Xie Nanchang, Wang Cui, Wu Chuanjie, Cheng Xuan, Gao Yanlun, Zhang Haifeng, Zhang Yi, Lian Yajun
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People's Republic of China.
Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.
Neurochem Res. 2016 Jun;41(6):1335-42. doi: 10.1007/s11064-016-1835-y. Epub 2016 Jan 22.
Mitochondrial division inhibitor 1 (mdivi-1), a selective inhibitor of the mitochondrial fission protein dynamin-related protein 1, has been proposed to have a neuroprotective effect on hippocampal neurons in animal models of epilepsy. However, the effect of mdivi-1 on epileptic neuronal death in vitro remains unknown. Therefore, we investigated the effect of mdivi-1 and the underlying mechanisms in the hippocampal neuronal culture (HNC) model of acquired epilepsy (AE) in vitro. We found that mitochondrial fission was increased in the HNC model of AE and inhibition of mitochondrial fission by mdivi-1 significantly decreased neuronal apoptosis induced by AE. In addition, mdivi-1 pretreatment significantly attenuated oxidative stress induced by AE characterized by decrease of reactive oxygen species (ROS) production and malondialdehyde level and by increase of superoxide dismutase activity. Moreover, mdivi-1 pretreatment significantly decreased endoplasmic reticulum (ER) stress markers glucose-regulated protein 78, C/EBP homologous protein expression and caspase-3 activation. Altogether, our findings suggest that mdivi-1 protected against AE-induced hippocampal neuronal apoptosis in vitro via decreasing ROS-mediated oxidative stress and ER stress.
线粒体分裂抑制剂1（mdivi-1）是线粒体分裂蛋白动力相关蛋白1的选择性抑制剂，在癫痫动物模型中已被证明对海马神经元具有神经保护作用。然而，mdivi-1对体外癫痫神经元死亡的影响尚不清楚。因此，我们在体外获得性癫痫（AE）的海马神经元培养（HNC）模型中研究了mdivi-1的作用及其潜在机制。我们发现，在AE的HNC模型中线粒体分裂增加，mdivi-1抑制线粒体分裂可显著降低AE诱导的神经元凋亡。此外，mdivi-1预处理显著减轻了AE诱导的氧化应激，表现为活性氧（ROS）生成和丙二醛水平降低，超氧化物歧化酶活性增加。此外，mdivi-1预处理显著降低了内质网（ER）应激标志物葡萄糖调节蛋白78、C/EBP同源蛋白表达和半胱天冬酶-3激活。总之，我们的研究结果表明，mdivi-1通过降低ROS介导的氧化应激和ER应激，在体外对AE诱导的海马神经元凋亡具有保护作用。
