Opposing roles for NF-κB/Rel factors p65 and c-Rel in the modulation of neuron survival elicited by glutamate and interleukin-1β

Marina Pizzi, Francesca Goffi, Flora Boroni, Marina Benarese, Scott E. Perkins, Hsiou Chi Liouand, Pierfranco Spano

Research output: Contribution to journalArticle

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Abstract

The nuclear transcription factors NF-κB/Rel have been shown to function as key regulators of either cell death or survival in neuronal cells. Here, we investigated whether selective activation of diverse NF-κB/Rel family members might lead to distinct effects on neuron viability. In both cultured rat cerebellar granule cells and mouse hippocampal slices, we examined NF-κB/Rel activation induced by two opposing modulators of cell viability: 1) interleukin-1β (IL-1β), which promotes neuron survival and 2) glutamate, which can elicit toxicity. IL-1β produced a prolonged stimulation of NF-κB/Rel factors by inducing both IκBα and IκBβ degradation. Glutamate produced a delayed and transient activation of NF-κB/Rel, which was associated with a brief loss of IκBα. Moreover, IL-1β activated the p50, p65, and c-Rel subunits of NF-κB/Rel, whereas glutamate activated only the p50 and p65 proteins. The inhibition of NF-κB/Rel protein expression by antisense oligonucleotides in cerebellar granule cells showed that p65 was involved in glutamate-mediated cell death, whereas c-Rel was essential for IL-1β-preserved cell survival. Furthermore, the depletion of c-Rel in cultured neurons as well as in the hippocampus from the c-Rel-/- mouse converted the IL-1β effect into toxicity. These findings suggest that, within a single neuron, the balance between cell death and survival in response to external stimuli may rely on the activation of distinct NF-κB/Rel proteins.

Original languageEnglish
Pages (from-to)20717-20723
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number23
DOIs
Publication statusPublished - Jun 7 2002

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Interleukin-1
Neurons
Glutamic Acid
Modulation
Cell Survival
Cell death
Chemical activation
Cell Death
Toxicity
Cells
Proteins
Antisense Oligonucleotides
Modulators
Rats
Hippocampus
Transcription Factors
3'-(1-butylphosphoryl)adenosine
Degradation
IgA receptor

ASJC Scopus subject areas

  • Biochemistry

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Opposing roles for NF-κB/Rel factors p65 and c-Rel in the modulation of neuron survival elicited by glutamate and interleukin-1β. / Pizzi, Marina; Goffi, Francesca; Boroni, Flora; Benarese, Marina; Perkins, Scott E.; Liouand, Hsiou Chi; Spano, Pierfranco.

In: Journal of Biological Chemistry, Vol. 277, No. 23, 07.06.2002, p. 20717-20723.

Research output: Contribution to journalArticle

Pizzi, Marina ; Goffi, Francesca ; Boroni, Flora ; Benarese, Marina ; Perkins, Scott E. ; Liouand, Hsiou Chi ; Spano, Pierfranco. / Opposing roles for NF-κB/Rel factors p65 and c-Rel in the modulation of neuron survival elicited by glutamate and interleukin-1β. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 23. pp. 20717-20723.
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