Cytoskeleton Elements Contribute to Prion Peptide-Induced Endothelial Barrier Breakdown in a Blood–Brain Barrier In Vitro System

Itzik Cooper; Katayun Cohen-Kashi Malina; Yishai Levin; Alexandra Gabashvili; Boaz Mohar; Alfredo Cagnotto; Mario Salmona; Vivian I. Teichberg

doi:10.3390/ijms232012126

Cytoskeleton Elements Contribute to Prion Peptide-Induced Endothelial Barrier Breakdown in a Blood–Brain Barrier In Vitro System

Itzik Cooper^*, Katayun Cohen-Kashi Malina, Yishai Levin, Alexandra Gabashvili, Boaz Mohar, Alfredo Cagnotto, Mario Salmona, Vivian I. Teichberg

^*Corresponding author for this work

Department of Brain Sciences

Research output: Contribution to journal › Article › peer-review

Abstract

The mechanisms involved in the interaction of PrP 106-126, a peptide corresponding to the prion protein amyloidogenic region, with the blood–brain barrier (BBB) were studied. PrP 106-126 treatment that was previously shown to impair BBB function, reduced cAMP levels in cultured brain endothelial cells, increased nitric oxide (NO) levels, and changed the activation mode of the small GTPases Rac1 (inactivation) and RhoA (activation). The latter are well established regulators of endothelial barrier properties that act via cytoskeletal elements. Indeed, liquid chromatography-mass spectrometry (LC-MS)-based proteomic profiling study revealed extensive changes in expression of cytoskeleton-related proteins. These results shed light on the nature of the interaction between the prion peptide PrP 106-126 and the BBB and emphasize the importance of the cytoskeleton in endothelium response to prion- induced stress.

Original language	English
Article number	12126
Number of pages	15
Journal	International Journal of Molecular Sciences
Volume	23
Issue number	20
DOIs	https://doi.org/10.3390/ijms232012126
Publication status	Published - 12 Oct 2022

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title = "Cytoskeleton Elements Contribute to Prion Peptide-Induced Endothelial Barrier Breakdown in a Blood–Brain Barrier In Vitro System",

abstract = "The mechanisms involved in the interaction of PrP 106-126, a peptide corresponding to the prion protein amyloidogenic region, with the blood–brain barrier (BBB) were studied. PrP 106-126 treatment that was previously shown to impair BBB function, reduced cAMP levels in cultured brain endothelial cells, increased nitric oxide (NO) levels, and changed the activation mode of the small GTPases Rac1 (inactivation) and RhoA (activation). The latter are well established regulators of endothelial barrier properties that act via cytoskeletal elements. Indeed, liquid chromatography-mass spectrometry (LC-MS)-based proteomic profiling study revealed extensive changes in expression of cytoskeleton-related proteins. These results shed light on the nature of the interaction between the prion peptide PrP 106-126 and the BBB and emphasize the importance of the cytoskeleton in endothelium response to prion- induced stress.",

author = "Itzik Cooper and {Cohen-Kashi Malina}, Katayun and Yishai Levin and Alexandra Gabashvili and Boaz Mohar and Alfredo Cagnotto and Mario Salmona and Teichberg, {Vivian I.}",

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T1 - Cytoskeleton Elements Contribute to Prion Peptide-Induced Endothelial Barrier Breakdown in a Blood–Brain Barrier In Vitro System

AU - Cooper, Itzik

AU - Cohen-Kashi Malina, Katayun

AU - Levin, Yishai

AU - Gabashvili, Alexandra

AU - Mohar, Boaz

AU - Cagnotto, Alfredo

AU - Salmona, Mario

AU - Teichberg, Vivian I.

PY - 2022/10/12

Y1 - 2022/10/12

N2 - The mechanisms involved in the interaction of PrP 106-126, a peptide corresponding to the prion protein amyloidogenic region, with the blood–brain barrier (BBB) were studied. PrP 106-126 treatment that was previously shown to impair BBB function, reduced cAMP levels in cultured brain endothelial cells, increased nitric oxide (NO) levels, and changed the activation mode of the small GTPases Rac1 (inactivation) and RhoA (activation). The latter are well established regulators of endothelial barrier properties that act via cytoskeletal elements. Indeed, liquid chromatography-mass spectrometry (LC-MS)-based proteomic profiling study revealed extensive changes in expression of cytoskeleton-related proteins. These results shed light on the nature of the interaction between the prion peptide PrP 106-126 and the BBB and emphasize the importance of the cytoskeleton in endothelium response to prion- induced stress.

AB - The mechanisms involved in the interaction of PrP 106-126, a peptide corresponding to the prion protein amyloidogenic region, with the blood–brain barrier (BBB) were studied. PrP 106-126 treatment that was previously shown to impair BBB function, reduced cAMP levels in cultured brain endothelial cells, increased nitric oxide (NO) levels, and changed the activation mode of the small GTPases Rac1 (inactivation) and RhoA (activation). The latter are well established regulators of endothelial barrier properties that act via cytoskeletal elements. Indeed, liquid chromatography-mass spectrometry (LC-MS)-based proteomic profiling study revealed extensive changes in expression of cytoskeleton-related proteins. These results shed light on the nature of the interaction between the prion peptide PrP 106-126 and the BBB and emphasize the importance of the cytoskeleton in endothelium response to prion- induced stress.

U2 - 10.3390/ijms232012126

DO - 10.3390/ijms232012126

M3 - Article

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SN - 1422-0067

VL - 23

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

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M1 - 12126

ER -

Cytoskeleton Elements Contribute to Prion Peptide-Induced Endothelial Barrier Breakdown in a Blood–Brain Barrier In Vitro System

Abstract

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