Disruption of GluR2/GAPDH Complex Interaction by TAT-GluR2 NT1-3-2 Peptide Protects against Neuronal Death Induced by Epilepsy
Disruption of GluR2/GAPDH Complex Interaction by TAT-GluR2 NT1-3-2 Peptide Protects against Neuronal Death Induced by Epilepsy
复制标题
TAT-GluR2 NT1-3-2 肽破坏 GluR2/GAPDH 复合物相互作用可防止癫痫引起的神经元死亡
DOI：
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发表时间：
2018
影响因子：
0.8
通讯作者：
王纪文
中科院分区：
文献类型：
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作者：
米青;王纪文
Objective.癫痫引起的兴奋毒性神经元死亡与 *-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）受体有关。AMPA受体的Te GluR 2亚基。AMPAR（AMPARs）可以与甘油醛-3-磷酸脱氢酶（GAPDH）结合。Te GluR 2/GAPDH复合物在刺激AMPAR后共内化，这可能参与癫痫的发展。在这项研究中，我们假设用干扰肽破坏GluR 2/GAPDH相互作用将保护体内神经元免受损伤。方法.用盐酸毛果芸香碱诱发大鼠癫痫模型。合成TAT-GluR 2NT 1 -3-2肽以阻断GluR 2与GAPDH之间的相互作用。Fluoro-Jade B染色和TUNEL染色检测经肽干预后神经元的变性和凋亡。通过免疫共沉淀和western-blot分析证实该肽干扰了GluR 2和GAPDH之间的相互作用。结果..肽干扰后癫痫发作时间延长。结论是干扰肽的施用能够显著减少神经元的变性和凋亡。匹罗卡品致痫大鼠海马内TeGluR 2/GAPDH相互作用和GAPDH核表达上调。结论GluR 2/GAPDH的破坏interaction.by施用干扰肽保护免受剂量依赖性的尿素诱导的神经元损伤。因此，GluR 2/GAPDH相互作用可能成为癫痫治疗的新靶点。
Objective. Excitotoxic neuronal death induced by epilepsy is associated with *-amino-3-.hydroxyl-5-methylisoxazole-4-propionate acid (AMPA) receptors. Te GluR2 subunit of AMPA receptors.(AMPARs) may bind with glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Te GluR2/GAPDH.complex co-internalizes upon stimulation of AMPARs, which might be involved in the development of.epilepsy. In this research, we hypothesized that disruption of the GluR2/GAPDH interaction with an.interfering peptide would protect against neuronal damage in vivo. Methods. Rat models of epilepsy were.induced by pilocarpine hydrochloride. TAT-GluR2NT1-3-2 peptide was synthesized to block interaction.between GluR2 and GAPDH. Fluoro-Jade B and TUNEL staining were used to detect degeneration and.apoptosis of neurons after interference by the peptide. Co-immunoprecipitation assay and western-blot.was performed to confrm that the peptide disturbed interactions between GluR2 and GAPDH. Results..Te time of epileptic seizure was found to be delayed after peptide interference. It was concluded that administration of an interfering peptide is able to signifcantly reduce degeneration and apoptosis of neurons..Te GluR2/GAPDH interaction and GAPDH nuclear expression were upregulated in the hippocampus of.rats subjected to pilocarpine-induced seizures. Conclusion. Disruption of the GluR2/GAPDH interaction.by administration of an interfering peptide protects against seizure-induced neuronal damage that is dose.dependent. Tus, the GluR2/GAPDH interaction may be a novel therapeutic target for development of.treatment for epilepsy.