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SSeCKS promote beta-amyloid-induced PC12 cells neurotoxicity by up-regulating tau phosphorylation in Alzheimer’s disease

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Abstract

In Alzheimer’s disease, Beta-amyloid peptide (Aβ) could induce tau hyperphosphorylation which is the major cause of neuron apoptosis. However, the underlying mechanisms in the process remain unclear. In this study, Aβ-induced apoptosis and tau phosphorylation were investigated in differentiated PC12 cells. This Aβ-induced tau phosphorylation paralleled with the increase of expression and phosphorylation of Src-suppressed protein kinase C substrate (SSeCKS). By knocking down the expression of SSeCKS, Aβ-induced apoptosis and tau hyperphosphorylation in PC12 cells were partially rescued, and were increased further due to the overexpression of SSeCKS in PC12 cells. Also, the cell apoptosis and tau hyperphosphorylation were strongly decreased when the cells were pretreated with the protein kinase C inhibitor, Gö6983. In addition, Aβ-induced tau phosphorylation was also partially decreased due to the overexpression of SSeCKS in PC12cells. In summary, our data indicate that SSeCKS may play a critical role in Aβ-induced PC12 cells apoptosis through its phosphorylation.

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Acknowledgement

This study was supported by various institutions: he National Natural Science Foundation of China (No.30300099, No.30770488 and No.30870320); the Natural Science Foundation of Jiangsu province (No.BK2009156, No.BK2009157); the Special Research Grant (XK200723) for the Key Laboratory from the Department of Health, Jiangsu Province; the Natural science Foundation of Jiangsu Colleges and Universities Grant (09KJD310005); The Society and Technology Grew Project of Nantong City (S2008020); the Postgraduate Scientific Innovation Program of Nantong University (YKC09024).

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Authors and Affiliations

  1. Department of Osteology, The Second Affiliated Hospital of Nantong University, Jiangsu Province Key Laboratory of Neuroregeneration, Nantong University, Nantong, 226001, People’s Republic of China

    Zhiming Cui, Qin Shen & Xiaohong Li

  2. Department of Immunology, Medical College, Nantong University, Nantong, 226001, People’s Republic of China

    Tao Tao, Chun Cheng, Junling Yang, Yuhong Ji & Haiou Liu

  3. Department of Geriatics, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, Jiangsu, People’s Republic of China

    Aiguo Shen & Xiang Lu

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  1. Zhiming Cui
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  2. Tao Tao
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  3. Chun Cheng
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  4. Junling Yang
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  5. Qin Shen
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  7. Xiaohong Li
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  8. Haiou Liu
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  9. Aiguo Shen
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  10. Xiang Lu
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Correspondence to Aiguo Shen or Xiang Lu.

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The authors Zhiming Cui and Tao Tao contributed equally to this work.

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Cui, Z., Tao, T., Cheng, C. et al. SSeCKS promote beta-amyloid-induced PC12 cells neurotoxicity by up-regulating tau phosphorylation in Alzheimer’s disease. Mol Cell Biochem 340, 257–263 (2010). https://doi.org/10.1007/s11010-010-0425-6

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  • DOI: https://doi.org/10.1007/s11010-010-0425-6

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