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

Ko, HW; Park, KY; Kim, H; Han, PL; Kim, YU; Gwag, BJ; Choi, EJ
Journal of neurochemistry, 71(4):1390-1395, 1998
Journal Title
Journal of neurochemistry
We examined the possibility that c-Jun N-terminal kinase (JNK) and nuclear factor kappaB (NF-kappaB) might be involved in intracellular signaling cascades that mediate NMDA-initiated neuronal events. Exposure of cortical neurons to 100 microM 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 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-kappaB antibody demonstrated nuclear translocation of NF-kappaB within 5 min following NMDA treatment. NMDA treatment also enhanced the DNA binding activity of nuclear NF-kappaB in a Ca2+-dependent manner. Treatment with 3 mM aspirin blocked the NMDA-induced activation of JNK and NF-kappaB. Neuronal death following a brief exposure to 100 microM 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-kappaB 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-kappaB and JNK.
MeSH terms
AnimalsAspirin/pharmacologyCalcium/*physiologyCalcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors/*metabolismCells, CulturedCerebral Cortex/cytology/*enzymology/*metabolismEnzyme Activation/drug effectsFetusJNK Mitogen-Activated Protein KinasesMice*Mitogen-Activated Protein KinasesN-Methylaspartate/antagonists & inhibitors/*pharmacologyNF-kappa B/antagonists & inhibitors/*metabolism
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Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
AJOU Authors
곽, 병주
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