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

Nuray Erin, Melvin Billingsley

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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 μM). 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.

Original languageEnglish (US)
Pages (from-to)45-52
Number of pages8
JournalBrain Research
Volume1014
Issue number1-2
DOIs
StatePublished - Jul 16 2004

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Inositol 1,4,5-Trisphosphate Receptors
Calcineurin
Brain
Ischemia
Neurons
Neurotoxins
Caspase 3
Proteins
domoic acid
Calcium
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

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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. / Erin, Nuray; Billingsley, Melvin.

In: Brain Research, Vol. 1014, No. 1-2, 16.07.2004, p. 45-52.

Research output: Contribution to journalArticle

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