title: Treatment of SMB-S15 Cells with Resveratrol Efficiently Removes the PrP(Sc) Accumulation In Vitro and Prion Infectivity In Vivo.
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 PrP(Sc) 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 PrP(Sc) in a dose-dependent manner, with EC50 0.61 μM. Meanwhile, PrP(Sc) signals in SMB-S15 cells treated with 5 and 10 μM resveratrol maintained undetectable after drug withdrawal, indicating that the removal of PrP(Sc) 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 PrP(Sc) 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 PrP(Sc) to resveratrol highlights its potential role in prion therapeutics.
authors.affiliation: 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.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, 310003, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: 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.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, 310003, People's Republic of China.
authors.forename: Bao-Yun
authors.initials: BY
authors.lastname: Zhang
authors.affiliation: 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.|Shandong International Travel Health Care Center, Shandong Entry-Exit Inspection and Quarantine Bureau, Qingdao, 266001, People's Republic of China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 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.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, 310003, People's Republic of China.
authors.forename: Kang
authors.initials: K
authors.lastname: Xiao
authors.affiliation: 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.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Chen
authors.affiliation: 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.|Department of Immunology, School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.affiliation: 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.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, 310003, People's Republic of China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Shi
authors.affiliation: 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. dongxp238@sina.com.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, 310003, People's Republic of China. dongxp238@sina.com.|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. dongxp238@sina.com.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Dong
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D002460:Cell Line; D007276:Injections, Intraventricular; D051379:Mice; D018620:PrPSc Proteins / Q000378:metabolism*; D017096:Prion Diseases / Q000378:metabolism* / Q000473:pathology; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D034421:Sus scrofa
chemical_list: D018620:PrPSc Proteins; D013267:Stilbenes; D000077185:Resveratrol
keywords: Infectivity; Prion; Resveratrol; Scrapie; Therapy