Domoic acid enhances Bcl-2-calcineurin-inositol-1,4,5-trisphosphate receptor interactions and delayed neuronal death in rat brain slices
Domoic acid enhances Bcl-2-calcineurin-inositol-1,4,5-trisphosphate receptor interactions and delayed neuronal death in rat brain slices
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DOI：
10.1016/j.brainres.2004.03.076
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发表时间：
2004-07-16
期刊：
影响因子：
2.9
通讯作者：
Billingsley, ML
中科院分区：
文献类型：
--
作者：
Erin, N;Billingsley, ML
软骨藻酸致神经元损伤后神经元死亡的机制尚未完全确定。BCL-2是一种存活蛋白，可保护神经元免受缺血和兴奋性毒素的损伤。我们先前证明，在神经元缺血期间，Bcl2将钙调神经磷酸酶穿梭到其底物上，并可能调节内库的钙释放。我们现在证实，在软骨藻酸诱导的兴奋毒性过程中，钙调神经磷酸酶-Bcl-2和钙调神经磷酸酶-1，4，5-肌醇-三磷酸受体(IP3-R)的相互作用增加。此外，我们现在表明，在软骨藻酸(10微米)短期治疗后，脑片中钙调神经磷酸酶-IP3-R的相互作用是由Bcl-2介导的。软骨藻酸诱导器官型皮质和海马神经元晚期死亡和caspase-3样活性。这些实验进一步确定了神经元对兴奋性毒性损伤的反应机制，并表明钙调神经磷酸酶与其目标蛋白之间的相互作用可能会影响细胞对损伤的反应。(C)2004爱思唯尔B.V.保留所有权利。
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 muM). 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. (C) 2004 Elsevier B.V. All rights reserved.