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The Contribution of Cdc2 in Rotenone-Induced G2/M Arrest and Caspase-3-Dependent Apoptosis

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An Erratum to this article was published on 04 February 2014

Abstract

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.

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Acknowledgments

This work was supported by grants (No. 81071021 and No. 31171211) from the National Natural Science Foundation of China (to Tao Wang), grant (No. 81100958) from the National Natural Science Foundation of China (to Zhentao Zhang), grant (No. 81200983) from the National Natural Science Foundation of China (to Nian Xiong), grant (No. 2012B09) from the China Medical Foundation (to Nian Xiong).

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The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jie Fang Road, Wuhan, 430022, Hubei, China

    Hongcai Wang, Jinsha Huang, Ping Zhang, Nian Xiong & Tao Wang

  2. Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, 430060, China

    Zhentao Zhang

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  1. Hongcai Wang
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  2. Zhentao Zhang
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  3. Jinsha Huang
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  4. Ping Zhang
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  5. Nian Xiong
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  6. Tao Wang
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Corresponding author

Correspondence to Tao Wang.

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Hongcai Wang and Zhentao Zhang contributed equally to this work.

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Wang, H., Zhang, Z., Huang, J. et al. The Contribution of Cdc2 in Rotenone-Induced G2/M Arrest and Caspase-3-Dependent Apoptosis. J Mol Neurosci 53, 31–40 (2014). https://doi.org/10.1007/s12031-013-0185-3

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  • DOI: https://doi.org/10.1007/s12031-013-0185-3

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