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6-OHDA Induces Cycle Reentry and Apoetosis of PC12 Cells through Activation of ERK1/2 Signaling Pathway
Authors:Zhentao ZHANG  Tao WANG  Xuebing CAO  Shenggang SUN  Lan WANG
Affiliation:Department of Neurology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China
Abstract:This study investigated the effect and mechanism of cell cycle reentry induced by 6-hydrodopamine (6-OHDA) in PCI2 cells.By using neural differentiated PCI2 cells treated with 6-OHDA,the apoptosis model of dopaminergic neurons was established.Cell viability was measured by MTT.Cell apoptosis and the distribution of cell cycle were assessed by flow cytometry.Western blot was used to detect the activation of extracellular regulator kinasel/2 (ERK1/2) pathway and the phosphorylation of retinoblastoma protein (RB).Our results showed that after PC12 cells were treated wtih 6-OHDA,the viability of PC12 cells was declined in a concentration-dependent manner.Flow cytometry revealed that 6-OHDA could increase the apoptosis ratio of PC12 cells in a time-dependent manner.The percentage of cells in G0/G1 phase of cell cycle was decreased and that in S phase and G2/M phase increased.Simultaneously,ERK1/2 pathway was activated and phos- phorylated RB increased.It was concluded that 6-OHDA could induce cell cycle reentry of dopa-minergic neurons through the activation of ERK1/2 pathway and RB phosphorylation.The aberrant cell cycle reentry contributes to the apoptosis of dopaminergic neurons.
Keywords:6-hydrodopamine  cell cycle  extracellular regulator kinase1/2  retinoblastoma protein  Parkinson' s disease
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