Silencing α-synuclein gene expression enhances tyrosine hydroxylase activity in MN9D cells

被引：49

作者：

Liu, Dongmei ^{[1
]}

Jin, Ling ^{[1
]}

Wang, Hao ^{[1
]}

Zhao, Huanying ^{[1
]}

Zhao, Chunli ^{[1
]}

Duan, Chunli ^{[1
]}

Lu, Lingling ^{[1
]}

Wu, Bo ^{[1
]}

Yu, Shun ^{[2
]}

Chan, Piu ^{[2
]}

Li, Yaohua ^{[2
]}

Yang, Hui ^{[1
]}

机构：

[1] Capital Med Univ, Beijing Ctr Neural Regenerat & Repair, Key Lab Neurodegenerat Dis, Beijing Inst Neurosci,Minist Educ, Beijing 100069, Peoples R China

[2] Capital Med Univ, Xuanwu Hosp, Beijing Inst Geriatr, Sino Japan Joint Lab Neurodegenerat Dis, Beijing 100053, Peoples R China

来源：

NEUROCHEMICAL RESEARCH | 2008年 / 33卷 / 07期

基金：

中国国家自然科学基金;

关键词：

alpha-synuclein; RNA interference; dopamine; Parkinson's disease;

D O I：

10.1007/s11064-008-9599-7

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

alpha-Synuclein has been implicated in the pathogenesis of Parkinson's disease (PD). Previous studies have shown that alpha-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 alpha-synuclein stably silenced MN9D/alpha-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/alpha-SYN(-) and MN9D/CON cells, suggesting that silencing alpha-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/alpha-SYN(-) stop cells. Our data show that TH activity and DA biosynthesis were enhanced by down-regulation of alpha-synuclein, suggesting that alpha-synuclein may act as a negative regulator of cytosolic DA. With respect to PD pathology, a loss of functional alpha-synuclein may result in increased DA levels in neurons that may lead to cell injury or even death.

引用

页码：1401 / 1409

页数：9

共 43 条

[31] α-synuclein and Parkinson's Disease [J].