title: The contribution of Cdc2 in rotenone-induced G2/M arrest and caspase-3-dependent apoptosis.
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.
authors: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jie Fang Road, Wuhan, 430022, Hubei, China.
authors: Hongcai
authors: H
authors: Wang
authors: Zhentao
authors: Z
authors: Zhang
authors: Jinsha
authors: J
authors: Huang
authors: Ping
authors: P
authors: Zhang
authors: Nian
authors: N
authors: Xiong
authors: Tao
authors: T
authors: Wang
mesh_terms: D017209:Apoptosis; D016203:CDC2 Protein Kinase; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D059565:G2 Phase Cell Cycle Checkpoints; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D012402:Rotenone / Q000494:pharmacology*
chemical_list: D012402:Rotenone; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases; D053148:Caspase 3