Department of Neurobiology, Ministry of Education, Xuanwu Hospital of China Capital Medical University, Beijing, China.
Acta Neurol Belg. 2011 Jun;111(2):130-5.
Previous studies have shown that over-expression of alpha-Synuclein (alpha-Syn), a protein whose abnormality is implicated in the pathogenesis of Parkinson's disease (PD), reduces tyrosine hydroxylase (TH) expression and dopamine synthesis. To explore the possible mechanism for the regulation of TH expression by alpha-Syn, luciferase reporter gene carrying a -493/+27bp fragment of human TH gene (pGL3-TH520) and pcDNA carrying halpha-Syn gene (pcDNA-halpha-Syn) were co-transfected into T293 cells. The results showed that alpha-Syn was only detected in pcDNA-halpha-Syn-transfected cells but not in pcDNA vector control cells. In alpha-Syn-transfected cells, the luciferase activity was dramatically reduced compared with the vector control cells. These results suggest that alpha-Syn may function as a negative regulator for TH expression by affecting the activity of TH promoter.
先前的研究表明，在帕金森病（PD）发病机制中异常的蛋白α-突触核蛋白（α-Syn）的过表达会降低酪氨酸羟化酶（TH）的表达和多巴胺的合成。为了探究α-Syn 调节 TH 表达的可能机制，将携带人类 TH 基因 -493/+27bp 片段的荧光素酶报告基因（pGL3-TH520）和携带 α-Syn 基因的 pcDNA（pcDNA-halpha-Syn）共转染到 T293 细胞中。结果显示，仅在 pcDNA-halpha-Syn 转染的细胞中检测到 α-Syn，而在 pcDNA 载体对照细胞中未检测到。在 α-Syn 转染的细胞中，与载体对照细胞相比，荧光素酶活性显著降低。这些结果表明，α-Syn 可能通过影响 TH 启动子的活性而作为 TH 表达的负调节剂。
