Appearance of Nuclear-sorted Caspase-12 Fragments in Cerebral Cortical and Hippocampal Neurons in Rats Damaged by Autologous Blood Clot Embolic Brain Infarctions
Appearance of Nuclear-sorted Caspase-12 Fragments in Cerebral Cortical and Hippocampal Neurons in Rats Damaged by Autologous Blood Clot Embolic Brain Infarctions
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DOI：
10.1007/s10571-011-9687-0
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发表时间：
2011-04
影响因子：
4
通讯作者：
K. Shimoke;Yoshinori Matsuki;K. Fukunaga;Y. Matsumura;E. Fujita;Kensuke Sugihara;Masamichi Nobuhara;Hiroki Maruoka;T. Ikeuchi;Motoshige Kudo
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文献类型：
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作者：
K. Shimoke;Yoshinori Matsuki;K. Fukunaga;Y. Matsumura;E. Fujita;Kensuke Sugihara;Masamichi Nobuhara;Hiroki Maruoka;T. Ikeuchi;Motoshige Kudo
在内质网(ER)应激后，脑梗塞被报道涉及一个凋亡过程，包括caspase级联的激活。为了证实碎片化的caspase-12是否也参与了大鼠的栓塞性脑梗塞，我们采用了一种自体血液凝块模型来分析脑梗塞。我们在患有脑梗塞的大鼠身上进行了实验，脑梗塞与栓塞性脑梗塞密切相关。我们利用同种血块，即天然材料，形成梗死区。我们的发现表明，当大脑皮层神经元形成梗死区时，caspase-12是片段化的。有趣的是，我们观察到这些片段不仅转移到大脑皮层神经元的核中，而且转移到海马神经元的核中。我们进一步发现，作为内质网应激标志的葡萄糖调节蛋白78(GRP78)在脑梗塞期间在大脑皮层和海马神经元中表达上调。这一结果表明，caspase-12的断裂以及随后这些片段的核转位参与了大鼠脑梗塞的过程。
Following endoplasmic reticulum (ER) stress, cerebral infarctions have been reported to involve an apoptotic process, including the activation of the caspase cascade. To confirm whether fragmented caspase-12, which is activated by cleavage and is detectable during ER stress, is also involved in embolic cerebral infarctions in rats, we adopted an autologous blood clot model for the analysis of cerebral infarctions. We performed experiments in rats with brain infarctions, which are closely related to embolic cerebral infarctions. We utilized a homologous blood clot, i.e., natural materials, to form the infarct area. Our findings reveal that caspase-12 is fragmented when infarct areas form in cerebral cortical neurons. Interestingly, we observed that these fragments translocated to the nuclei of not only cerebral cortical neurons but hippocampal neurons. We further found that glucose-regulated protein 78 (GRP78), a marker of ER stress, is up-regulated in both cerebral cortical and hippocampal neurons during cerebral infarction. This result suggests that the fragmentation of caspase-12 and the subsequent nuclear translocation of these fragments are involved in the brain infarction process in rats.