Comparative study of endoplasmic reticulum stress-induced neuronal death in rat cultured hippocampal and cerebellar granule neurons
Comparative study of endoplasmic reticulum stress-induced neuronal death in rat cultured hippocampal and cerebellar granule neurons
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DOI：
10.1016/j.neuint.2006.01.021
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发表时间：
2006-08-01
影响因子：
4.2
通讯作者：
Ito, Yoshihisa
中科院分区：
文献类型：
--
作者：
Kosuge, Yasuhiro;Sakikubo, Taeko;Ito, Yoshihisa
在这项研究中，进行实验，以进一步表征负责内质网（ER）应激诱导的神经元死亡的途径在培养的海马神经元（HPN）和小脑颗粒神经元（CGN）使用衣霉素（TM）和淀粉样β-肽（A β）。HPN暴露于A β或TM导致78-kDa葡萄糖调节蛋白（GRP 78）和caspase-12（一种ER驻留的caspase）表达的时间依赖性增加。与此相反，在CGN中，尽管发现GRP 78的表达急剧增加，如在HPN中的情况，但没有检测到caspase-12的上调。这些结果与免疫组化结果一致，即小脑中caspase-12阳性细胞的数量远低于大脑皮层和海马，并且在P7大鼠小脑的外部颗粒细胞层中未发现caspase-12阳性细胞。在CGN中，暴露于A β或TM后检测到C/EBP同源蛋白（CHOP）蛋白表达的显著增加，而在HPN中未观察到蛋白表达的增加。此外，S-烯丙基-L-半胱氨酸（SAC），一种从老化大蒜提取物中纯化的有机硫化合物，在HPN中保护神经元免受TM诱导的神经毒性，但在CGN中不保护神经元，如在A β诱导的神经毒性的情况下。这些结果表明，在HPN中负责由A β和TM诱导的神经元死亡的途径与CGN中的途径不同，并且在ER应激诱导的神经元死亡中，HPN中涉及caspase-12依赖性途径，而CGN中涉及CHOP依赖性途径。(c)2006爱思唯尔有限公司保留所有权利。
In this study, experiments were performed to characterize further the pathways responsible for neuronal death induced by endoplasmic reticulum (ER) stress in cultured hippocampal neurons (HPN) and cerebellar granule neurons (CGN) using tunicamycin (TM) and amyloid beta-peptide (A beta). Exposure of HPN to A beta or TM resulted in a time-dependent increase in the expression of 78-kDa glucose-regulated protein (GRP78) and caspase-12, an ER-resident caspase. In contrast, in CGN, although a drastic increase in the expression of GRP78 was found as was the case in HPN, no up-regulation of caspase-12 was detected. These results were consistent with immunohistochemical results that there were far lower number of caspase-12-positive cells in the cerebellum than in the cerebral cortex and hippocampus, and that caspase-12-positive cells were not identified in the external granule cell layer of the cerebellum of P7 rats. In CGN, a significant increase in the expression of C/EBP homologous protein (CHOP) protein was detected after exposure to A beta or TM, whereas no such an increase in the protein expression was observed in HPN. In addition, S-allyl-L-Cysteine (SAC), an organosulfur compound purified from aged garlic extract, protected neurons against TM-induced neurotoxicity in HPN but not in CGN, as in the case of A beta-induced neurotoxicity. These results suggest that the pathway responsible for neuronal death induced by A beta and TM in HPN differs from that in CGN, and that a caspase-12-dependent pathway is involved in HPN while a CHOP-dependent pathway is involved in CGN in ER stress-induced neuronal death. (c) 2006 Elsevier Ltd. All rights reserved.