Overexpression of C-terminal fragment of glutamate receptor 6 prevents neuronal injury in kainate-induced seizure via disassembly of Glu R6-PSD95-MLK3 signaling module  

作　　者：Jie Mou Xiaomei Liu Dongsheng Pei 

机构地区：[1]Jiangsu Key Laboratory of Targeted Drug and Clinical Application, Xuzhou Medical College [2]School of Basic Medical Science, Xuzhou Medical College [3]Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College

出　　处：《Neural Regeneration Research》2014年第23期2059-2065,共7页中国神经再生研究（英文版）

基　　金：supported by 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;a grant from the Zhenxing Project Foundation of XZMC

摘　　要：Our previous study showed that when glutamate receptor （GluR）6 C terminus-containing peptide 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 protein 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 INK, MLK3 and mitogen-activated ldnase 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 INK, MLK3 and MKK7. Furthermore, kainate-mediated neuronal cell death was significantly suppressed by GluR6c. Taken together, GluR6 may play a pivotal role in neuronal cell death.Our previous study showed that when glutamate receptor （GluR）6 C terminus-containing peptide 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 protein 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 INK, MLK3 and mitogen-activated ldnase 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 INK, MLK3 and MKK7. Furthermore, kainate-mediated neuronal cell death was significantly suppressed by GluR6c. Taken together, GluR6 may play a pivotal role in neuronal cell death.

关 键 词：nerve regeneration brain injury hippocampal neuronal injury seizures ADENOVIRUS GLUR6 PSD95 MLK3 KAINATE apoptosis JNK NSFC grants neural regeneration 

分 类 号：R742.1[医药卫生—神经病学与精神病学]