组蛋白脱乙酰化酶在α-突触核蛋白抑制酪氨酸羟化酶表达中的作用  

Histone Deacetylase Maybe Involved in the Mechanism of Inhibition of Tyrosine Hydroxylase Expression in α-Synuclein-Transfected Dopaminergic Neuronal Cells

作　　者：王雪梅[1] 陈彪[2] 

机构地区：[1]首都医科大学宣武医院神经内科 [2]首都医科大学宣武医院神经生物学室

出　　处：《首都医科大学学报》2006年第4期476-479,共4页Journal of Capital Medical University

基　　金：国家自然科学基金重点项目(30430280);国家重点基础研究发展"九七三"项目(G2000057005)资助课题

摘　　要：目的探讨组蛋白脱乙酰化酶(histone deacetylase,HDAC)参与α-突触核蛋白(-αsynuclein,-αSyn)的过表达抑制酪氨酸羟化酶(tyrosine hydroxylase,TH)的可能机制。方法利用HDAC活性检测试剂盒检测MES 23.5多巴胺能神经细胞系和稳定转染-αSyn的细胞中HDAC的活性差异,应用Western-blot及RT-PCR检测转染-αSyn细胞系中HDAC抑制剂———曲古抑菌素A(trichostatin A,TSA)对TH表达的影响。结果在转染-αSyn的细胞系中HDAC的活性显著高于未转染组;TSA增加了转染细胞内TH蛋白和mRNA的表达(P<0.05)。结论HDAC参与了多巴胺能神经元中-αSyn抑制TH表达的机制。Objective To investigate the mechanism of inhibition of tyrosine hydroxylase （TH） expression in α-Syntransfected dopaminergic neuronal cells, specifically whether or not α-Syn inhibits TH activity through affecting histone deacetylase（HDAC）. Methods Histone deacetylase activity assay kit was used to measure the difference of HDAC activity in transfected cells and control cells. After treatment with the inhibitor of HDAC （TSA） in transfected cells, the expression of TH was determined by RT-PCR and Western-blot, respectively. Results The HDAC activity in the transfected cells was significantly higher than in the control cells. After inhibiting the HDAC activity in transfected cells by TSA to the level of control cells, the expression of TH was up-regulated both at mRNA and protein levels. Conclusion These results suggested that HDAC was involved in the mechanism of inhibition of tyrosine hydroxylase expression in α-Syn-transfected dopaminergic neuronal cells.

关 键 词：Α-突触核蛋白 酪氨酸羟化酶 组蛋白脱乙酰化酶 帕金森病 

分 类 号：R742.5[医药卫生—神经病学与精神病学]