Journal of Capital Medical University ›› 2016, Vol. 37 ›› Issue (6): 777-783.doi: 10.3969/j.issn.1006-7795.2016.06.012

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Regulatory mechanism of Cornel iridoid glycoside on protein phosphatase 2A catalytic subunit C phosphorylation

Li Xuelian1,2,3,4,5, Yang Cuicui2,3,4,5, Zhang Lan2,3,4,5, Shi Jingshan1   

  1. 1. Key Laboratory for Basic Pharmacology of Ministry of Education, Zunyi Medical College, Zunyi 563000, Guizhou Province, China;
    2. Department of Pharmacology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China;
    3. Beijing Institute for Brain Disorders, Beijing 100053, China;
    4. Beijing Engineering Research Center for Nervous System Drugs, Beijing 100053, China;
    5. Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing 100053, China
  • Received:2016-10-14 Online:2016-12-21 Published:2016-12-16
  • Supported by:
    This study was supported by National Natural Science Foundation of China(81473373),Natural Science Foundation of Beijing(7132110),Major Project for Essential Drug Research and Development(2015ZX09101016001),Beijing Health and Technical High-level Personal Plan(2014-2-014),Beijing New Century Talented Person Project(008-0014),New Medical Disciplines Project of Beijing Education Committee(XK100270569).

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Abstract: Objective To investigate the mechanism of Cornel iridoid glycoside (CIG) inhibiting tau phosphorylation by up-regulating protein phosphatase 2A (PP2A) activity. Methods ① To determine optimal transfection conditions:transfecting Src plasmid DNA (0.2, 0.4, 0.6, 0.8 μg) into mouse neuro-2A cell (N2a cells) was performed to observe the effects of different quantity Src on phosphorylation of PP2A catalytic subunit C and tau phosphorylation. ② After transfecting 0.6 μg Src plasmid DNA into N2a cells 24 hours,the cells were incubated with CIG (50, 100, 200 μg/mL) 24h,then the effects of CIG on Src, PTP1B, p-PP2Ac and tau phosphorylation were observed. Results ① Expression of Src protein was significantly increased, the expression of p-PP2Ac was up-regulated and the expression of PP2A did not change when Src (0.2, 0.4, 0.6 μg) plasmid transfected into N2a cells, and the tau phosphorylation at the sites of Ser 199/202, Ser 396 increased significantly; In the N2a cells transfected with 0.8 μg Src, the expression of p-PP2Ac was increased apparently, the expression of PP2A was not changed, and the phosphorylation of tau at Ser 199/202 and Ser 396 sites was decreased. ② In the N2a cells transfected with 0.6 μg Src, the expression of Src was significantly increased, the expression of p-PP2Ac was significantly increased, and the tau phosphorylation at the sites of Ser 199/202, Thr 205, Thr 217 and Ser 396 sites increased significantly; CIG could inhibit the expression of p-PP2Ac, the expression of tau phosphorylation at the sites of Ser 199/202, Thr 205, Thr 217, and Ser 396. In addition, CIG can up-regulate PTP1B protein expression. Conclusion CIG had no obvious regulation effect on Src, but it could decrease the phosphorylation of PP2A catalytic subunit C by increasing the expression of PTP1B, and then increases the activity of PP2A, and further reduces the level of tau hyperphosphorylation. The inhibition of CIG on tau hyperphosphorylation, will bring broad application prospects on the treatment of AD.

Key words: Cornel iridoid glycoside, protein tyrosine kinase Src, protein phosphatase 2A, protein tyrosine phosphatase 1B, tau protein, Alzheimer's disease

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