Amyloid beta-induced neurotoxicity is associated with phospholipase D activation in cultured rat hippocampal cells.
The role of phospholipase D (PLD) in amyloid beta (Abeta)-induced neurotoxicity was studied by comparing the effects of Abeta (1-40) on PLD activity and release of lactate dehydrogenase (LDH) from cultured rat hippocampal cells. PLD activity was determined in [3H]myristic acid-labeled cells by measuring the formation of [3H]phosphatidylethanol in the presence of ethanol (0.5%), and LDH activity in the cell media was measured via colorimetric assay. Abeta (50 microM), aged for 3 days to allow for peptide aggregation, acutely (1 h) stimulated PLD activity. Unaged Abeta (50 microM) had no acute (1 h) effect on PLD activity, but significantly stimulated PLD activity by 87% when incubated with cells for 1-3 days. Abeta (50 microM)-induced PLD activity was closely correlated with Abeta (50 microM)-induced LDH release over a time course of 1-3 days. These data suggest that PLD activation may be involved in Abeta-induced neurotoxicity.
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Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 47628, USA.
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D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003124:Colorimetry; D004789:Enzyme Activation; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D009498:Neurotoxins / Q000633:toxicity*; D010739:Phospholipase D / Q000378:metabolism*; D051381:Rats
D016229:Amyloid beta-Peptides; D009498:Neurotoxins; D007770:L-Lactate Dehydrogenase; D010739:Phospholipase D