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The contribution of Cdc2 in rotenone-induced G2/M arrest and caspase-3-dependent apoptosis

Hongcai Wang1, Zhentao Zhang, Jinsha Huang

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

Journal of Molecular Neuroscience : MN
|December 17, 2013
PubMed

Insights

Parkinson's disease (PD) involves dopaminergic neuron death linked to cell cycle reentry. Cdc2 deregulation contributes to this cell death by enhancing G2/M arrest and caspase-3/9 dependent apoptosis.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • Neuronal cell cycle reentry in a G2-like state precedes cell death in Parkinson's disease (PD) dopaminergic neurons.
  • Caspase-3 is a key effector in the apoptosis of these neurons, but its link to aberrant G2/M regulation is unclear.
  • Cell division cycle protein 2 (Cdc2) regulates G2/M transition, and its deregulation is implicated in neuronal apoptosis, though the mechanism is not fully understood.

Purpose of the Study:

  • To investigate the role of Cdc2 deregulation in the G2/M arrest and caspase-3/9 dependent apoptosis of dopaminergic neurons in a rotenone-induced Parkinson's disease model.
  • To elucidate the molecular pathway connecting Cdc2 activity, cell cycle arrest, and apoptosis.

Main Methods:

  • Utilized a rotenone-based cell model to mimic Parkinson's disease.
  • Assessed cell cycle progression (G2/M phase), caspase-3 activation, and Cdc2 expression and activity.
  • Employed roscovitine and Cdc2 expression suppression to modulate cell cycle and apoptosis.

Main Results:

  • Rotenone induced G2/M cell cycle arrest and activated caspase-3 in both cytoplasmic and nuclear compartments.
  • Decreased Cdc2 activity (via roscovitine or rotenone) exacerbated G2/M arrest.
  • Rotenone treatment upregulated Cdc2 expression, leading to enhanced G2/M arrest.
  • Suppression of Cdc2 expression reduced cleaved caspase-3/9 levels and delayed apoptosis.

Conclusions:

  • Upregulation of Cdc2 is a key factor in rotenone-induced, caspase-3/9 dependent apoptosis in a Parkinson's disease model.
  • Cdc2 deregulation acts as a critical link between cell cycle arrest and cell death in this context.
  • These findings highlight Cdc2 as a potential therapeutic target for Parkinson's disease.

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