title: Overexpression of C-terminal fragment of glutamate receptor 6 prevents neuronal injury in kainate-induced seizure via disassembly of GluR6-PSD-95-MLK3 signaling module.
abstract: 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 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 significantly suppressed by GluR6c. Taken together, GluR6 may play a pivotal role in neuronal cell death.
authors: Jiangsu Key Laboratory of Targeted Drug and Clinical Application, Xuzhou Medical College, Xuzhou, Jiangsu Province, China.
authors: Jie
authors: J
authors: Mou
authors: School of Basic Medical Science, Xuzhou Medical College, Xuzhou, Jiangsu Province, China.
authors: Xiaomei
authors: X
authors: Liu
authors: Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou, Jiangsu Province, China.
authors: Dongsheng
authors: D
authors: Pei
keywords: GluR6; JNK; MLK3; NSFC grants; PSD95; adenovirus; apoptosis; brain injury; hippocampal neuronal injury; kainate; nerve regeneration; neural regeneration; seizures
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