Interactions of the prion peptide (PrP 106-126) with brain capillary endothelial cells: Coordinated cell killing and remodeling of intercellular junctions

Itzik Cooper, Katayun Cohen Kashi Malina, Alfredo Cagnotto, Gianfranco Bazzoni, Mario Salmona, Vivian I. Teichberg

Research output: Contribution to journalArticlepeer-review

Abstract

We studied here the interactions of PrP 106-126, a peptide corresponding to the prion protein (PrP) amyloidogenic region, with a blood-brain barrier in vitro model consisting of confluent porcine brain endothelial cells (PBEC). PrP 106-126 interacted selectively with PBEC via their luminal side, and caused cumulative cell death, as shown by lactate dehydrogenase release, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction, Caspase 3 induction and direct cell counting. In addition, PrP 106-126, but not its corresponding scrambled peptide, produced a 50% reduction of the trans-endothelial electrical resistance, while the PBEC maintained confluency. This process was accompanied by a 23% increase of PBEC average size and the selective disappearance from the cell borders of the junction proteins occludin, claudin-5 and VE-cadherin (but not ZO-1), as evaluated by immunostaining. These results fit with a mechanism by which PrP 106-126 initiates a coordinated cell killing process ultimately causing the remaining cells to undergo a coordinated remodeling of the intercellular junctions and an expansion of their cell territory.

Original languageEnglish
Pages (from-to)467-475
Number of pages9
JournalJournal of Neurochemistry
Volume116
Issue number4
DOIs
Publication statusPublished - Feb 2011

Keywords

  • blood-brain barrier
  • endothelial cells
  • prion
  • tight junctions
  • trans-endothelial resistance

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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