Post-ischemic activation of caspase-3 in the rat hippocampus: evidence of an axonal and dendritic localisation
Post-ischemic activation of caspase-3 in the rat hippocampus: evidence of an axonal and dendritic localisation
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DOI：
10.1016/s0197-0186(03)00002-0
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发表时间：
2003-08-01
影响因子：
4.2
通讯作者：
Winckler, J
中科院分区：
文献类型：
--
作者：
Rami, A;Jansen, S;Winckler, J
检测缺血后caspase-3激活与迟发性神经元死亡之间的关系。通过比色分析、免疫印迹和免疫组织化学方法评估caspase-3的表达。细胞凋亡的特点是末端脱氧核苷酸转移酶介导的尿苷5 '-三磷酸-生物素缺口末端标记。免疫组化显示，caspase-3激活在整个海马早在30分钟后，缺血与独家定位在纤维系统，特别是在穿通路径和苔藓纤维，谢弗侧支，以及顶端和基底树突的锥体细胞。缺血后1天，在整个亚区的所有细胞隔室（细胞核、胞质溶胶和树突）和齿状回中观察到caspase-3（p18）的18 kDa裂解产物，并在苔藓纤维中高度分布。缺血后2天，p18 kDa仅见于海马细胞核和胞浆中，海马各亚区之间无特异性区域差异。缺血后2-3天，仅在海马CA 1区锥体细胞出现大量凋亡细胞。我们的数据提供了第一个证据表明，caspase-3的激活是可检测到的三突触通路纤维束，可能对应于穿通路径，阿尔韦亚路径和Schaffer的侧枝，caspase-3的激活导致执行的凋亡细胞死亡程序在选择性脆弱的区域，而不是在海马的抵抗区。(C)2003爱思唯尔科技有限公司版权所有。
The relationship between caspase-3 activation and delayed neuronal death after ischemia was examined. Expression of caspase-3 was evaluated by colorimetric assay, immunoblotting and by immunohistochemistry. Apoptosis was characterised by terminal desoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labelling. Immunohistochemistry showed caspase-3 activation in the whole hippocampus as early as 30 min after ischemia with exclusive localisation in fiber systems, especially in the perforant path and mossy fibers, Schaffer-collaterals, as well as apical and basal dendrites of pyramidal cells. One day post-ischemia, the 18 kDa cleavage product of caspase-3 (p18) was seen in all cell compartments (nucleus, cytosol and dendrites) throughout the entire subfields and the dentate gyrus with high distribution in mossy fibers. Two days post-ischemia, p18 kDa was only seen in the nuclei and cytosol of hippocampal cells without specific regional differences among hippocampal subfields. A significant number of apoptotic cells appeared only in the CA1 pyramidal cells at 2-3 days post-ischemia. Our data provides the first evidence that caspase-3 activation was detectable in the trisynaptic pathway fiber bundles which probably correspond to perforant path, alvear path and collaterals of Schaffer, and that activation of caspase-3 led to execution of apoptotic cell death program in selectively vulnerable areas, but not in the resistant area of the hippocampus. (C) 2003 Elsevier Science Ltd. All rights reserved.