PrP fragment 106-126 is toxic to cerebral endothelial cells expressing PrP(C).
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 microM) 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 microg/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.
Deli
M A
MA
Department of Pharmacology 1, School of Medicine, Nagasaki University, Japan.
Sakaguchi
S
S
Nakaoke
R
R
Abrahám
C S
CS
Takahata
H
H
Kopacek
J
J
Shigematsu
K
K
Katamine
S
S
Niwa
M
M
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000166:cytology* / Q000201:enzymology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004727:Endothelium / Q000166:cytology* / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010426:Pentosan Sulfuric Polyester / Q000494:pharmacology; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000633:toxicity*; D011328:Prions / Q000037:antagonists & inhibitors / Q000633:toxicity*; D013778:Tetrazolium Salts; D013844:Thiazoles
D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D010446:Peptide Fragments; D011328:Prions; D013778:Tetrazolium Salts; D013844:Thiazoles; C082632:prion protein (106-126); D010426:Pentosan Sulfuric Polyester; D007770:L-Lactate Dehydrogenase; C022616:thiazolyl blue