Glutamate activates NF-κB through calpain in neurons

Marion N. Schölzke, Ioana Potrovita, Srinivasa Subramaniam, Simone Prinz, Markus Schwaninger*

*Corresponding author for this work
62 Citations (Scopus)


Glutamate induces gene transcription in numerous physiological and pathological conditions. Among the glutamate-responsive transcription factors, NF-κB has been mainly implicated in neuronal survival and death. Recent data also suggest a role of NF-κB in neural development and memory formation. In non-neuronal cells, degradation of the inhibitor IκBα represents a key step in NF-κB activation. However, little is known of how glutamate activates NF-κB in neurons. To investigate thesignalling cascade involved we used primary murine cerebellar granule cells. Glutamate induced a rapid reduction of IκBα levels and nuclear translocation of the NF-κB subunit p65. The glutamate-induced reduction of IκBα levels was blocked by the N-methyl-D-aspartate inhibitor MK801. Specific inhibitors of the proteasome, caspase 3, and the phosphoinositide 3-kinase had no effect on glutamate-induced IκKBα degradation. However, inhibition of the glutamate-activated Ca2+-dependent protease calpain by calpeptin completely blocked IκBα degradation and reduced the nuclear translocation of p65. Calpeptin also partially blocked glutamate-induced cell death. Our data indicate that the Ca2+- dependent protease calpain is involved in the NF-κB activation in neurons in response to M-methyl-D-aspartate receptor occupancy by glutamate. NF-κB activation by calpain may mediate the long-term effects of glutamate on neuron survival or memory formation.

Original languageEnglish
JournalEuropean Journal of Neuroscience
Issue number12
Pages (from-to)3305-3310
Number of pages6
Publication statusPublished - 01.12.2003

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)


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