Neural Regeneration Research ›› 2014, Vol. 9 ›› Issue (23): 2059-2065.doi: 10.4103/1673-5374.147932

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Overexpression of C-terminal fragment of glutamate receptor 6 prevents neuronal injury in kainate-induced seizure via disassembly of GluR6-PSD95-MLK3 signaling module

Jie Mou 1, Xiaomei Liu 2, Dongsheng Pei 3   

  1. 1 Jiangsu Key Laboratory of Targeted Drug and Clinical Application, Xuzhou Medical College, Xuzhou, Jiangsu Province, China
    2 School of Basic Medical Science, Xuzhou Medical College, Xuzhou, Jiangsu Province, China
    3 Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou, Jiangsu Province, China
  • Received:2014-09-22 Online:2014-12-10 Published:2014-12-10
  • Contact: Dongsheng Pei, Ph.D., Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China,dspei@xzmc.edu.cn.
  • Supported by:

    This work was 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; and a grant from the Zhenxing Project Foundation of  XZMC.

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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.

Key words: nerve regeneration, brain injury, hippocampal neuronal injury, seizures, adenovirus, GluR6, PSD95, MLK3, kainate, apoptosis, JNK, NSFC grants, neural regeneration