Overexpression of C-terminal fragment of glutamate receptor 6 prevents neuronal injur y in kainate-induced seizure v ia disassembly of GluR6-PSD95-MLK3 signaling module
Jie Mou
Xiaomei Liu
Dongsheng Pei
摘要：Our previous study showed that when glutamate receptor (GluR)6 C terminus-containing pep-tide conjugated with the human immunodeficiency virus Tat protein (GluR6)-9c is delivered into hippocampal neurons in a brain ischemic model, the activation of mixed lineage kinase 3 (MLK3) and c-Jun NH2-terminal kinase (JNK) is inhibited via GluR6-postsynaptic density pro-tein 95 (PSD95). In the present study, we investigated whether the recombinant adenovirus (Ad) carrying GluR6c could suppress the assembly of the GluR6-PSD95-MLK3 signaling module and decrease neuronal cell death induced by kainate in hippocampal CA1 subregion. A seizure model in Sprague-Dawley rats was induced by intraperitoneal injections of kainate. The effect of Ad-Glur6-9c on the phosphorylation of JNK, MLK3 and mitogen-activated kinase kinase 7 (MKK7) was observed with western immunoblots and immunohistochemistry. Our findings revealed that overexpression of GluR6c inhibited the interaction of GluR6 with PSD95 and prevented the kainate-induced activation of JNK, MLK3 and MKK7. Furthermore, kainate-mediated neuronal cell death was signiifcantly suppressed by GluR6c. Taken together, GluR6 may play a pivotal role in neuronal cell death.
机标关键词：cell deathhuman immunodeficiency virusrecombinant adenovirushippocampal neuronsglutamate receptorTat protein
资助基金：the National Natural Science Foundation of China, (No.30800309,81372172)the Educational Science Foundation of Jiangsu Province, China, (No.10KJB350005)the Xuzhou Science Foundation in China, (No. XZZD1153)the President Special Grant of Xuzhou Medical College in China, (No.09KJZ20)
论文发表日期：2014-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：7( 2059-2065 )
英文信息