Inhibition of tyrosine hydroxylase expression in α-synuclein-transfected dopaminergic neuronal cells

Yu, Shun; Zuo, Xiaohong; Li, Yaohua; Zhang, Chen; Zhou, Ming; Zhang, Yu Alex; Uéda, Kenji; Chan, Piu

doi:10.1016/j.neulet.2004.05.118

Cited by 102 publications

(83 citation statements)

References 36 publications

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“…Previous studies have shown that α-synuclein and tyrosine hydroxylase (TH) are coexpressed in the brain and dopaminergic cell lines and that α-synuclein may play a role in regulating dopamine synthesis (49,50). TH is also known to be expressed in neurons of the enteric nervous system, and TH mRNA was previously detected in intestinal PYY cells by real-time PCR (33,51).…”

Section: Resultsmentioning

confidence: 99%

α-Synuclein in gut endocrine cells and its implications for Parkinson’s disease

Chandra

Hiniker²,

Kuo³

et al. 2017

JCI Insight

194

176

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Section: Resultsmentioning

confidence: 99%

α-Synuclein in gut endocrine cells and its implications for Parkinson’s disease

Chandra

Hiniker²,

Kuo³

et al. 2017

JCI Insight

194

176

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“…α-Syn binds to tyrosine hydroxylase (TH), a rate-limiting enzyme in dopamine biosynthesis, and influences its activity [7] . The TH expression was greatly decreased in α-Syn-transfected dopaminergic cells [8] . These results revealed a close correlation between the function of α-Syn and dopamine metabolism.…”

Section: Introductionmentioning

confidence: 94%

Effect of α-synuclein on the promoter activity of tyrosine hydroxylase gene

Gao

et al. 2007

Neurosci. Bull.

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Objective To approach the associated mechanism by which α-synuclein (α-Syn) might regulate the metabolism of dopamine. Methods A DNA fragment, located at -495 to +25 of the human tyrosine hydroxylase (TH) gene, was amplified by PCR and inserted into the pGL 3 -Basic luciferase reporter vector. The recombinant plasmid pGL 3 -THprom was transfected into a dopaminergic cell line MES23.5 or a α-Syn over-expressed MES23.5 (named MES23.5/hα-Syn + ). The promoter activity was detected by the Dual Luciferase Assay System. Results The luciferase activities in the MES23.5 cells transfected with pGL 3 -Basic, pGL 3 -THprom, and pGL 3 -Control vectors were 5.60±0.67, 26.80±4.11, and 32.90±4.75, respectively. On the other hand, the luciferase activity of pGL 3 -THprom in the MES23.5 (26.80±4.11) was significantly higher than that in the MES23.5/hα-Syn + (14.40±0.61) (P<0.01). Conclusion These results indicate that the -495 to +25 region in the TH gene possesses promoter activity for controlling the gene expression, and that α-Syn may negatively regulate the metabolism of dopamine by affecting the function of TH promoter as a trans-acting factor.

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“…One theory suggested that -synuclein might be linked to PD via the regulation of dopamine (DA) homeostasis [19][20][21][22][23] . Several studies have proposed that -synuclein may be involved in regulating the biosynthesis, vesicles storage and release, as well as reuptake of DA [24][25][26][27][28][29][30][31] . In addition, -synuclein, as a chaperone, has been reported to interact with many other proteins, including 14-3-3, ERK1/2, parkin, etc.…”

Section: Introductionmentioning

confidence: 99%

RNA interference mediated silencing of α-synuclein in MN9D cells and its effects on cell viability

et al. 2008

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ObjectiveTo silence the expression of -synuclein in MN9D dopaminergic cells using vector mediated RNA interference (RNAi) and examined its effects on cell proliferation and viability. Methods We identified two 19-nucleotide stretches within the coding region of the -synuclein gene and designed three sets of oligonucleotides to generate doublestranded (ds) oligos. The ds oligos were inserted into the pENTR TM /H1/TO vector and transfected into MN9D dopaminergic cells. -Synuclein expression was detected by RT-PCR, real-time PCR, immunocytochemistry staining and Western blot. In addition, we measured cell proliferation using growth curves and cell viability by 3-(4, 5)-dimethylthiahiazo (-z-y1)-3, 5-diphenytetrazoliumromide (MTT). Results The mRNA and protein levels of -synuclein gene were significantly down-regulated in pSH2/ -SYN-transfected cells compared with control MN9D and pSH/CON-transfected MN9D cells, while pSH1/ -SYNtransfected cells showed no significant difference. Silencing -synuclein expression does not affect cell proliferation but may decrease cell viability. Conclusion Our results demonstrated pSH2/ -SYN is an effective small interfering RNA (siRNA) sequence and potent silencing of mouse -synuclein expression in MN9D cells by vector-based RNAi, which provides the tools for studying the normal function of -synuclein and examining its role in Parkinson's disease (PD) pathogenesis.-Synuclein may be important for the viability of MN9D cells, and loss of -synuclein may induce cell injury directly or indirectly.

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Inhibition of tyrosine hydroxylase expression in α-synuclein-transfected dopaminergic neuronal cells

Cited by 102 publications

References 36 publications

α-Synuclein in gut endocrine cells and its implications for Parkinson’s disease

α-Synuclein in gut endocrine cells and its implications for Parkinson’s disease

Effect of α-synuclein on the promoter activity of tyrosine hydroxylase gene

RNA interference mediated silencing of α-synuclein in MN9D cells and its effects on cell viability

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