The Effect and Mechanism of Dopaminergic Cell Cycle Reentry Induced by MPP

Objective To investigate the effect and mechanism of dopaminergic cell cycle reentry induced by MPP~(+).Methods PC12 cells as dopaminergic neurons,differentiated by nerve growth factor,were treated by MPP~(+).Cell viability was measured by MTT,flow cytometry was used to detect cell apoptosis and the changes of cell cycle,and immunocytochemistry was used to study the activation state of ERK1/2 pathway.Results After treated with MPP~(+) the cell viability declined in a concentration-dependent manner.Compared with the control group,exposing to 25,50,75,100 and 150 mmol/L MPP~(+) for 24 h caused cell viability decline to(7.32±2.41)%,(7.69±3.03)%,(56.00±3.12)%,(47.23±2.55)% and(40.00±2.46)%(P0.01)respectively.The early sign of apoptosis was found with flow cytometry,and the apoptosis ratio increased in a time-dependent manner.The apoptosis ratios induced by 75 mmol/L MPP~(+) for 4,8,16 and 24 h were(7.26±3.43)%,(8.34±3.55)%,(20.04±2.64)% and(28.46±2.35)%(P0.01)respectively.The percentage of cells in the G0/G1 phase decreased and that in the G2/M phase increased(P0.01).This was associated with a rapid activation of phosphorylated ERK1/2.Conclusions MPP~(+) might induce cell apoptosis of dopaminergic neuron by activation of ERK1/2 pathway and the subsequently reentry of cell cycle.