PubMed:22297172 JSONTXT

{"project":"Allie","denotations":[{"id":"SS1_22297172_1_0","span":{"begin":151,"end":163},"obj":"expanded"},{"id":"SS2_22297172_1_0","span":{"begin":165,"end":168},"obj":"abbr"},{"id":"SS1_22297172_3_0","span":{"begin":629,"end":650},"obj":"expanded"},{"id":"SS2_22297172_3_0","span":{"begin":652,"end":654},"obj":"abbr"}],"relations":[{"id":"AE1_22297172_1_0","pred":"abbreviatedTo","subj":"SS1_22297172_1_0","obj":"SS2_22297172_1_0"},{"id":"AE1_22297172_3_0","pred":"abbreviatedTo","subj":"SS1_22297172_3_0","obj":"SS2_22297172_3_0"}],"text":"Cellular consequences of the expression of Alzheimer's disease-causing presenilin 1 mutations in human neuroblastoma (SH-SY5Y) cells.\nMutations 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."}

{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":195,"end":214},"obj":"HP_0002511"},{"id":"T2","span":{"begin":1150,"end":1163},"obj":"HP_0001427"},{"id":"T3","span":{"begin":1177,"end":1184},"obj":"HP_0011034"}],"text":"Cellular consequences of the expression of Alzheimer's disease-causing presenilin 1 mutations in human neuroblastoma (SH-SY5Y) cells.\nMutations 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."}