Differential DNases are selectively used in neuronal apoptosis depending on the differentiation state
Differential DNases are selectively used in neuronal apoptosis depending on the differentiation state
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DOI：
10.1038/sj.cdd.4401454
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发表时间：
2004-10-01
影响因子：
12.4
通讯作者：
Tanuma, S
中科院分区：
文献类型：
--
作者：
Shiokawa, D;Tanuma, S
在这项研究中，我们研究了两个凋亡核酸内切酶，CAD和DNase γ，在神经细胞凋亡的作用。CAD的高表达，但不是DNase γ，在增殖的N1 E-115神经母细胞瘤细胞中检测到，并且在增殖条件下由星形孢菌素诱导的凋亡DNA片段化被ICAD的半胱天冬酶抗性形式的表达所消除。在诱导神经元分化后，CAD消失和DNase γ的诱导在N1 E-115细胞中同时发生。在分化条件下发生的凋亡DNA片段化被其反义RNA引起的DNase γ的下调所抑制。在PC 12细胞的神经元分化过程中也观察到DNase γ的诱导，并且通过DNase γ的反义介导的下调来抑制由NGF剥夺诱导的凋亡DNA片段化。这些观察结果表明，神经元凋亡中的DNA片段化是由CAD或DNase γ催化的，这取决于分化状态。此外，DNase c被认为参与发育中的神经系统中自然发生的细胞凋亡。
In this study, we investigate the roles of two apoptotic endonucleases, CAD and DNase gamma, in neuronal apoptosis. High expression of CAD, but not DNase gamma, is detected in proliferating N1E-115 neuroblastoma cells, and apoptotic DNA fragmentation induced by staurosporine under proliferating conditions is abolished by the expression of a caspase-resistant form of ICAD. After the induction of neuronal differentiation, CAD disappearance and the induction of DNase gamma occur simultaneously in N1E-115 cells. Apoptotic DNA fragmentation that occurs under differentiating conditions is suppressed by the downregulation of DNase gamma caused by its antisense RNA. The induction of DNase gamma is also observed during neuronal differentiation of PC12 cells, and apoptotic DNA fragmentation induced by NGF deprivation is inhibited by the antisense-mediated downregulation of DNase gamma. These observations suggest that DNA fragmentation in neuronal apoptosis is catalyzed by either CAD or DNase gamma depending on the differentiation state. Furthermore, DNase c is suggested to be involved in naturally occurring apoptosis in developing nervous systems.