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The role of S‐nitrosylation of kainate‐type of ionotropic glutamate receptor 2 in epilepsy induced by kainic acid
Author(s) -
Wang Linxiao,
Liu Yanyan,
Lu Rulan,
Dong Guoying,
Chen Xia,
Yun Wenwei,
Zhou Xianju
Publication year - 2018
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.14266
Subject(s) - kainate receptor , kainic acid , ionotropic effect , epileptogenesis , ampa receptor , glutamate receptor , microbiology and biotechnology , ionotropic glutamate receptor , epilepsy , biology , neuroscience , receptor , chemistry , biochemistry
Epilepsy is a chronic brain disease affecting millions of individuals. Kainate receptors, especially kainate‐type of ionotropic glutamate receptor 2 (GluK2), play an important role in epileptogenesis. Recent data showed that GluK2 could undergo post‐translational modifications in terms of S‐nitrosylation ( SNO ), and affect the signaling pathway of cell death in cerebral ischemia‐reperfusion. However, it is unclear whether S‐nitrosylation of GluK2 ( SNO ‐GluK2) contributes to cell death induced by epilepsy. Here, we report that kainic acid‐induced SNO ‐GluK2 is mediated by GluK2 itself, regulated by neuronal nitric oxide synthase ( nNOS ) and the level of cytoplasmic calcium in vivo and in vitro hippocampus neurons. The whole‐cell patch clamp recordings showed the influence of SNO ‐GluK2 on ion channel characterization of GluK2‐Kainate receptors. Moreover, immunohistochemistry staining results showed that inhibition of SNO ‐GluK2 by blocking nNOS or GluK2 or by reducing the level of cytoplasmic calcium‐protected hippocampal neurons from kainic acid‐induced injury. Finally, immunoprecipitation and western blotting data revealed the involvement of assembly of a GluK2‐ PSD 95‐ nNOS signaling complex in epilepsy. Taken together, our results showed that the SNO ‐GluK2 plays an important role in neuronal injury of epileptic rats by forming GluK2‐ PSD 95‐ nNOS signaling module in a cytoplasmic calcium‐dependent way, suggesting a potential therapeutic target site for epilepsy.