricultural Science, Nagoya University, Nagoya 464-8601, Japan.
J Clin Biochem Nutr. 2008 Jul;43(1):26-33. doi: 10.3164/jcbn.2008040.
During the lipid peroxidation reaction, lipid hydroperoxides are formed as primary products. Several lines of evidence suggest that lipid hydroperoxides can trigger cell death in many cell types, including neurons. In a screening of lipid hydroperoxides which can induce toxicity in neuronal cells, we found docosahexaenoic acid hydroperoxides (DHA-OOH) induced much severe levels of reactive oxygen species generation and cell death in human neuroblastoma SH-SY5Y cells compared to the hydroperoxides of linoleic acid and arachidonic acid. Therefore, we focused on DHA-OOH, and demonstrated that DHA-OOH apparently induced an apoptosis in the neuronal cells through several apoptotic hallmarks including nuclei condensation, DNA fragmentation, poly (ADP-ribose) polymerase cleavage and increased activity of caspase-3. We also found the signaling changes in mitochondria-mediated apoptosis, such as cytochrome c release and increased expression of Bcl-2, as well as a dose-dependent attenuation of mitochondrial membrane potential in the DHA-OOH treated cells. These data indicated DHA hydroperoxide as a potential inducer of apoptosis in human neuroblastoma SH-SY5Y cells, which may be mediated by mitochondria dysfunction pathway.
在脂质过氧化反应中，脂质氢过氧化物是主要产物。有几条证据表明，脂质氢过氧化物可以引发许多细胞类型的细胞死亡，包括神经元。在筛选可以诱导神经元细胞毒性的脂质氢过氧化物的过程中，我们发现二十二碳六烯酸氢过氧化物（DHA-OOH）在人神经母细胞瘤 SH-SY5Y 细胞中引起的活性氧生成和细胞死亡水平比亚油酸和花生四烯酸的氢过氧化物严重得多。因此，我们专注于 DHA-OOH，并证明 DHA-OOH 通过几种凋亡特征，包括核浓缩、DNA 片段化、多聚（ADP-核糖）聚合酶切割和 caspase-3 活性增加，明显诱导神经元细胞凋亡。我们还发现了线粒体介导的凋亡中的信号变化，如细胞色素 c 释放和 Bcl-2 表达增加，以及 DHA-OOH 处理细胞中线粒体膜电位的剂量依赖性衰减。这些数据表明 DHA 氢过氧化物是人类神经母细胞瘤 SH-SY5Y 细胞凋亡的潜在诱导剂，可能通过线粒体功能障碍途径介导。
