Chen Jing, Zheng Guo, Guo Hu, Shi Zhong-Nan
Department of Neurology, Nanjing Children's Hospital, Nanjing Medical University, No. 72, Guangzhou Road, Gu Lou District, Nanjing, Jiangsu, 210008, People's Republic of China,
J Mol Neurosci. 2014 Aug;53(4):677-83. doi: 10.1007/s12031-014-0236-4. Epub 2014 Jan 23.
Endoplasmic reticulum (ER) stress may play a role in status epilepticus (SE). Sprague-Dawley rats were randomized into three groups: control (saline), SE (pentylenetetrazol), and dentate gyrus (DG), pretreated with 2-deoxy-D-glucose (2-DG). Expression levels of glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), eukaryotic initiation factor 2α (eIF2α), and protein kinase RNA-like ER kinase (PERK) were determined. CHOP messenger RNA (mRNA) and protein expression levels in SE group were significantly increased as compared to the control group (P < 0.0001), and significantly decreased in DG group as compared to the SE group (P < 0.0001). Phosphorylated eIF-2α protein expression level in SE group was significantly increased as compared to the control group (P < 0.0001) and significantly decreased in DG group as compared to the SE group (P < 0.0001). GRP messenger RNA expression levels and protein levels in SE group was significantly increased as compared to the control group (P < 0.0001) and significantly decreased in DG group as compared to the SE group (P < 0.0001). Phosphorylated PERK protein expression level in SE group was significantly increased as compared to the control group (P < 0.0001), and significantly decreased in DG group as compared to the SE group (P < 0.0001) at the time of 12 and 24 h. Our results suggest that brain injury from SE might involve ER stress via the pro-apoptotic PERK-eIF2α-CHOP signaling pathway.
内质网（ER）应激可能在癫痫持续状态（SE）中起作用。将Sprague-Dawley大鼠随机分为三组：对照组（生理盐水）、SE组（戊四氮）和齿状回（DG）组，预先用2-脱氧-D-葡萄糖（2-DG）处理。测定葡萄糖调节蛋白78（GRP78）、CCAAT/增强子结合蛋白同源蛋白（CHOP）、真核起始因子2α（eIF2α）和蛋白激酶RNA样内质网激酶（PERK）的表达水平。与对照组相比，SE组中CHOP信使核糖核酸（mRNA）和蛋白表达水平显著升高（P < 0.0001），与SE组相比，DG组中CHOP信使核糖核酸和蛋白表达水平显著降低（P < 0.0001）。与对照组相比，SE组中磷酸化eIF-2α蛋白表达水平显著升高（P < 0.0001），与SE组相比，DG组中磷酸化eIF-2α蛋白表达水平显著降低（P < 0.0001）。与对照组相比，SE组中GRP信使核糖核酸表达水平和蛋白水平显著升高（P < 0.0001），与SE组相比，DG组中GRP信使核糖核酸表达水平和蛋白水平显著降低（P < 0.0001）。在12小时和24小时时，与对照组相比，SE组中磷酸化PERK蛋白表达水平显著升高（P < 0.0001），与SE组相比，DG组中磷酸化PERK蛋白表达水平显著降低（P < 0.0001）。我们的结果表明，SE引起的脑损伤可能通过促凋亡的PERK-eIF2α-CHOP信号通路涉及内质网应激。
