title: The effects of lysosomal and proteasomal inhibitors on abnormal forms of prion protein degradation in murine macrophages.
abstract: It has been reported that macrophages degrade infectious forms of prion protein (PrP(Sc) ). In order to investigate the mechanisms underlying PrP(Sc) degradation in macrophages, the effects of lysosomal and proteasomal inhibitors on macrophage cell lines which were incubated with scrapie-affected brain homogenate were studied. PrP(Sc) degradation was inhibited in the presence of both proteasomal and lysosomal inhibitors. Indirect fluorescence assays to determine the cellular localization of PrP(Sc) were undertaken. PrP(Sc) colocalized with the lysosomal membrane protein Lamp-1 and ubiquitin, a protein that is related to the proteasome. The present data indicate that macrophages might degrade PrP(Sc) via the lysosomal and proteasomal pathways.
authors.affiliation: Laboratory of Food and Environmental Hygiene, Gifu University, Gifu City, Gifu, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Sassa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamasaki
authors.forename: Motohiro
authors.initials: M
authors.lastname: Horiuchi
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Inoshima
authors.forename: Naotaka
authors.initials: N
authors.lastname: Ishiguro
mesh_terms: D000818:Animals; D002460:Cell Line; D051907:Lysosomal Membrane Proteins / Q000502:physiology; D008247:Lysosomes / Q000187:drug effects / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D018620:PrPSc Proteins / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000502:physiology*; D061988:Proteasome Inhibitors; D025801:Ubiquitin / Q000502:physiology; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D051907:Lysosomal Membrane Proteins; D018620:PrPSc Proteins; D046988:Proteasome Endopeptidase Complex; D061988:Proteasome Inhibitors; D025801:Ubiquitin; C489116:LAMP1 protein, human; D052118:Lysosomal-Associated Membrane Protein 1