RGD Reference Report - Domoic acid enhances Bcl-2-calcineurin-inositol-1,4,5-trisphosphate receptor interactions and delayed neuronal death in rat brain slices. - Rat Genome Database

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Domoic acid enhances Bcl-2-calcineurin-inositol-1,4,5-trisphosphate receptor interactions and delayed neuronal death in rat brain slices.

Authors: Erin, N  Billingsley, ML 
Citation: Erin N and Billingsley ML, Brain Res. 2004 Jul 16;1014(1-2):45-52.
RGD ID: 6482804
Pubmed: PMID:15212990   (View Abstract at PubMed)
DOI: DOI:10.1016/j.brainres.2004.03.076   (Journal Full-text)

Mechanisms of neuronal death following neuronal damage due to domoic acid are not completely defined. Bcl-2, a survival protein, protects neurons from ischemia and excitotoxin-induced damage. We previously demonstrated that Bcl-2 shuttles calcineurin to its substrates and may regulate calcium release from internal stores during neuronal ischemia. We now confirm that during excitotoxicity induced by domoic acid, calcineurin-Bcl-2 and calcineurin-1,4,5-inositol-trisphosphate receptor (IP3-R) interactions increase. Furthermore, we now show that calcineurin-IP3-R interactions are mediated by Bcl-2 in brain slices following short-term treatment with domoic acid (10 microM). Domoic acid induced late neuronal death and caspase-3-like activity in organotypic cortical and hippocampal cultures. These experiments further define the mechanisms by which neurons respond to excitotoxic insults, and suggest that interactions between calcineurin and its target proteins may influence cellular responses to injury.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein phosphatase binding  IDA 6482804calcineurinRGD 
protein-containing complex binding  IDA 6482804Bcl-2 and calcineurinRGD 

Objects Annotated

Genes (Rattus norvegicus)
Itpr1  (inositol 1,4,5-trisphosphate receptor, type 1)


Additional Information