Lysophosphatidylcholine increases the neurotoxicity of Alzheimer's amyloid β1-42 peptide: role of oligomer formation
Abstract
Oligomer formation is considered as a critical process for the neurotoxic effects of Alzheimer's amyloid β (Aβ) peptide. Previously we have demonstrated that lysophosphatidylcholine (LPC) increases the oligomer formation of Aβ1-42, the major Aβ peptide found Alzheimer's disease (AD) lesions. In this study, we have investigated whether LPC affects the neurotoxic effects of Aβ1-42 in a neuronal cell line (A1) culture. Dimethyl thiazolyl diphenyl tetrazolium (MTT) assay revealed that up to 10μM concentration, LPC did not affect A1 cell viability. Aβ1-42 decreased the cell viability, and such effect was dose dependently enhanced by LPC. However, neither LPC nor Aβ1-42, alone or in combination increased lactate dehydrogenase (LDH) release from A1 cells after 24-h treatment. Terminal deoxynucleotidyl transferase dUTP-biotin nick-end-labeling (TUNEL) assay showed that LPC increased Aβ1-42-induced apoptotic cell number. To determine the underlying mechanisms, the proteins implicated in apoptosis pathways including Bcl-2- and caspase-family were analyzed by Western blotting. The results demonstrated that Aβ1-42 decreased Bcl-2 in A1 cells at 24h, whereas LPC had no effect at any time point. Both LPC and Aβ1-42 increased Bax level at 24h...Continue Reading
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