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Deep Phosphoproteomic Measurements Pinpointing Drug Induced Protective Mechanisms in Neuronal Cells

文献类型：期刊论文

作者Yu, Chengli2,4,5; Gao, Jing2,5; Zhou, Yanting2,3,5; Chen, Xiangling2,4,5; Xiao, Ruoxuan2,4,5; Zheng, Jing3; Liu, Yansheng1; Zhou, Hu2,4,5
刊名FRONTIERS IN PHYSIOLOGY
出版日期2016-12-23
卷号7
关键词phosphoproteomics Alzheimer's disease drug effect mass spectrometry neutronal cells
ISSN号1664-042X
DOI10.3389/fphys.2016.00635
文献子类Article
英文摘要Alzheimer's disease (AD) is a progressive and irreversible neurological disorder that impairs the living quality of old population and even life spans. New compounds have shown potential inneuroprotective effects in AD, such as GFKP-19, a 2-pyrrolidone derivative which has been proved to enhance the memory of dysmnesia mouse. The molecular mechanisms remain to be established for these drug candidates. Large-scale phosphoproteomic approach has been evolved rapidly in the last several years, which holds the potential to provide a useful toolkit to understand cellular signaling underlying drug effects. To establish and test such a method, we accurately analyzed the deep quantitative phosphoproteome of the neuro-2a cells treated with and without GFKP-19 using triple SILAC labeling. A total of 14,761 Class I phosphosites were quantified between controls, damaged, and protected conditions using the high resolution mass spectrometry, with a decent inter-mass spectrometer reproducibility for even subtle regulatory events. Our data suggests that GFKP-19 can reverse A beta(25-35) induced phosphorylation change in neuro-2a cells, and might protect the neuron system in two ways: firstly, it may decrease oxidative damage and inflammation induced by NO via down regulating the phosphorylation of nitric oxide synthase NOS1 at S847; Secondly, it may decrease tau protein phosphorylation through down-regulating the phosphorylation level of MAPK14 at T180. All mass spectrometry data are available via ProteomeXchange with identifier PXDO05312.
WOS关键词ALZHEIMERS-DISEASE ; TAU-PROTEIN ; MITOCHONDRIAL DYSFUNCTION ; AMYLOID PEPTIDES ; NITRIC-OXIDE ; AMINO-ACIDS ; DATA SETS ; IN-VITRO ; PHOSPHORYLATION ; AGGREGATION
资助项目National Natural Science Foundation of China[21375138] ; National Natural Science Foundation of China[31300681] ; Ministry of Science and Technology of China[2013ZX09507001] ; "one hundred talent program" of Chinese Academy of Sciences[00000000] ; Strategic Priority Research Program of the Chinese Academy of Sciences, "Personalized Medicines Molecular Signature-based Drug Discovery and Development"[XDA12030203] ; Innovation Project of Instrument and Equipment Function Development from the Bureau of Goods, Chinese Academy of Sciences[YZ201542] ; Open Project Program of Jiangsu Key Laboratory of Pediatric Respiratory Disease, Nanjing University of Chinese Medicine[JKLPRD201404]
WOS研究方向Physiology
语种英语
WOS记录号WOS:000390375800001
出版者FRONTIERS MEDIA SA
源URL[http://119.78.100.183/handle/2S10ELR8/275760]  
专题分析化学研究室
通讯作者Liu, Yansheng; Zhou, Hu
作者单位1.Swiss Fed Inst Technol Zurich, Dept Biol, Inst Mol Syst Biol, Zurich, Switzerland
2.Chinese Acad Sci, Dept Analyt Chem, Shanghai, Peoples R China;
3.East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai, Peoples R China;
4.Univ Chinese Acad Sci, Chinese Acad Sci, Coll Pharm, Beijing, Peoples R China;
5.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai, Peoples R China;
推荐引用方式
GB/T 7714		 Yu, Chengli,Gao, Jing,Zhou, Yanting,et al. Deep Phosphoproteomic Measurements Pinpointing Drug Induced Protective Mechanisms in Neuronal Cells[J]. FRONTIERS IN PHYSIOLOGY,2016,7.
APA Yu, Chengli.,Gao, Jing.,Zhou, Yanting.,Chen, Xiangling.,Xiao, Ruoxuan.,...&Zhou, Hu.(2016).Deep Phosphoproteomic Measurements Pinpointing Drug Induced Protective Mechanisms in Neuronal Cells.FRONTIERS IN PHYSIOLOGY,7.
MLA Yu, Chengli,et al."Deep Phosphoproteomic Measurements Pinpointing Drug Induced Protective Mechanisms in Neuronal Cells".FRONTIERS IN PHYSIOLOGY 7(2016).

入库方式： OAI收割

来源：上海药物研究所

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