Ischemia-induced neuronal cell death is mediated by the endoplasmic reticulum stress pathway involving CHOP
Ischemia-induced neuronal cell death is mediated by the endoplasmic reticulum stress pathway involving CHOP
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DOI：
10.1038/sj.cdd.4401365
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发表时间：
2004-04-01
影响因子：
12.4
通讯作者：
Mori, M
中科院分区：
文献类型：
--
作者：
Tajiri, S;Oyadomari, S;Mori, M
脑缺血诱导神经细胞凋亡，但其机制尚不清楚。当野生型小鼠进行双侧颈总动脉闭塞（BCCAO）为15分钟，闭塞后48小时，在纹状体和海马中观察到凋亡相关的形态学变化和TUNEL阳性细胞的外观。RT-PCR分析显示，ER应激相关的促凋亡因子CHOP和ER伴侣BiP的mRNA在BCCAO后12小时显著诱导。免疫组织化学分析显示，在24小时后，受损神经元的细胞核中诱导CHOP蛋白。与此相反，缺血相关的神经元凋亡损失减少CHOP-/-小鼠。CHOP-/-小鼠的原代海马神经元比野生型动物对缺氧-复氧诱导的凋亡更具抵抗力。这些结果表明，缺血诱导的神经元细胞死亡是由ER应激途径介导的，涉及CHOP诱导。
Brain ischemia induces apoptosis in neuronal cells, but the mechanism is not well understood. When wild-type mice were subjected to bilateral common carotid arteries occlusion (BCCAO) for 15 min, apoptosis-associated morphological changes and appearance of TUNEL-positive cells were observed in the striatum and in the hippocampus at 48 h after occlusion. RT-PCR analysis revealed that mRNAs for ER stress-associated proapoptotic factor CHOP and an ER chaperone BiP are markedly induced at 12 h after BCCAO. Immunohistochemical analysis showed that CHOP protein is induced in nuclei of damaged neurons at 24 h after occlusion. In contrast, ischemia-associated apoptotic loss of neurons was decreased in CHOP-/- mice. Primary hippocampal neurons from CHOP-/- mice were more resistant to hypoxia-reoxygenation-induced apoptosis than those from wild-type animals. These results indicate that ischemia-induced neuronal cell death is mediated by the ER stress pathway involving CHOP induction.