蛋白酶体在乙醇诱发神经细胞毒性中的作用

目的探讨蛋白酶体在乙醇对神经细胞产生毒性中的作用。方法分别用50、10、150、200mmol／L的乙醇对PC12细胞进行48h染毒后，用四甲基偶氮唑盐微量酶反应比色(MTT)法检测乙醇对PC12细胞的细胞毒性，用荧光底物法测定细胞蛋白酶体的活力，并与对照组比较。结果100mmol／L以上浓度的乙醇染毒48h对PC12细胞产生明显的毒性作用，且呈现良好的剂量-反应关系；蛋白酶体活力的测定表明，乙醇显著抑制蛋白酶体的活力，有剂量和时间依赖关系。结论乙醇可能通过抑制蛋白酶体的活力，干扰了某些蛋白质的正常代谢，从而产生了细胞毒性。

Role of Proteasome Peptidase Activities in the Ethanol-Induced Cytotoxicity on PC12 Cells

Objective To clarify whether ethanol induced cytotoxicity of neurons was inhibited by proteasome peptidase activities. Methods A rat pheochromocytoma(PC12) was used in the present study. Cytotoxicity and proteasome peptidase activities were assessed in PC12 cells exposed to 50, 100, 150 mmol/L, 200 and 300 mmol/L ethanol. Results After 48 hours of treatment, ethanol inhibited proteasome peptidase activity in a dose-dependent manner at the concentration above 100 mmol/L. Moreover, the effect of ethanol on activities of proteasome was also in a time-dependent manner from 24 h. Cytotoxicity was still observed as ethanol concentrations increasing, started from 100 mmol/L, as assessed by MTT method. Conclusion Our results demonstrates ethanol may disturb the metabolism of protein by inhibiting proteasome peptidase activities, which is related to the toxic mechanism of ethanol on PC12 cells.