Effects Of Thiamine Mediated Akt/m TOR/STAT3Signaling Pathway On PC12Cells Injury Induced By Glutamate

Objective Akt/mTOR/STAT3signaling pathway is considered as a central controller of the cell growth and metabolism,which plays an important role in regulation of the cell proliferation differentiation and apoptosis. Although there are dozens of studies on promote cell proliferation or suppress cell proliferation through the Akt/mTOR/STAT3signaling pathway,the particular effect and mechanism of the Akt/mTOR/STAT3signaling pathway in neuron injuries is still indefinite.This study was designed to investigate the effect of thiamine mediated Akt/mTOR/STAT3signaling pathway on PC12cells injury induced by glutamate.Methods The inhibition rates of PC12cells induced by different concentrations and treatment time of glutamate was observed using MTT assay, and then a proper concentration and treatment time were chosen to make the cell injury model.Then,PC12cells were assigned to group A (normal group), group B(20mmol/L glutamate),group C(20mmol/L glutamate+300μmol/L thiamine) and group D(20mmol/L glutamate+300μmol/L thiamine+800nmol/L rapamycin). The apoptosis of PC12cells was detected by flow cytometry in each group after12hours treatment. The expressions of p-Akt,p-mTOR and p-STAT3wers detected by western blot in each group after1hour,4hours,8hours and12hours treatment.Results (1) The inhibition rates of PC12cells was risen with the increase of concentration and treatment time of glutamate.(2) The apoptosis rate of group A was (3.42±0.79)%; Compared with group B [(40.20±2.54)%] and D [(53.49±2.83)%].the apoptosis rate of group C [(23.85±1.58)%] was decreased significantly<P<0.01).(3)Compared with group A.B and D.the expressions of p-Akt.p-mTOR and p-STAT3of group C were increased significantly at each time point(p<0.01).The expression of p-Akt reached the maximum at1hour.The expressions of p-mTOR and p-STAT3reached the peak at4hours after treatment.Conclusion Thiamine play a protective role in PC12cells injury induced by glutamate through reduce the PC12cells apoptosis,and this protective role may related to the activation of the Akt/mTOR/STAT3signaling pathway.