Caspase regulation of neuronal progenitor cell apoptosis
Caspase regulation of neuronal progenitor cell apoptosis
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DOI：
10.1159/000017433
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发表时间：
2000-01-01
影响因子：
2.9
通讯作者：
Roth, KA
中科院分区：
文献类型：
--
作者：
D'Sa-Eipper, C;Roth, KA
增殖的神经母细胞和有丝分裂后神经元的程序性细胞死亡（凋亡）对于正常的神经系统发育是必不可少的。为了研究神经元祖细胞凋亡的分子调控，我们开发了一种能够区分存活、凋亡和坏死细胞群的流式细胞术。将来自妊娠第12-13天小鼠胚胎的新鲜分离的端脑细胞与阿糖胞苷（AraC）或星形孢菌素一起孵育引起凋亡细胞百分比的显著增加。两种药物均诱导半胱天冬酶-3活化，如通过半胱天冬酶-3底物的体外切割和活化的半胱天冬酶-3的免疫细胞化学检测所确定的。用广泛的半胱天冬酶抑制剂BAF处理端脑细胞，阻断半胱天冬酶-3活化并保护细胞免受AraC和星形孢菌素诱导的凋亡性死亡。这些结果表明，神经元祖细胞具有半胱天冬酶依赖的凋亡途径，其激活可以调节体内神经元祖细胞的数量。版权所有（C）2000 S. Karger AG，巴塞尔。
Programmed cell death (apoptosis) of both proliferating neuroblasts and postmitotic neurons is essential for normal nervous system development. To study the molecular regulation of apoptosis in neuronal progenitor cells, we developed a flow cytometric assay capable of distinguishing between viable, apoptotic, and necrotic cell populations. Incubation of freshly dissociated telencephalic cells from gestational day 12-13 mouse embryos with either cytosine arabinoside (AraC) or staurosporine caused a marked increase in the percentage of apoptotic cells, Both drugs induced caspase-3 activation, as determined by in vitro cleavage of a caspase-3 substrate and immunocytochemical detection of activated caspase-3, Treatment of telencephalic cells with the broad caspase inhibitor BAF, blocked caspase-3 activation and protected cells against both AraC and staurosporine-induced apoptotic death. These results indicate that neuronal progenitors possess a caspase-dependent apoptotic pathway, the activation of which may regulate neuronal progenitor cell numbers in vivo. Copyright (C) 2000 S. Karger AG, Basel.