蛋白酶体抑制剂对神经细胞的双重作用  

The Double Effects of Proteasome Inhibitor on Neuron

作　　者：曹三勇[1,2] 徐胜利 陈彪[1,2] 

机构地区：[1]首都医科大学宣武医院神经内科,100053 [2]北京市老年病研究所神经生物学室

出　　处：《脑与神经疾病杂志》2006年第4期274-277,298,共5页Journal of Brain and Nervous Diseases

基　　金：国家自然科学基金重点资助项目(30430280);国家自然科学基金资助项目(30371574);北京市自然科学基金重点资助项目(7031002)

摘　　要：目的探索蛋白酶体抑制剂在不同浓度时对多巴胺能神经元的作用及原因。方法用6-羟多巴(6-OHDA)50uM处理的人SH-SY5Y细胞作为细胞受损伤的模型,加用不同浓度的蛋白酶体抑制剂lactacystin,镜下细胞计数和SRB法测定细胞活力,平行对照组测定蛋白酶体活性。用选择性MEKl/2抑制剂PD98059验证蛋白酶体抑制剂是否通过MAPK途径起作用。结果蛋白酶体抑制剂lactacystin在0.1、0.25、0.5uM浓度时提高细胞存活率,在2、5uM时降低细胞存活率,相应的蛋白酶体活性分别是对照组的83.43%、73.84%、66.14%、24.11%、12.36%,加用PD98059后,0.25、0.5uMlactacystin的保护作用被阻断。结论蛋白酶体抑制剂在低浓度时对多巴胺能神经元有保护作用,高浓度时对多巴胺能神经元有毒性作用,这种不同作用的原因可能与蛋白酶体抑制的程度有关。蛋白酶体抑制剂的保护作用可能通过MAPK途径起作用。Objective： To explore the effects of proteasome inhibitor on dopaminergic neuron at different concentration and its possible underlying reason. Methods： SH-SYSY 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 dopamin- ergic 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.

关 键 词：SH—SY5Y帕金森病 泛素-蛋白酶体系统 蛋白酶体抑制剂 

分 类 号：R74[医药卫生—神经病学与精神病学]