Boyle 2012 Brain Res: Difference between revisions
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Revision as of 08:19, 5 April 2012
Boyle JP, Hettiarachchi NT, Wilkinson JA, Pearson HA, Scragg JL, Lendon C, Al-Owais MM, Kim CB, Myers DM, Warburton P, Peers C (2012) Cellular consequences of the expression of Alzheimer's disease-causing presenilin 1 mutations in human neuroblastoma (SH-SY5Y) cells. Brain Res 1443: 75-88 |
Boyle JP, Hettiarachchi NT, Wilkinson JA, Pearson HA, Scragg JL, Lendon C, Al-Owais MM, Kim CB, Myers DM, Warburton P, Peers C (2012) Brain Res
Abstract: Mutations in the presenilin 1 (PS1) gene lead to early-onset Alzheimer's disease with the S170F mutation causing the earliest reported age of onset. Expression of this, and other PS1 mutations, in SH-SY5Y cells resulted in significant loss of cellular viability compared to control cells. Basal Ca(2+) concentrations in PS1 mutants were never lower than controls and prolonged incubation in Ca(2+)-free solutions did not deplete Ca(2+) stores, demonstrating there was no difference in Ca(2+) leak from endoplasmic reticulum (ER) stores in PS1 mutants. Peak muscarine-evoked rises of [Ca(2+)](i) were variable, but the integrals were not significantly different, suggesting, while kinetics of Ca(2+) store release might be affected in PS1 mutants, store size was similar. However, when Ca(2+)-ATPase activity was irreversibly inhibited with thapsigargin, the S170F and ฮE9 cells showed larger capacitative calcium entry indicating a direct effect on Ca(2+) influx pathways. There was no significant effect of any of the mutations on mitochondrial respiration. Amyloid ฮฒ(Aฮฒ(1-40)) secretion was reduced, and Aฮฒ(1-42) secretion increased in the S170F cells resulting in a very large increase in the Aฮฒ42/40 ratio. This, rather than any potential disruption of ER Ca(2+) stores, is likely to explain the extreme pathology of this mutant. โข Keywords: Alzheimer's disease; presenilin 1 (PS1); Amyloid ฮฒ Aฮฒ(1-40) and Aฮฒ(1-42);
โข O2k-Network Lab: UK Leeds Peers C
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Stress:Cancer; Apoptosis; Cytochrome c"Cancer; Apoptosis; Cytochrome c" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property., Aging; Senescence"Aging; Senescence" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property. Organism: Human Tissue;cell: Neurons; Brain"Neurons; Brain" is not in the list (Heart, Skeletal muscle, Nervous system, Liver, Kidney, Lung;gill, Islet cell;pancreas;thymus, Endothelial;epithelial;mesothelial cell, Blood cells, Fat, ...) of allowed values for the "Tissue and cell" property. Preparation: Intact Cell; Cultured; Primary"Intact Cell; Cultured; Primary" is not in the list (Intact organism, Intact organ, Permeabilized cells, Permeabilized tissue, Homogenate, Isolated mitochondria, SMP, Chloroplasts, Enzyme, Oxidase;biochemical oxidation, ...) of allowed values for the "Preparation" property.
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