Document Detail

Study on the toxic mechanism of prion protein peptide 106-126 in neuronal and non neuronal cells.
MedLine Citation:
PMID:  16786576     Owner:  NLM     Status:  MEDLINE    
A synthetic peptide corresponding to the 106-126 amyloidogenic region of the cellular human prion protein (PrP(c)) is useful for in vitro study of prion-induced neuronal cell death. The aim of the present work was to examine the implication of the cellular prion protein in the toxicity mechanism induced by PrP 106-126. The effect of PrP 106-126 was investigated both on human neuroblastoma SH-SY5Y cells and on SH-SY5Y overexpressing murine cellular prions (wtPrP). We show by metabolic assay tests and ATP assays that PrP(c) expression does not modulate the toxicity of the prion peptide. Moreover, we investigated the effect of this peptide on an established non neuronal model, rabbit kidney epithelial A74 cells that express a doxycycline-inducible murine PrP(c) gene. We show for the first time that the prion peptide 106-126 does not exert any toxic effect on this cell line in the presence or absence of doxycycline. Our results show that the PrP 106-126-induced cell alteration is independent of PrP(c) expression. Rather, it seems to act via an interaction with lipidic components of the plasma membrane as strengthened by our results showing the differential susceptibility of neuronal and non neuronal cell lines that significantly differ by their membrane fatty acid composition.
Ingrid Dupiereux; Willy Zorzi; Walid Rachidi; Danièle Zorzi; Olivier Pierard; Bernard Lhereux; Ernst Heinen; Benaïssa Elmoualij
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neuroscience research     Volume:  84     ISSN:  0360-4012     ISO Abbreviation:  J. Neurosci. Res.     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-08-24     Completed Date:  2006-11-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7600111     Medline TA:  J Neurosci Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  637-46     Citation Subset:  IM    
Department of Human Histology, CRPP, University of Liège, Institute of Pharmacy-CHU, Sart Tilman, Liège, Belgium.
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MeSH Terms
Cell Death / physiology
Cell Line, Tumor
Cell Membrane / chemistry,  metabolism
Central Nervous System / metabolism*,  pathology,  physiopathology
Drug Resistance / physiology
Epithelial Cells / drug effects,  metabolism*,  pathology
Membrane Lipids / chemistry,  metabolism*
Nerve Degeneration / metabolism,  physiopathology
Neurons / drug effects,  metabolism*,  pathology
Peptide Fragments / metabolism,  toxicity*
PrPC Proteins / genetics,  metabolism
Prion Diseases / metabolism*,  physiopathology
Prions / metabolism,  toxicity*
Transgenes / genetics
Reg. No./Substance:
0/Membrane Lipids; 0/Peptide Fragments; 0/PrPC Proteins; 0/Prions; 0/prion protein (106-126)

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