机构：[a]Beijing Institute for Neuroscience, Capital Medical University, Beijing Center of Neural Regeneration and Repair, Key Laboratory for Neuro degenerative Disease of the Ministry of Education, Beijing,China[b]Beijing Institute of Geriatrics, Xuanwu Hospital of the CMU, Beijing, China老年医学科首都医科大学宣武医院[c]Division of Psychobiology, Tokyo Institute of Psychiatry, Tokyo156-8585,Japan
Hyperphosphorylated alpha-synuclein is considered an important event in the pathogenesis of Parkinson's disease but its function remains elusive. In this study we provide evidence that tyrosine hydroxylase (TH) expression was unaffected by overexpression of wild-type and phospho-mimic mutant alpha-synuclein (S129D) in dopaminergic MN9D cells. However, alpha-synuclein overexpression evidently inhibited TH phosphorylation at Ser40 and dopamine synthesis, while alpha-synuclein (S129D) mutant enhanced TH phosphorylation and dopamine synthesis. This phospho-mimic mutant prevented wild-type alpha-synuclein cytotoxicity to MN9D cells, which might be due to aggregation of mutant alpha-synuclein in the cytoplasm and nuclei. These results demonstrated that phosphorylation at Ser129 was involved in the regulation of TH activity, as well as in eliminating the neurotoxicity of wild-type alpha-synuclein overexpression in MN9D cells. (C) 2009 Elsevier GmbH. All rights reserved.
基金：
study was supported by grants from The National Basic Research Program of China (2006CB500706), the National High- Tech R&D Program of China (2006AA02A408), the National Natural Science Foundation of China (30670655, 30700199),
the National Ministry of Education (20060025004), the Beijing of Natural Science Foundation and Municipal Education Commission (7082011, KM200610025002),
and Funding Project for Academic Human Resources Development in Institutions of Higher Learning under Jurisdiction of Beijing Municipality PHR (IHLB).
第一作者机构：[a]Beijing Institute for Neuroscience, Capital Medical University, Beijing Center of Neural Regeneration and Repair, Key Laboratory for Neuro degenerative Disease of the Ministry of Education, Beijing,China
通讯作者：
通讯机构：[a]Beijing Institute for Neuroscience, Capital Medical University, Beijing Center of Neural Regeneration and Repair, Key Laboratory for Neuro degenerative Disease of the Ministry of Education, Beijing,China
推荐引用方式(GB/T 7714)：
Bo Wu,QiLiu,ChunliDuan,et al.Phosphorylation of alpha-synuclein upregulates tyrosine hydroxylase activity in MN9D cells[J].ACTA HISTOCHEMICA.2011,113(1):32-35.doi:10.1016/j.acthis.2009.07.007.
APA：
Bo Wu,QiLiu,ChunliDuan,YaohuaLi,ShunYu...&HuiYang.(2011).Phosphorylation of alpha-synuclein upregulates tyrosine hydroxylase activity in MN9D cells.ACTA HISTOCHEMICA,113,(1)
MLA：
Bo Wu,et al."Phosphorylation of alpha-synuclein upregulates tyrosine hydroxylase activity in MN9D cells".ACTA HISTOCHEMICA 113..1(2011):32-35
