Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, 663-8501, Japan.
Neurochem Res. 2010 May;35(5):712-7. doi: 10.1007/s11064-010-0124-4. Epub 2010 Jan 23.
The present study aimed at understanding the effect of the linoleic acid derivative 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA) on oxidative stress-induced neuronal death. Sodium nitroprusside (SNP; 1 mM) reduced viability of cultured rat cerebral cortical neurons to 50% of basal levels, but DCP-LA significantly prevented the SNP effect in a concentration (1-100 nM)-dependent manner. In addition, DCP-LA (100 nM) rescued neurons from SNP-induced degradation. SNP (1 mM) activated caspase-3 and -9 in cultured rat cerebral cortical neurons, but DCP-LA (100 nM) abolished the caspase activation. For a mouse model of middle cerebral artery occlusion, oral administration with DCP-LA (1 mg/kg) significantly diminished degraded area due to cerebral infarction. The results of the present study, thus, demonstrate that DCP-LA protects neurons at least in part from oxidative stress-induced apoptosis by inhibiting activation of caspase-3/-9.
本研究旨在探讨亚油酸衍生物 8-[2-(2-戊基-环丙基甲基)-环丙基]-辛酸（DCP-LA）对氧化应激诱导的神经元死亡的影响。硝普钠（SNP；1mM）将培养的大鼠皮质神经元的活力降低至基础水平的 50%，但 DCP-LA 以浓度（1-100nM）依赖性方式显著预防了 SNP 的作用。此外，DCP-LA（100nM）可挽救 SNP 诱导的神经元降解。SNP（1mM）激活了培养的大鼠皮质神经元中的 caspase-3 和 -9，但 DCP-LA（100nM）可消除 caspase 的激活。对于大脑中动脉闭塞的小鼠模型，DCP-LA（1mg/kg）的口服给药可显著减少因脑梗死引起的降解面积。因此，本研究的结果表明，DCP-LA 通过抑制 caspase-3/-9 的激活，至少部分保护神经元免受氧化应激诱导的细胞凋亡。
