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Treatment of SMB-S15 Cells with Resveratrol Efficiently Removes the PrPSc Accumulation In Vitro and Prion Infectivity In Vivo

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Abstract

Prion diseases are transmissible and invariably fatal neurodegenerative disorders, which still lack of efficacious prophylactic and therapeutic tools. Our previous study has proposed that the natural phytoalexin, resveratrol, can reduce the amounts of PrPSc in a scrapie-infected cell line SMB-S15. To address its anti-prion efficacy, the inhibitive activity of resveratrol on prion accumulation in vitro and prion infectivity in vivo was analyzed in the present study. Exposure of SMB-S15 cells to various concentrations of resveratrol (0.25 to 200 μM) reduced and even removed cellular PrPSc in a dose-dependent manner, with EC50 0.61 μM. Meanwhile, PrPSc signals in SMB-S15 cells treated with 5 and 10 μM resveratrol maintained undetectable after drug withdrawal, indicating that the removal of PrPSc in SMB-S15 cells by resveratrol is irreversible. Furthermore, the lysates of SMB-S15 cells exposed to 10 μM resveratrol for 2 and 7 days were intracerebrally inoculated into CD1 mice. All mice (n = 9) infected with SMB-S15 cells without treatment of resveratrol appeared typical experimental scrapie symptoms from 155 to 228 day post inoculation (dpi), while all mice (n = 9) inoculated with SMB-S15 cells treated with resveratrol for 7 days maintained healthy by the end of observations (284 dpi). PrP-specific Western blots and neuropathological tests did not identify PrPSc or prion disease-associated pathological abnormality in the brains of mice inoculated with 7-day resveratrol-treated SMB-S15 cells. It indicates that the prion infectivity of SMB-S15 onto CD1 mice is eradicated by 1-week resveratrol treatment. Sensitivity of PrPSc to resveratrol highlights its potential role in prion therapeutics.

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Acknowledgments

This work was supported by Chinese National Natural Science Foundation Grants (81100980, 81301429), SKLID Development Grant (2013SKLID402, 2012SKLID102), and China Mega-Project for Infectious Disease (2011ZX10004-101, 2012ZX10004215).

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Authors and Affiliations

  1. State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing, 102206, People’s Republic of China

    Jing Wang, Bao-Yun Zhang, Jin Zhang, Kang Xiao, Li-Na Chen, Hui Wang, Jing Sun, Qi Shi & Xiao-Ping Dong

  2. Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, 310003, People’s Republic of China

    Jing Wang, Bao-Yun Zhang, Kang Xiao, Qi Shi & Xiao-Ping Dong

  3. Shandong International Travel Health Care Center, Shandong Entry-Exit Inspection and Quarantine Bureau, Qingdao, 266001, People’s Republic of China

    Jin Zhang

  4. Department of Immunology, School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, People’s Republic of China

    Hui Wang

  5. Chinese Academy of Sciences, Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, People’s Republic of China

    Xiao-Ping Dong

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  1. Jing Wang
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Correspondence to Xiao-Ping Dong.

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Wang, J., Zhang, BY., Zhang, J. et al. Treatment of SMB-S15 Cells with Resveratrol Efficiently Removes the PrPSc Accumulation In Vitro and Prion Infectivity In Vivo. Mol Neurobiol 53, 5367–5376 (2016). https://doi.org/10.1007/s12035-015-9464-z

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  • DOI: https://doi.org/10.1007/s12035-015-9464-z

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