Inhibition of tyrosine hydroxylase expression in α-synuclein-transfected dopaminergic neuronal cells
Inhibition of tyrosine hydroxylase expression in α-synuclein-transfected dopaminergic neuronal cells
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DOI：
10.1016/j.neulet.2004.05.118
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发表时间：
2004-08
影响因子：
2.5
通讯作者：
Shun Yu;X. Zuo;Yao-hua Li;Chen Zhang;Ming Zhou;Y. Zhang;K. Uéda;P. Chan
中科院分区：
文献类型：
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作者：
Shun Yu;X. Zuo;Yao-hua Li;Chen Zhang;Ming Zhou;Y. Zhang;K. Uéda;P. Chan
虽然α-突触核蛋白(α-Syn)的异常表达对多巴胺能神经元有毒性作用，但α-Synn的异常与酪氨酸羟化酶(TH)表达的相关性尚不清楚，TH是合成多巴胺神经递质的限速酶。本研究以野生型人α-Syn基因构建的MES23.5大鼠多巴胺能细胞系(h-α-Syn)为研究对象，探讨α-Syn与TH的关系。免疫细胞化学染色和免疫印迹显示hα-syn细胞TH的表达明显降低。Northern印迹证实，TH基因的表达水平也显著降低。TH蛋白水平的降低不影响细胞的生长和增殖。未观察到明显的细胞损伤或死亡。这些结果提示，α-Syn的异常表达可能抑制了多巴胺能细胞中TH的合成。
Although the aberrant expression of α-synuclein (α-Syn) is toxic to dopaminergic neurons, little is known about the correlation between the abnormality of α-Syn and the expression of tyrosine hydroxylase (TH), a rate-limiting enzyme for the synthesis of dopamine neurotransmitter. In this study, the MES23.5 rat dopaminergic cell line transfected with wild-type human α-Syn cDNA (hα-Syn) construct was used to investigate the association between α-Syn and TH. Immunocytochemical staining and Western blot for TH showed that the TH expression was greatly decreased in hα-Syn-transfected cells. Northern blot confirmed that the TH mRNA level was also dramatically reduced. Reduction of TH protein levels did not affect the growth and proliferation of the transfected cells. No apparent cell injury or death was observed. These results suggest that an abnormal expression of α-Syn may inhibit TH synthesis in dopaminergic cells.