title: The propagation of hamster-adapted scrapie PrPSc can be enhanced by reduced pyridine nucleotide in vitro.
abstract: Transmissible spongiform encephalopathies (TSEs), or prion diseases, are fatal neurodegenerative disorders caused by an infectious agent termed a prion, which can convert normal cellular prion protein (PrP(C)) into a pathologically misfolded isoform (PrP(Sc)). Taking advantage of protein misfolding cyclic amplification (PMCA), a series of experiments was conducted to investigate the possible influences of pyridine nucleotides on the propagation activities of hamster-adapted scrapie agents 263K and 139A in vitro using normal hamster brain homogenates and recombinant hamster PrP as the substrates. The results showed that PrP(Sc) from both scrapie agent 263K- and 139A-infected brains propagated more efficiently in PMCA with the addition of reduced NADPH, showing an obvious dose-dependent enhancement. Reduced NADH also prompted PrP(Sc) propagation, whereas NADP, NAD and vitamin C failed. Moreover, following incubation with NADPH, recombinant hamster PrP could be efficiently converted into the proteinase K-resistant form when exposed to the trace of PrP(Sc) from infected hamsters. Our data provide evidence that the reduced pyridine nucleotide plays an important role in the propagation of prion and this process seems to target PrP(C) molecules.
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Beijing, China.
authors.forename: Song
authors.initials: S
authors.lastname: Shi
authors.forename: Chen-Fang
authors.initials: CF
authors.lastname: Dong
authors.forename: Chan
authors.initials: C
authors.lastname: Tian
authors.forename: Rui-Min
authors.initials: RM
authors.lastname: Zhou
authors.forename: Kun
authors.initials: K
authors.lastname: Xu
authors.forename: Bao-Yun
authors.initials: BY
authors.lastname: Zhang
authors.forename: Chen
authors.initials: C
authors.lastname: Gao
authors.forename: Jun
authors.initials: J
authors.lastname: Han
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Dong
mesh_terms: D000818:Animals; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D009249:NADP / Q000378:metabolism; D009711:Nucleotides / Q000494:pharmacology*; D010084:Oxidation-Reduction; D018620:PrPSc Proteins / Q000096:biosynthesis*; D011725:Pyridines / Q000494:pharmacology*
chemical_list: D009711:Nucleotides; D018620:PrPSc Proteins; D011725:Pyridines; D009249:NADP