The Double Effects of Proteasome Inhibitor on Neuron

Objective: To explore the effects of proteasome inhibitor on dopaminergic neuron at different concentration and its possible underlying reason. Methods: SH-SY5Y cells treated with 50uM 6-OHDA were used as a toxin insulted cell model. Proteasome inhibitor lactacystin were added to the medium simultaneously at different concentrations. Cell count and SRB was used to assess cell viability. The parallel groups were used to perform proteasome activity assay. PD98059,a specific MEK1/2 inhibitor,were used to demonstrate whether or not proteasome inhibitor protects dopaminergic neuron through MAPK pathway. Results: Cell viability increased when the concentration of proteasome inhibitor were 0.1,0.25,0.5uM with the proteasome activity 83 %,75 %,64 %respectively,While cell viability decreased when the concentration of proteasome inhibitor were2,5uM with the proteasome activity24.12 %,12.6 % respectively. When PD98059 were administrated the protective effect of proteasome inhibitor was blocked. Conclusion: Proteasome inhibitor protects dopaminergic neuron at a relatively low concentration,and it is toxic to dopaminergic neuron at a relatively high concentration. The double effects of proteasome inhibitor may be related to the degree of proteasome inhibition. proteasome inhibitor protect dopaminergic neuron through MAPK pathway.