Amyloid β-peptides inhibit Na/K-ATPase: tissue slices versus primary cultures
| Autor: | C. P. Smith, A. Giovanni, G. M. Bores, F Wirtz-Brugger |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
medicine.medical_specialty
chemistry.chemical_element Calcium Hippocampal formation Biology Hippocampus Ouabain Rats Sprague-Dawley chemistry.chemical_compound Culture Techniques Lactate dehydrogenase Internal medicine mental disorders Extracellular medicine Animals Enzyme Inhibitors Na+/K+-ATPase Cells Cultured Cerebral Cortex Neurotransmitter Agents Amyloid beta-Peptides Cell Death L-Lactate Dehydrogenase General Neuroscience Molecular biology Rats Kinetics Endocrinology chemistry Cell culture Sodium-Potassium-Exchanging ATPase medicine.drug Homogenization (biology) |
| Zdroj: | Brain Research Bulletin. 46:423-427 |
| ISSN: | 0361-9230 |
| DOI: | 10.1016/s0361-9230(97)00382-1 |
| Popis: | Abeta1-40 (20 microM) has been reported to selectively inhibit Na+/K+-ATPase activity in rat primary hippocampal cultures after 2-6 days of exposure. We expanded these studies to include Abeta's effects on Na+/K+-ATPase activity in rat primary cortical cultures and hippocampal slices, and we correlated these effects with estimates of cell survival in rat brain primary cultures. Using optimized assay conditions, a 5-day exposure to 50 microM Abeta 25-35, 20 microM Abeta 1-40, and 20 microM Abeta 1-42 decreased Na+/K+-ATPase activity in rat primary cortical cultures 66%, 60%, and 22%, respectively. Abeta 25-35 (50 microM) at 24 h was the only condition that caused inhibition of Na+/K+-ATPase activity in the absence of cell death, defined as an extracellular shift in the localization of the cytoplasmic enzyme lactate dehydrogenase (LDH). We also found that hippocampal slices were sensitive to Abeta, exhibiting a 40-60% reduction in membrane Na+/K+-ATPase activity when exposed to 1-30 nM of Abeta 1-40 for 60 min. This inhibition was not readily reversible, as it withstood homogenization and repeated dilution and centrifugation. Additionally, this inhibition occurred only after amyloid incubation with intact hippocampal slices, not with disrupted membranes. The inhibition of Na+/K+-ATPase in brain slices by physiological, low nM concentrations of Abeta 1-40 is consistent with effects on neurotransmitter release and intrasynaptosomal calcium responses. |
| Databáze: | OpenAIRE |
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