Regulation of X-chromosome-linked inhibitor of apoptosis protein in kainic acid-induced neuronal death in the rat hippocampus
Regulation of X-chromosome-linked inhibitor of apoptosis protein in kainic acid-induced neuronal death in the rat hippocampus
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DOI：
10.1006/mcne.2000.0935
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发表时间：
2001-02-01
影响因子：
3.5
通讯作者：
Lindholm, D
中科院分区：
文献类型：
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作者：
Korhonen, L;Belluardo, N;Lindholm, D
XIAP（X染色体相关凋亡抑制蛋白）是一种抗凋亡蛋白，可抑制半胱氨酸蛋白酶的活性并抑制细胞死亡。然而，XIAP在神经系统中的存在和功能知之甚少。在这里，我们报告，XIAP mRNA表达在发育和成年大鼠脑。使用特异性抗体，我们观察到XIAP免疫反应细胞在不同的大脑区域，其中包括在海马和大脑皮层。海人酸可诱导特定神经元的延迟性细胞死亡，增加海马CA 3区的XIAP水平。然而，XIAP在经历细胞死亡的细胞中基本上不存在，如通过TUNEL标记和活性半胱天冬酶-3染色所示。在培养的海马神经元中，XIAP最初被红藻氨酸上调，然后在caspase-3抑制剂DEVD阻断的过程中降解。类似地，重组XIAP在体外被活性半胱天冬酶-3切割。结果表明，红藻氨酸后，海马中XIAP存在双相调节，并且XIAP成为海马中细胞死亡期间激活的caspase-3的靶标。海人酸降解XIAP导致caspase激活后在海马脆弱神经元中观察到的神经元细胞死亡。
XIAP (X-chromosome-linked inhibitor of apoptosis protein) is an antiapoptotic protein which inhibits the activity of caspases and suppresses cell death. However, little is known about the presence and function of XIAP in the nervous system. Here we report that XIAP mRNA is expressed in developing and adult rat brain. Using a specific antibody, we observed XIAP-immunoreactive cells in different brain regions, among others, in the hippocampus and cerebral cortex. Kainic acid, which induces delayed cell death of specific neurons, increased the levels of XIAP in the CA3 region of hippocampus. XIAP was, however, largely absent in cells undergoing cell death, as shown by TUNEL labeling and staining for active caspase-3. In cultured hippocampal neurons, XIAP was initially upregulated by kainic acid and then degraded in a process blocked by the caspase-3 inhibitor DEVD. Similarly, recombinant XIAP is cleaved by active caspase-3 in vitro. The results show that there is biphasic regulation of XIAP in the hippocampus following kainic acid and that XIAP becomes a target for caspase-3 activated during cell death in the hippocampus. The degradation of XIAP by kainic acid contributes to neuronal cell death observed in vulnerable neurons of the hippocampus after caspase activation.