Inhibition of PC12 cell redox activity is a specific,early indicator of the mechanism of beta-amyloid-mediated celldeath.
Open Access
- 15 February 1994
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 91 (4) , 1470-1474
- https://doi.org/10.1073/pnas.91.4.1470
Abstract
An in vitro tissue culture cell model system for investigating the biochemical mechanisms involved in the neurodegenerative actions of beta-amyloid has been established. Using rat pheochromocytoma PC12 cells, it was found that an early, specific response of cells to the beta-amyloid protein or the beta-amyloid fragment 25-35 was a potent inhibition of cellular redox activity, as measured by 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) reduction. This inhibitory response was rapid and occurred at nanomolar concentrations of peptide, concentrations at which no equivalent decreases in cell proliferation or cell survival were observed. The inhibition of PC12 cell MTT reduction was initially reversible upon removal of the peptide; if sustained for several days, however, by repeated peptide application, it became associated with a dramatic reduction in cell survival. Inhibition of MTT reduction may, therefore, be an early indicator of the mechanism of beta-amyloid-mediated cell death.Keywords
This publication has 30 references indexed in Scilit:
- Binding of human apolipoprotein E to synthetic amyloid beta peptide: isoform-specific effects and implications for late-onset Alzheimer disease.Proceedings of the National Academy of Sciences, 1993
- Apoptosis is induced by beta-amyloid in cultured central nervous system neurons.Proceedings of the National Academy of Sciences, 1993
- Gene Dose of Apolipoprotein E Type 4 Allele and the Risk of Alzheimer's Disease in Late Onset FamiliesScience, 1993
- Association of apolipoprotein E allele ϵ4 with late‐onset familial and sporadic Alzheimer's diseaseNeurology, 1993
- Alzheimer disease and the prion disorders amyloid beta-protein and prion protein amyloidoses.Proceedings of the National Academy of Sciences, 1993
- Apoptosis mediated neurotoxicity induced by chronic application of β amyloid fragment 25–35NeuroReport, 1993
- Apolipoprotein E: Binding to Soluble Alzheimer′s β-AmyloidBiochemical and Biophysical Research Communications, 1993
- Neurotoxicity of a prion protein fragmentNature, 1993
- Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease.Proceedings of the National Academy of Sciences, 1993
- Secretion of β-amyloid precursor protein cleaved at the amino terminus of the β-amyloid peptideNature, 1993