Prolonged translation arrest in reperfused hippocampal cornu ammonis 1 is mediated by stress granules
Prolonged translation arrest in reperfused hippocampal cornu ammonis 1 is mediated by stress granules
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DOI：
10.1016/j.neuroscience.2005.05.047
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发表时间：
2005-01-01
期刊：
影响因子：
3.3
通讯作者：
DeGracia, DJ
中科院分区：
文献类型：
--
作者：
Kayali, F;Montie, HL;DeGracia, DJ
全脑缺血和再灌注导致真核细胞起始因子2 α的α亚基磷酸化，这是一种与神经元翻译抑制相关的可逆事件。然而，氨角（CA）1锥体神经元的选择性脆弱性与不可逆的翻译抑制相关。真核起始因子2 α的磷酸化还导致应激颗粒、部分含有48S前起始复合物和RNA结合蛋白T细胞内部抗原-1（TIA-1）的组分的细胞质病灶的形成。应激颗粒是机体非激活性蛋白质合成的场所。在这里，我们评估了应激颗粒在大鼠海马结构神经元后10分钟的全脑缺血和10分钟，90分钟或4小时的再灌注双标记免疫荧光的两个应激颗粒组分：小核糖体亚基蛋白6和TIA-1。再灌注10 min时，CA3、门和齿状回的应激颗粒增多，90 min时恢复到对照组水平。TIA-1的核分布的动态变化发生在抗性神经元。在4小时再灌注，核糖体小亚基蛋白6只局限于应激颗粒内仅在CA 1锥体神经元。TIA-1和小核糖体亚基蛋白6水平在海马匀浆中下降了50%。电镜观察显示，应激颗粒由直径100 - 200 nm的电子致密体组成，这些电子致密体不与膜结合，但与内质网结合。CA1锥体神经元中应激颗粒行为的改变为真核起始因子2 α去磷酸化后再灌注CA1锥体神经元中蛋白质合成的持续抑制提供了明确的机制。(c)2005年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Global brain ischemia and reperfusion cause phosphorylation of the alpha subunit of eukaryotic initiation factor 2 alpha, a reversible event associated with neuronal translation inhibition. However, the selective vulnerability of cornu Ammonis (CA) 1 pyramidal neurons correlates with irreversible translation inhibition. Phosphorylation of eukaryotic initiation factor 2 alpha also leads to the formation of stress granules, cytoplasmic foci containing, in part, components of the 48S pre-initiation complex and the RNA binding protein T cell internal antigen-1 (TIA-1). Stress granules are sites of translationally inactive protein synthesis machinery. Here we evaluated stress granules in rat hippocampal formation neurons after 10 min global brain ischemia and 10 min, 90 min or 4 h of reperfusion by double-labeling immunofluorescence for two stress granule components: small ribosomal subunit protein 6 and TIA-1. Stress granules in CA3, hilus and dentate gyrus, but not CA1, increased at 10 min reperfusion and returned to control levels by 90 min reperfusion. Dynamic changes in the nuclear distribution of TIA-1 occurred in resistant neurons. At 4 h reperfusion, small ribosomal subunit protein 6 was solely localized within stress granules only in CA1 pyramidal neurons. Both TIA-1 and small ribosomal subunit protein 6 levels decreased similar to 50% in hippocampus homogenates. Electron microscopy showed stress granules to be composed of electron dense bodies 100-200 nm in diameter, that were not membrane bound, but were associated with endoplasmic reticulum. Alterations in stress granule behavior in CA1 pyramidal neurons provide a definitive mechanism for the continued inhibition of protein synthesis in reperfused CA1 pyramidal neurons following dephosphorylation of eukaryotic initiation factor 2 alpha. (c) 2005 IBRO. Published by Elsevier Ltd. All rights reserved.