The effects of lysosomal and proteasomal inhibitors on abnormal forms of prion protein degradation in murine macrophages

Authors

  • Yukiko Sassa,

    1. Laboratory of Food and Environmental Hygiene, Faculty of Applied Biological Sciences, Gifu University, 1-1Yanagido, Gifu City, Gifu 501-1193
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  • Takeshi Yamasaki,

    1. Laboratory of Veterinary Hygiene, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo 060-0818, Japan
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  • Motohiro Horiuchi,

    1. Laboratory of Veterinary Hygiene, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo 060-0818, Japan
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  • Yasuo Inoshima,

    1. Laboratory of Food and Environmental Hygiene, Faculty of Applied Biological Sciences, Gifu University, 1-1Yanagido, Gifu City, Gifu 501-1193
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  • Naotaka Ishiguro

    1. Laboratory of Food and Environmental Hygiene, Faculty of Applied Biological Sciences, Gifu University, 1-1Yanagido, Gifu City, Gifu 501-1193
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Correspondence
N. Ishiguro, Laboratory of Food and Environmental Hygiene, Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu-city, Gifu 501-1193, Japan.
Tel./fax: +81 58 293 2864; email: ishiguna@gifu-u.ac.jp

ABSTRACT

It has been reported that macrophages degrade infectious forms of prion protein (PrPSc). In order to investigate the mechanisms underlying PrPSc degradation in macrophages, the effects of lysosomal and proteasomal inhibitors on macrophage cell lines which were incubated with scrapie-affected brain homogenate were studied. PrPSc degradation was inhibited in the presence of both proteasomal and lysosomal inhibitors. Indirect fluorescence assays to determine the cellular localization of PrPSc were undertaken. PrPSc 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 PrPSc via the lysosomal and proteasomal pathways.

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