1. Academic Validation
  2. Interactions of the prion peptide (PrP 106-126) with brain capillary endothelial cells: coordinated cell killing and remodeling of intercellular junctions

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

  • J Neurochem. 2011 Feb;116(4):467-75. doi: 10.1111/j.1471-4159.2010.06934.x.
Itzik Cooper 1 Katayun Cohen-Kashi Malina Alfredo Cagnotto Gianfranco Bazzoni Mario Salmona Vivian I Teichberg
Affiliations

Affiliation

  • 1 Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel. itzik.cooper@weizmann.ac.il
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.

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