PrP fragment 106-126 is toxic to cerebral endothelial cells expressing PrPC

A hydrophobic, fibrillogenic peptide fragment of human prion protein (PrP10 6-126) had in vitro toxicity to neurons expressing cellular prion protein ( PrPC). In this study, we proved that primary cultures of mouse cerebral end othelial cells (MCEC) express PrPC. Incubation of MCEC with PrP106-126 (25- 200 muM) caused a dose-dependent toxicity assessed by 3-(4,5dimethylthiazol -2-yl)-2,5-diphenyltetrazlium bromide (MTT) assay, lactate dehydrogenase re lease, bis-benzimide staining for nuclear morphology, and trypan blue exclu sion test. Pentosan polysulphate (50-100 mug/ml), a drug effective in scrap ie prophylaxis, dose-dependently attenuated the injury. MCEC cultures from mice homogenous for the disrupted PrP gene were resistant to the toxicity o f PrP106-126. In conclusion, cerebral endothelium expressing PrPC may be di rectly damaged during spongiform encephalopathies. NeuroReport 11:3931-3936 (C) 2000 Lippincott Witliams & Wilkins.