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Ca 2+ ‐Mediated Activation of c‐Jun N‐Terminal Kinase and Nuclear Factor κB by NMDA in Cortical Cell Cultures
Author(s) -
Ko Hyuk Wan,
Park KyeYoon,
Kim Hansin,
Han PyungLim,
Kim Youn Uck,
Gwag Byoung Joo,
Choi EuiJu
Publication year - 1998
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 - 10.1046/j.1471-4159.1998.71041390.x
Subject(s) - nmda receptor , neuroprotection , ionomycin , kinase , neurotoxicity , chemistry , microbiology and biotechnology , intracellular , biology , neuroscience , biochemistry , receptor , toxicity , organic chemistry
We examined the possibility that c‐Jun N‐terminal kinase (JNK) and nuclear factor κB (NF‐κB) might be involved in intracellular signaling cascades that mediate NMDA‐initiated neuronal events. Exposure of cortical neurons to 100 µ M NMDA induced activation of JNK within 1 min. Activity of JNK was further increased over the next 5 min and then declined by 30 min. Similarly, ionomycin, a selective Ca 2+ ionophore, induced activation of JNK. The NMDA‐induced activation of JNK was abrogated in the absence of extracellular Ca 2+ , suggesting that Ca 2+ entry is necessary and sufficient for the JNK activation. Immunohistochemistry with anti‐NF‐κB antibody demonstrated nuclear translocation of NF‐κB within 5 min following NMDA treatment. NMDA treatment also enhanced the DNA binding activity of nuclear NF‐κB in a Ca 2+ ‐dependent manner. Treatment with 3 m M aspirin blocked the NMDA‐induced activation of JNK and NF‐κB. Neuronal death following a brief exposure to 100 µ M NMDA was Ca 2+ dependent and attenuated by addition of aspirin or sodium salicylate. The present study suggests that Ca 2+ influx is required for NMDA‐induced activation of JNK and NF‐κB as well as NMDA neurotoxicity. This study also implies that aspirin may exert its neuroprotective action against NMDA through blocking the NMDA‐induced activation of NF‐κB and JNK.