Difference between revisions of "Boyle 2012 Brain Res"
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{{Publication | {{Publication | ||
|title=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 | |title=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. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/22297172 PMID: 22297172] | |info=[http://www.ncbi.nlm.nih.gov/pubmed/22297172 PMID: 22297172] | ||
|authors=Boyle JP, Hettiarachchi NT, Wilkinson JA, Pearson HA, Scragg JL, Lendon C, Al-Owais MM, Kim CB, Myers DM, Warburton P, Peers C | |authors=Boyle JP, Hettiarachchi NT, Wilkinson JA, Pearson HA, Scragg JL, Lendon C, Al-Owais MM, Kim CB, Myers DM, Warburton P, Peers C | ||
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|journal=Brain Res | |journal=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<sup>2+</sup> concentrations in PS1 mutants were never lower than controls and prolonged incubation in Ca<sup>2+</sup>-free solutions did not deplete Ca<sup>2+</sup> stores, demonstrating there was no difference in Ca<sup>2+</sup> leak from endoplasmic reticulum (ER) stores in PS1 mutants. Peak muscarine-evoked rises of [Ca<sup>2+</sup>](i) were variable, but the integrals were not significantly different, suggesting, while kinetics of Ca<sup>2+</sup> store release might be affected in PS1 mutants, store size was similar. However, when Ca<sup>2+</sup>-ATPase activity was irreversibly inhibited with thapsigargin, the S170F and ΔE9 cells showed larger capacitative calcium entry indicating a direct effect on Ca<sup>2+</sup> 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 Ca<sup>2+</sup> stores, is likely to explain the extreme pathology of this mutant. | |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<sup>2+</sup> concentrations in PS1 mutants were never lower than controls and prolonged incubation in Ca<sup>2+</sup>-free solutions did not deplete Ca<sup>2+</sup> stores, demonstrating there was no difference in Ca<sup>2+</sup> leak from endoplasmic reticulum (ER) stores in PS1 mutants. Peak muscarine-evoked rises of [Ca<sup>2+</sup>](i) were variable, but the integrals were not significantly different, suggesting, while kinetics of Ca<sup>2+</sup> store release might be affected in PS1 mutants, store size was similar. However, when Ca<sup>2+</sup>-ATPase activity was irreversibly inhibited with thapsigargin, the S170F and ΔE9 cells showed larger capacitative calcium entry indicating a direct effect on Ca<sup>2+</sup> 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 Ca<sup>2+</sup> stores, is likely to explain the extreme pathology of this mutant. | ||
|keywords=Alzheimer's disease | |keywords=Alzheimer's disease, Presenilin 1 (PS1), Amyloid β Aβ(1-40) and Aβ(1-42), Endoplasmic reticulum | ||
|mipnetlab=UK Leeds Peers C | |mipnetlab=UK Leeds Peers C | ||
}} | }} | ||
{{Labeling | {{Labeling | ||
|area=Respiration, nDNA;cell genetics, mt-Medicine | |||
|diseases=Aging;senescence, Alzheimer's, Neurodegenerative | |||
|organism=Human | |||
|tissues=Neuroblastoma | |||
|preparations=Intact cells | |||
|topics=Calcium | |||
|couplingstates=ROUTINE | |||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
}} | }} | ||
Latest revision as of 13:26, 10 March 2020
| 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 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
