title: Infection of prions and treatment of PrP106-126 alter the endogenous status of protein 14-3-3 and trigger the mitochondrial apoptosis possibly via activating Bax pathway.
abstract: The 14-3-3 proteins are a family of highly homologous and ubiquitously expressed isoforms that are involved in a wide variety of physiological processes. 14-3-3 have showed actively molecular interaction with PrP and positive 14-3-3 is frequently observed in the cerebrospinal fluid (CSF) samples of the patients with sporadic Creutzfeldt-Jakob disease (CJD). However, the alterations of 14-3-3 in the brain tissues of patients with prion diseases remain little addressed. To address the possible change of brain 14-3-3 during prion infection, we firstly tested the levels of 14-3-3 in the brain tissues of scrapie agent 263 K infected hamsters. Obviously decreased 14-3-3 were observed in the samples of the infected animals, showing time-dependent reduction in the incubation period, while the amounts of S-nitrosylated 14-3-3 were increased in the brains collected at the late stage. A low level of 14-3-3 was also observed in the scrapie infectious cell line SMB-S15, accompanied with up-regulated Bax and down-regulated Bcl-2. Moreover, we found that treatment of PrP106-126 on the cultured cells decreased the cellular 14-3-3 and caused translocations of cellular Bax to the membrane fractions. Knockdown of cellular 14-3-3 sensitized the cultured cells to the challenge of PrP106-126. These data illustrate that significant down-regulation of brain 14-3-3 levels during prion infection may not only be a scenario of the terminal consequence of interacting with abnormal PrP(Sc) but may also participate in the pathogenesis of neuronal damage.
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Road, Beijing, 102206, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Shi
authors.forename: Qin-Qin
authors.initials: QQ
authors.lastname: Song
authors.forename: Peng
authors.initials: P
authors.lastname: Sun
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.forename: Juan
authors.initials: J
authors.lastname: Song
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Chen
authors.forename: Kang
authors.initials: K
authors.lastname: Xiao
authors.forename: Shao-Bin
authors.initials: SB
authors.lastname: Wang
authors.forename: Ya-Zhou
authors.initials: YZ
authors.lastname: Zhang
authors.forename: Gong-Qi
authors.initials: GQ
authors.lastname: Li
authors.forename: Lin-Jun
authors.initials: LJ
authors.lastname: Sheng
authors.forename: Bao-Dong
authors.initials: BD
authors.lastname: Wang
authors.forename: Ming-Zhi
authors.initials: MZ
authors.lastname: Lu
authors.forename: Jun
authors.initials: J
authors.lastname: Han
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Dong
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D006224:Cricetinae; D003412:Cricetulus; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000633:toxicity*; D017096:Prion Diseases / Q000378:metabolism* / Q000473:pathology; D011328:Prions / Q000633:toxicity*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis*
chemical_list: D048948:14-3-3 Proteins; C494826:BAX protein, human; D010446:Peptide Fragments; D011328:Prions; D051028:bcl-2-Associated X Protein; C082632:prion protein (106-126)