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

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Abstract
A hydrophobic, fibrillogenic peptide fragment of human prion protein (PrP 106–126) had in vitro toxicity to neurons expressing cellular prion protein (PrPC). In this study, we proved that primary cultures of mouse cerebral endothelial cells (MCEC) express PrPC. Incubation of MCEC with PrP 106–126 (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 PrP 106–126. In conclusion, cerebral endothelium expressing PrPC may be directly damaged during spongiform encephalopathies.