Caspase-dependent programmed cell death pathways are not activated in generalized seizure-induced neuronal death
Caspase-dependent programmed cell death pathways are not activated in generalized seizure-induced neuronal death
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DOI：
10.1016/j.brainres.2006.12.029
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发表时间：
2007-03-02
期刊：
影响因子：
2.9
通讯作者：
Aviles, Ernesto R., Jr.
中科院分区：
文献类型：
--
作者：
Fujikawa, Denson G.;Shinmei, Steve S.;Aviles, Ernesto R., Jr.
半胱天冬酶依赖性细胞死亡途径的激活已被证明在局灶性癫痫发作，但这是否发生在长期的全面性癫痫发作是未知的。我们研究了在锂-匹鲁卡品诱导的癫痫持续状态后的第一个24小时内，当神经元死亡最大且广泛时，是否激活了外源性途径中的启动剂caspase-8或内源性途径caspase-9。给予甲基苯丙胺的大鼠胸腺被用作caspase-3激活的细胞凋亡的阳性对照。甲基苯丙胺处理后，caspase-9，但不是caspase-8被激活的胸腺细胞。然而，6或24小时后癫痫持续状态，没有26个脑区的研究显示，无论是caspase-8或-9激活免疫组化，蛋白质印迹和酶活性测定。我们的研究结果提供了证据，对激活的外在和内在的caspase途径在全面性癫痫发作，产生形态坏死的神经元与核小体间DNA裂解（DNA梯状），程序化的过程。相反，有越来越多的证据表明，半胱天冬酶独立的程序化机制发挥了突出的作用，在脑缺血诱导的神经元死亡。由爱思唯尔公司出版
Activation of the caspase-dependent cell death pathways has been shown in focal seizures, but whether this occurs in prolonged generalized seizures is not known. We investigated whether the initiator caspase in the extrinsic pathway, caspase-8, or the intrinsic pathway, caspase-9, is activated during the first 24 h following lithium-pilocarpine-induced status epilepticus, when neuronal death is maximal and widespread. The thymuses of rats given methamphetamine were used as positive controls for caspase-3-activated cellular apoptosis. Following methamphetamine treatment, caspase-9 but not caspase-8 was activated in thymocytes. However, 6 or 24 h following status epilepticus, none of 26 brain regions studied showed either caspase-8 or -9 activation by immunohistochemistry, western blotting and enzyme activity assays. Our results provide evidence against the activation of the extrinsic and intrinsic caspase pathways in generalized seizures, which produce morphologically necrotic neurons with internucleosomal DNA cleavage (DNA laddering), a programmed process. In contrast, there is increasing evidence that caspase-independent programmed mechanisms play a prominent role in seizure-induced neuronal death. Published by Elsevier B.V.