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

Erin N., Billingsley M. L.

Brain Research, cilt.1014, sa.1-2, ss.45-52, 2004 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 1014 Sayı: 1-2
  • Basım Tarihi: 2004
  • Doi Numarası: 10.1016/j.brainres.2004.03.076
  • Dergi Adı: Brain Research
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.45-52
  • Anahtar Kelimeler: 1,4,5-Inositol-trisphosphate receptor (IP3-R), Bcl-2, Calcineurin, Calcium, Disorders of the nervous system, Domoic acid, Neurotoxicity
  • Akdeniz Üniversitesi Adresli: Evet

Özet

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. © 2004 Elsevier B.V. All rights reserved.