PrP fragment 106-126 is toxic to cerebral endothelial cells expressing PrP(C)

Mária A. Deli, Suehiro Sakaguchi, Ryota Nakaoke, Csongor S. Ábrahám, Hideaki Takahata, Juraj Kopaček, Kazuto Shigematsu, Shigeru Katamine, Masami Niwa

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33 Citations (Scopus)

Abstract

A hydrophobic, fibrillogenic peptide fragment of human prion protein (PrP106-126) had in vitro toxicity to neurons expressing cellular prion protein (PrP(C)). In this study, we proved that primary cultures of mouse cerebral endothelial cells (MCEC) express PrP(C). Incubation of MCEC with PrP106-126 (25-200 μM) caused a dose-dependent toxicity assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, lactate dehydrogenase release, bis-benzimide staining for nuclear morphology, and trypan blue exclusion test. Pentosan polysulphate (50-100 μg/ml), a drug effective in scrapie prophylaxis, dose-dependently attenuated the injury. MCEC cultures from mice homogenous for the disrupted PrP gene were resistant to the toxicity of PrP106-126. In conclusion, cerebral endothelium expressing PrP(C) may be directly damaged during spongiform encephalopathies. (C) 2000 Lippincott Williams and Wilkins.

Original languageEnglish
Pages (from-to)3931-3936
Number of pages6
JournalNeuroreport
Volume11
Issue number17
Publication statusPublished - Nov 27 2000

Keywords

  • Cellular prion protein
  • Cerebral endothelial cells
  • Pentosan polysulphate
  • PrP fragment 106-126
  • Toxicity

ASJC Scopus subject areas

  • Neuroscience(all)

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    Deli, M. A., Sakaguchi, S., Nakaoke, R., Ábrahám, C. S., Takahata, H., Kopaček, J., Shigematsu, K., Katamine, S., & Niwa, M. (2000). PrP fragment 106-126 is toxic to cerebral endothelial cells expressing PrP(C). Neuroreport, 11(17), 3931-3936.