Apolipoprotein E4 and A beta peptide 1-42 inhibit polyphosphoinositide biosynthesis in rat brain cortex

Polyphosphoinositides synthesized by phosphatidylinositol 4-kinase, EC 2.7.1.67 (PI4K) and phosphatidylinositol 4-phosphate 5-kinase, EC 2.7.1.68 (PIP5K) are involved in cell signaling and cytoskeleton function. In this study, the effect of apolipoprotein E4 (apoE4) and amyloid beta peptide A beta 1-42 on PI4K and PIP5K activity in cortical synaptic plasma membranes from rat brain was investigated. The results indicated that 0.25 microM apoE4 inhibited PI4K and PIP5K by 40% and 30%, respectively, but 25 microM A beta 1-42 decreased exclusively PI4K activity by 20%. Although the mechanism of apoE4 and A beta action is unknown and needs future investigation, this study suggests that free radical-dependent protein oxidation may be involved in alteration of these enzymes.