Ca2+-mediated activation of c-Jun N-terminal kinase and nuclear factor κB by NMDA in cortical cell cultures

Hyuk Wan Ko, Kye Yoon Park, Hansin Kim, Pyung Lim Han, Youn Uck Kim, Byoung Joo Gwag, Eui Ju Choi

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

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 μM NMDA induced activation of JNK within 1 min. Activity of JNK was further increased over the next 5 rain and then declined by 30 min. Similarly, ionomycin, a selective Ca2+ ionophore, induced activation of JNK. The NMDA-induced activation of JNK was abrogated in the absence of extracellular Ca2+, suggesting that Ca2+ 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 Ca2+-dependent manner. Treatment with 3 mM aspirin blocked the NMDA-induced activation of JNK and NF-κB. Neuronal death following a brief exposure to 100 μM NMDA was Ca2+ dependent and attenuated by addition of aspirin or sodium salicylate. The present study suggests that Ca2+ 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.

Original languageEnglish
Pages (from-to)1390-1395
Number of pages6
JournalJournal of Neurochemistry
Volume71
Issue number4
DOIs
Publication statusPublished - 1998 Oct

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

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