AMYLOID BETA-INDUCED NEUROTOXICITY IS ASSOCIATED WITH PHOSPHOLIPASE-DACTIVATION IN CULTURED RAT HIPPOCAMPAL CELLS

The role of phopholipase D (PLD) in amyloid beta (A beta)-induced neur otoxicity was studied by comparing the effects of A beta (1-40) on PLD activity and release of lactate dehydrogenase (LDH) from cultured rat hippocampal cells. PLD activity was determined in [H-3]myristic acid- labeled cells by measuring the formation of [H-3]phosphatidylethanol i n the presence of ethanol (0.5%), and LDH activity in the cell media w as measured via colorimetric assay. A beta (50 mu M), aged for 3 days to allow for peptide aggregation, acutely (I h) stimulated PLD activit y. Unaged A beta (50 mu M) had no acute (1 h) effect on PLD activity, but significantly stimulated PLD activity by 87% when incubated with c ells for 1-3 days. A beta (50 mu M)-induced PLD activity was closely c orrelated with AP (50 mu M)-induced LDH release over a time course of 1-3 days. These data suggest that PLD activation may be involved in A beta-induced neurotoxicity. (C) 1997 Elsevier Science Ireland Ltd.