Study on the toxic mechanism of prion protein peptide 106-126 in neuronal and non neuronal cells.
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.
Dupiereux
Ingrid
I
Department of Human Histology, CRPP, University of Liège, Institute of Pharmacy-CHU, Sart Tilman, Liège, Belgium.
Zorzi
Willy
W
Rachidi
Walid
W
Zorzi
Danièle
D
Pierard
Olivier
O
Lhereux
Bernard
B
Heinen
Ernst
E
Elmoualij
Benaïssa
B
D000818:Animals; D016923:Cell Death / Q000502:physiology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002490:Central Nervous System / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004351:Drug Resistance / Q000502:physiology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D009410:Nerve Degeneration / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010446:Peptide Fragments / Q000378:metabolism / Q000633:toxicity*; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism; D017096:Prion Diseases / Q000378:metabolism* / Q000503:physiopathology; D011328:Prions / Q000378:metabolism / Q000633:toxicity*; D011817:Rabbits; D014162:Transfection; D019076:Transgenes / Q000235:genetics
D008563:Membrane Lipids; D010446:Peptide Fragments; D018621:PrPC Proteins; D011328:Prions; C082632:prion protein (106-126)