Cookies help us deliver our services. By using our services, you agree to our use of cookies. More information

Boyle 2012 Brain Res

From Bioblast
Publications in the MiPMap
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.

» PMID: 22297172

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 Ca2+ concentrations in PS1 mutants were never lower than controls and prolonged incubation in Ca2+-free solutions did not deplete Ca2+ stores, demonstrating there was no difference in Ca2+ leak from endoplasmic reticulum (ER) stores in PS1 mutants. Peak muscarine-evoked rises of [Ca2+](i) were variable, but the integrals were not significantly different, suggesting, while kinetics of Ca2+ store release might be affected in PS1 mutants, store size was similar. However, when Ca2+-ATPase activity was irreversibly inhibited with thapsigargin, the S170F and ΔE9 cells showed larger capacitative calcium entry indicating a direct effect on Ca2+ influx pathways. There was no significant effect of any of the mutations on mitochondrial respiration. Amyloid β(Aβ(1-40)) secretion was reduced, and Aβ(1-42) secretion increased in the S170F cells resulting in a very large increase in the Aβ42/40 ratio. This, rather than any potential disruption of ER Ca2+ stores, is likely to explain the extreme pathology of this mutant. Keywords: Alzheimer's disease, Presenilin 1 (PS1), Amyloid β Aβ(1-40) and Aβ(1-42), Endoplasmic reticulum

O2k-Network Lab: UK Leeds Peers C


Labels: MiParea: Respiration, nDNA;cell genetics, mt-Medicine  Pathology: Aging;senescence, Alzheimer's, Neurodegenerative 

Organism: Human  Tissue;cell: Neuroblastoma  Preparation: Intact cells 

Regulation: Calcium  Coupling state: ROUTINE 

HRR: Oxygraph-2k