Choline plus cytidine stimulate phospholipid production, and the expression and secretion of amyloid precursor protein in rat PC12 cells

The amyloid precursor protein (APP) is a transmembrane protein anchored in the membrane lipid bilayer. Choline and cytidine are major precursors of cell membranes, and are regulatory elements in membrane biosynthesis. We examined the levels of cellular APP holoprotein and secreted APPs when rat PC12 cells are stimulated to undergo increase in membrane phospholipids by choline+cytidine (2+2, 5+5, 10+10 or 50+50 μM) treatment. We now show that as phospholipids levels are increased by supplemental choline and cytidine treatment, the levels of cell-associated APP also rise stoichiometrically; these treatments also caused major (up to 6.8-fold) increases in the amounts of secreted APP released into the cell medium, and also stimulated increased process formation. These results show that choline plus cytidine increase both phospholipid levels, and the expression and secretion in PC12 cells. It appears that agents that stimulate cellular membrane biosynthesis may be used to stimulate the secretion of neurotrophic APPs and neurite formation in neurodegenerative disorders such as Alzheimer's disease.