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Prion protein lacks robust cytoprotective activity in cultured cells

BACKGROUND: The physiological function of the cellular prion protein (PrP(C)) remains unknown. However, PrP(C )has been reported to possess a cytoprotective activity that prevents death of neurons and other cells after a toxic stimulus. To explore this effect further, we attempted to reproduce sever...

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Autores principales: Christensen, Heather M, Harris, David A
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2546390/
https://www.ncbi.nlm.nih.gov/pubmed/18718018
http://dx.doi.org/10.1186/1750-1326-3-11
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author Christensen, Heather M
Harris, David A
author_facet Christensen, Heather M
Harris, David A
author_sort Christensen, Heather M
collection PubMed
description BACKGROUND: The physiological function of the cellular prion protein (PrP(C)) remains unknown. However, PrP(C )has been reported to possess a cytoprotective activity that prevents death of neurons and other cells after a toxic stimulus. To explore this effect further, we attempted to reproduce several of the assays in which a protective activity of PrP had been previously demonstrated in mammalian cells. RESULTS: In the first set of experiments, we found that PrP over-expression had a minimal effect on the death of MCF-7 breast carcinoma cells treated with TNF-α and Prn-p(0/0 )immortalized hippocampal neurons (HpL3-4 cells) subjected to serum deprivation. In the second set of assays, we observed only a small difference in viability between cerebellar granule neurons cultured from PrP-null and control mice in response to activation of endogenous or exogenous Bax. CONCLUSION: Taken together, our results suggest either that cytoprotection is not a physiologically relevant activity of PrP(C), or that PrP(C)-dependent protective pathways operative in vivo are not adequately modeled by these cell culture systems. We suggest that cell systems capable of mimicking the neurotoxic effects produced in transgenic mice by N-terminally deleted forms of PrP or Doppel may represent more useful tools for analyzing the cytoprotective function of PrP(C).
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spelling pubmed-25463902008-09-20 Prion protein lacks robust cytoprotective activity in cultured cells Christensen, Heather M Harris, David A Mol Neurodegener Research Article BACKGROUND: The physiological function of the cellular prion protein (PrP(C)) remains unknown. However, PrP(C )has been reported to possess a cytoprotective activity that prevents death of neurons and other cells after a toxic stimulus. To explore this effect further, we attempted to reproduce several of the assays in which a protective activity of PrP had been previously demonstrated in mammalian cells. RESULTS: In the first set of experiments, we found that PrP over-expression had a minimal effect on the death of MCF-7 breast carcinoma cells treated with TNF-α and Prn-p(0/0 )immortalized hippocampal neurons (HpL3-4 cells) subjected to serum deprivation. In the second set of assays, we observed only a small difference in viability between cerebellar granule neurons cultured from PrP-null and control mice in response to activation of endogenous or exogenous Bax. CONCLUSION: Taken together, our results suggest either that cytoprotection is not a physiologically relevant activity of PrP(C), or that PrP(C)-dependent protective pathways operative in vivo are not adequately modeled by these cell culture systems. We suggest that cell systems capable of mimicking the neurotoxic effects produced in transgenic mice by N-terminally deleted forms of PrP or Doppel may represent more useful tools for analyzing the cytoprotective function of PrP(C). BioMed Central 2008-08-21 /pmc/articles/PMC2546390/ /pubmed/18718018 http://dx.doi.org/10.1186/1750-1326-3-11 Text en Copyright © 2008 Christensen and Harris; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Christensen, Heather M
Harris, David A
Prion protein lacks robust cytoprotective activity in cultured cells
title Prion protein lacks robust cytoprotective activity in cultured cells
title_full Prion protein lacks robust cytoprotective activity in cultured cells
title_fullStr Prion protein lacks robust cytoprotective activity in cultured cells
title_full_unstemmed Prion protein lacks robust cytoprotective activity in cultured cells
title_short Prion protein lacks robust cytoprotective activity in cultured cells
title_sort prion protein lacks robust cytoprotective activity in cultured cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2546390/
https://www.ncbi.nlm.nih.gov/pubmed/18718018
http://dx.doi.org/10.1186/1750-1326-3-11
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