The Contribution of Cdc2 in Rotenone-Induced G2/M Arrest and Caspase-3-Dependent Apoptosis
The Contribution of Cdc2 in Rotenone-Induced G2/M Arrest and Caspase-3-Dependent Apoptosis
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DOI：
10.1007/s12031-013-0185-3
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发表时间：
2013-12
影响因子：
3.1
通讯作者：
Hongcai Wang;Zhentao Zhang;Jinsha Huang;Ping Zhang;N. Xiong;Tao Wang
中科院分区：
文献类型：
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作者：
Hongcai Wang;Zhentao Zhang;Jinsha Huang;Ping Zhang;N. Xiong;Tao Wang
在帕金森病(PD)患者的多巴胺能神经元中，已证实在细胞死亡前神经元周期重入维持在类G2状态。Caspase-3是患者多巴胺能神经元凋亡的最终效应因子。G2/M调控异常与caspase-3依赖的细胞凋亡之间的关系尚不清楚。细胞分裂周期蛋白2(CDC2)在有丝分裂细胞的G2/M转换中起关键作用。虽然CDc2的失控与神经细胞的凋亡控制有关，但其参与细胞凋亡的分子途径尚不清楚。在以鱼藤酮为基础的PD细胞模型中，我们发现鱼藤酮使细胞周期停滞在G2/M期，并激活了胞浆和胞核中的caspase-3。罗索维汀或鱼藤酮降低细胞内CDc2的活性，可使细胞发生G2/M期阻滞。鱼藤酮使细胞发生G2/M期阻滞，上调了CDc2的表达。抑制cdc2的表达下调了caspase-3/9的裂解，延缓了细胞的凋亡。综上所述，CDc2的上调有助于鱼藤酮诱导的caspase-3/9依赖的细胞凋亡，这与增强G2/M期的停滞有关。我们的结果表明，CDC2的解除调控是细胞周期停滞和细胞死亡之间的过渡。
Neuronal cell cycle reentry maintained in a G2-like state before cell death, has been confirmed in dopaminergic neurons of patients with Parkinson's disease (PD). Caspase-3 is a final effector in apoptotic dopaminergic neurons in patients. The association of aberrant G2/M regulation with caspase-3 dependent apoptosis remains to be elucidated. Cell division cycle protein 2 (Cdc2) is a key player in G2/M transition in mitotic cells. Although the deregulation of Cdc2 correlated with the control of apoptosis in neurons, the molecular pathway by which Cdc2 involves in apoptosis is not clear. In a rotenone-based cell model of PD, we demonstrated that rotenone arrested cell cycle at G2/M phase and activated caspase-3 both in cytoplasm and nucleus. The decreased activity of Cdc2 by roscovitine or rotenone enhanced G2/M arrest. The increased cells in G2/M arrest by rotenone upregulated the expression of Cdc2. Suppression of Cdc2 expression downregulated cleaved caspase-3/9 and delayed cell apoptosis. Used together, the upregulation of Cdc2 contributes to rotenone-induced caspase-3/9-dependent apoptosis, which is associated with the enhancement of G2/M arrest. Our results suggest the deregulation of Cdc2 as a transition between cell cycle arrest and cell death.