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Objective:To explore the mechanism of endoplasmic reticulum stress(ERS)response and related apoptosis in dopaminergic neurons death.Methods:Nerve growth factor(NGF)-treatedPC12 cells were treated with 6-OHDA,MPP+ and rotenone.MTT assay and flow cytometry were used to measure the cell viability and the rate of celluar apoptosis induced by those neurotoxins.The expression of ERS-related gene XBP1,Grp78,CHOP,caspase-12 in drug-treated group and reserpine preincubation group was determined with RT-polymerase chain reaction(RT-PCR)and immunohistochemistry.Results:After the exposure to different toxins,the viability of PC12 cells were decreased by 52%,44%,40% at 100 μM6-OHDA,75 μM MPP+,20 nM rotenone for 24 h respectively.FCM assay confirmed time-dependent cell apoptosis(P < 0.01).The gene and protein expression of XBP1,Grp78 in drug-treated group were significantly increased and reached their peaks 8 h after the treatment(P < 0.05).The expression levels of CHOP and caspase-12 gene were increased 16-24 h after the treatment(P < 0.01),but the expression level of caspase-12 was inhibited by reserpine preincubayion(P < 0.05).Conclusion:The excessive ERS and relative activated cell apoptosis pathway may be associated with selective death of dopaminergic neurons.
Objective: To explore the mechanism of endoplasmic reticulum stress (ERS) response and related apoptosis in dopaminergic neurons death. Methods: Nerve growth factor (NGF) -treatedPC12 cells were treated with 6-OHDA, MPP + and rotenone. MTT assay and flow cytometry were used to measure the cell viability and the rate of celluar apoptosis induced by those neurotoxins. The expression of ERS-related gene XBP1, Grp78, CHOP, caspase-12 in drug-treated group and reserpine preincubation group was determined with RT-polymerase chain reaction Results: After the exposure to different toxins, the viability of PC12 cells were decreased by 52%, 44%, 40% at 100 μM 6-OHDA, 75 μM MPP +, 20 nM rotenone for 24 h respectively The gene and protein expression of XBP1, Grp78 in drug-treated group were significantly increased and reached their peaks after 8 h treatment (P <0.05) of CHOP and caspase-12 gene were in (P <0.01), but the expression level of caspase-12 was inhibited by reserpine preincubayion (P <0.05) .Conclusion: The excessive ERS and relative activated cell apoptosis pathway may be associated with selective death of dopaminergic neurons.