Cytotoxicity of prion protein peptide (PrP106-126) differs in mechanism from the cytotoxic activity of the Alzheimer's disease amyloid peptide, A beta 25-35.
The abnormal form of the prion protein (PrPSc), a synthetic prion protein peptide fragment (PrP106-126) and fragments of the Alzheimer's protein precursor, APP, have been shown to be cytotoxic in vitro. We have used synchronous, clonal cell models originally developed to study the toxicity of the Alzheimer's disease amyloid peptide, A beta 25-35, to investigate the actions of PrP peptides. We found that the cytotoxicity of the PrP106-126 depends on its state of aggregation and the cellular expression of PrPc, and is independent of a loss of MTT reduction activity in the absence of cell death associated with the cellular effects of A beta 25-35. These factors may play a role in the lesion specificity of different pathological phenotypes of prion-protein related diseases.
Hope
J
J
BBSRC & MRC Neuropathogenesis Unit, BBSRC Institute for Animal Health, Edinburgh.
Shearman
M S
MS
Baxter
H C
HC
Chong
A
A
Kelly
S M
SM
Price
N C
NC
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects*; D002942:Circular Dichroism; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D007770:L-Lactate Dehydrogenase; D051379:Mice; D008969:Molecular Sequence Data; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D009498:Neurotoxins / Q000633:toxicity*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity*; D018621:PrPC Proteins / Q000096:biosynthesis* / Q000737:chemistry; D011328:Prions / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D014407:Tumor Cells, Cultured
D016229:Amyloid beta-Peptides; D009498:Neurotoxins; D010446:Peptide Fragments; D018621:PrPC Proteins; D011328:Prions; C074636:amyloid beta-protein (25-35); C082632:prion protein (106-126); D007770:L-Lactate Dehydrogenase