Opposing Roles for NF-κB/Rel Factors p65 and c-Rel in the Modulation of Neuron Survival Elicited by Glutamate and Interleukin-1β*

By M. Pizzi, F. Goffi, F. Boroni, M. Benarese, Scott Perkins, H. Liou, P. Spano. Journal of Biological Chemistry, 2002

150 citations recorded by the source corpus.

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.

Subfields: Cancer Research, Immunology

View Paper: https://www.semanticscholar.org/paper/500cbc072a7a99afa97d1f85c21d16c7437b1a6b

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Citations in the corpus

• To be, or not to be: NF-κB is the answer – role of Rel/NF-κB in the regulation of apoptosis (2003, background): “Whereas glutamate activated p50/NF-kB1 and p65/ RelA in cultured rat cerebellar granule cells and mouse hippocampal slices, treatment with IL-1b that promotes neuron survival activated expression of c-Rel along with p50/NF-kB1 and p65/RelA (Pizzi et al., 2002).”