RGD Reference Report - Opposing roles for NF-kappa B/Rel factors p65 and c-Rel in the modulation of neuron survival elicited by glutamate and interleukin-1beta. - Rat Genome Database

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Opposing roles for NF-kappa B/Rel factors p65 and c-Rel in the modulation of neuron survival elicited by glutamate and interleukin-1beta.

Authors: Pizzi, M  Goffi, F  Boroni, F  Benarese, M  Perkins, SE  Liou, HC  Spano, P 
Citation: Pizzi M, etal., J Biol Chem. 2002 Jun 7;277(23):20717-23. Epub 2002 Mar 23.
RGD ID: 2300288
Pubmed: PMID:11912207   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M201014200   (Journal Full-text)

The nuclear transcription factors NF-kappaB/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-kappaB/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-kappaB/Rel activation induced by two opposing modulators of cell viability: 1) interleukin-1beta (IL-1beta), which promotes neuron survival and 2) glutamate, which can elicit toxicity. IL-1beta produced a prolonged stimulation of NF-kappaB/Rel factors by inducing both IkappaBalpha and IkappaBbeta degradation. Glutamate produced a delayed and transient activation of NF-kappaB/Rel, which was associated with a brief loss of IkappaBalpha. Moreover, IL-1beta activated the p50, p65, and c-Rel subunits of NF-kappaB/Rel, whereas glutamate activated only the p50 and p65 proteins. The inhibition of NF-kappaB/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-1beta-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-1beta 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-kappaB/Rel proteins.



Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
RelRatcytoplasm  IDA MMO:0000538RGD 
RelaRatcytoplasm  IDA MMO:0000538RGD 
RelRatnucleus  IDA MMO:0000538RGD 
RelaRatnucleus  IDA MMO:0000538RGD 

Objects Annotated

Genes (Rattus norvegicus)
Rel  (REL proto-oncogene, NF-kB subunit)
Rela  (RELA proto-oncogene, NF-kB subunit)


Additional Information