Silencing alpha-synuclein gene expression enhances tyrosine hydroxylase activity in MN9D cells.
Silencing alpha-synuclein gene expression enhances tyrosine hydroxylase activity in MN9D cells.
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DOI：
10.1007/s11064-008-9599-7
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发表时间：
2008-07
影响因子：
4.4
通讯作者：
Yang, Hui
中科院分区：
文献类型：
--
作者：
Liu, Dongmei;Jin, Ling;Wang, Hao;Zhao, Huanying;Zhao, Chunli;Duan, Chunli;Lu, Lingling;Wu, Bo;Yu, Shun;Chan, Piu;Li, Yaohua;Yang, Hui
α-突触核蛋白（α-Synuclein）与帕金森病（Parkinson's disease，PD）的发病机制有关。以往的研究表明，α-synuclein可能通过下调多巴胺（DA）合成限速酶酪氨酸羟化酶（TH）的表达，参与多巴胺（DA）代谢的调节。在这项研究中，我们通过载体介导的RNA干扰构建了稳定沉默α-synuclein的MN 9D/α-SYN−细胞，并研究了其对DA代谢的影响。我们发现MN 9D、MN 9D/α-SYN−和MN 9D/CON细胞之间TH蛋白和mRNA水平没有显著差异，表明沉默α-突触核蛋白表达不影响TH基因表达。然而，在MN 9D/α-SYN−细胞中观察到磷酸化TH、胞质3，4-二羟基苯丙氨酸（l-DOPA）和DA水平的显著增加。我们的数据表明，TH活性和DA的生物合成增强下调α-synuclein，表明α-synuclein可能作为一个负调节胞浆DA。就PD病理，功能性α-synuclein的损失可能会导致增加DA水平的神经元，可能会导致细胞损伤甚至死亡。
α-Synuclein has been implicated in the pathogenesis of Parkinson’s disease (PD). Previous studies have shown that α-synuclein is involved in the regulation of dopamine (DA) metabolism, possibly by down-regulating the expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in DA biosynthesis. In this study, we constructed α-synuclein stably silenced MN9D/α-SYN− cells by vector mediated RNA interference and examined its effects on DA metabolism. We found that there were no significant differences in TH protein and mRNA levels between MN9D, MN9D/α-SYN− and MN9D/CON cells, suggesting that silencing α-synuclein expression does not affect TH gene expression. However, significant increases in phosphorylated TH, cytosolic 3, 4-dihydroxyphenylalanine (l-DOPA) and DA levels were observed in MN9D/α-SYN− cells. Our data show that TH activity and DA biosynthesis were enhanced by down-regulation of α-synuclein, suggesting that α-synuclein may act as a negative regulator of cytosolic DA. With respect to PD pathology, a loss of functional α-synuclein may result in increased DA levels in neurons that may lead to cell injury or even death.
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影响因子：
11
作者：
Mezey, E;Dehejia, AM;Polymeropoulos, MH
通讯作者：
Polymeropoulos, MH
影响因子：
4.7
作者：
Drolet, RE;Behrouz, B;Goudreau, JL
通讯作者：
Goudreau, JL
影响因子：
5.3
作者：
Rajagopalan, S;Andersen, JK
通讯作者：
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影响因子：
56.9
作者：
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通讯作者：
Agami, R
影响因子：
4.8
作者：
Greenbaum, EA;Graves, CL;Giasson, BI
通讯作者：
Giasson, BI