Suppression of an amyloid β-peptidemediated calcium channel response by a secreted β-amyloid precursor protein
Autor: | Dan L. Czilli, J.P Butler, John E. Hale, Sheila P. Little, Mcclure Don B, Weiying Li, L.K Simmons |
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Rok vydání: | 1999 |
Předmět: |
Patch-Clamp Techniques
Amyloid beta chemistry.chemical_element Calcium Biology Hippocampus Calcium in biology Amyloid beta-Protein Precursor mental disorders Amyloid precursor protein Animals Cyclic GMP Cells Cultured Amyloid beta-Peptides General Neuroscience Calcium channel P3 peptide Peptide Fragments Rats Cell biology Biochemistry of Alzheimer's disease chemistry Biochemistry biology.protein Calcium Channels Amyloid precursor protein secretase |
Zdroj: | Neuroscience. 95:1-4 |
ISSN: | 0306-4522 |
DOI: | 10.1016/s0306-4522(99)00479-0 |
Popis: | Secreted isoforms of the beta-amyloid precursor protein potently enhance neuronal survival in cell cultures exposed to toxic amyloid beta peptide. Lowering of intracellular calcium levels to offset the increases in intraneuronal calcium caused by amyloid beta peptide is thought to underly this neuroprotection. Because we have shown previously that an amyloid beta peptide-mediated potentiation of calcium channel currents may contribute to this cytosolic calcium overload, the present study examined the effects of a secreted beta-amyloid precursor protein on the calcium channel response to amyloid beta peptide. When compared with untreated cultured rat hippocampal neurons, cells that underwent a 24 h preincubation with beta-amyloid precursor protein 751 displayed decreases in the relative size of the calcium channel response to amyloid beta peptide. A membrane-permeable analog of cyclic GMP, a second messenger believed to be involved in the calcium regulation process mediated by beta-amyloid precursor proteins, also attenuated the modulatory calcium channel response. Co-application of beta-amyloid precursor protein 751 with amyloid beta peptide did not alter calcium channel response to amyloid beta peptide. Taken together, these findings suggest that secreted beta-amyloid precursor proteins can suppress a calcium channel response to amyloid beta peptide that is potentially injurious to the cell, and as such, may define a neuroprotective mechanism that is specific for amyloid beta toxicity. |
Databáze: | OpenAIRE |
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