Purified High Molecular Weight Synthetic Aβ(1-42) and Biological Aβ Oligomers are Equipotent in Rapidly Inducing MTT Formazan Exocytosis

摘要

Synthetic soluble Aβ oligomers are often used as a surrogate for biologic material in a number of model systems. We compared the activity of Aβ oligomers (synthetic and cell culture media derived) on the human SH-SY5Y neuroblastoma and C2C12 mouse myoblast cell lines in a novel, modified MTT assay. Separating oligomers from monomeric peptide by size-exclusion chromatography produced effects at peptide concentrations approaching physiologic levels (10–100 nM). Purified oligomers, but not monomers or fibrils, elicited an increase of a detergent-insoluble form of MTT formazan within two hours as opposed to a control toxin (H2O2). This effect was comparable for biological and synthetic peptide in both cell types. Monomeric Aβ attenuated the effect of soluble oligomers. This study suggests that the activities of biological and synthetic oligomers are indistinguishable during early stages of Aβ oligomer-cell interaction.