Increasing Membrane Cholesterol Level Increases the Amyloidogenic Peptide by Enhancing the Expression of Phospholipase C
Figure 6
Suppression of PLCβ1 expression prevented the effects of augmentation of membrane cholesterol levels on PIP2 levels and Aβ42 production. (a, b) The effect of cholesterol on PIP2 levels was blocked in the presence of antisense oligonucleotides directed against PLCβ1. APP-transfected HeLa cells were incubated with or without 75 μM water-soluble cholesterol for 2 h, and PIP2 levels in the membrane fractions were measured by using a PIP2 ELISA kit. In some cells, antisense oligonucleotides directed against PLCβ1 or PLCβ3 (10 μM) were pretreated for 4 h before the cholesterol treatment. The presence of PLCβ1 antisense oligonucleotides (), but not that of PLCβ3, prevented the effects of cholesterol (). (c, d) The effect of cholesterol on Aβ42 production was blocked in the presence of antisense oligonucleotides directed against PLCβ1. After treating cells as in (a) and (b), Aβ42 levels were measured from the conditioned media by using ELISA method. The presence of PLCβ1 antisense oligonucleotides (), but not that of PLCβ3, blocked the effects of cholesterol enrichment (). *; **; ***.
