A.R. Koudinov1,2; T.T. Berezov1; N.V. Koudinova1,2
1. Russian Academy of Medical Sciences, National Mental Health Research Center, Institute of Biomedical Chemistry, Timoshenko 38-27, Moscow 121359, Russia
2. Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel
Amyloid b (Ab) is a major constituent of Alzheimer's and Down's syndrome brain amyloid and a normal soluble human protein (sAb). We showed previously that sAb in both normal plasma, CSF and hepatic cell culture supernatant is associated with the HDL. These and other facts prompted us to ascertain whether there is a function of Ab peptide related to cholesterol metabolism and whether it affects cellular lipid synthesis. For this purpose we tested the effect of synthetic Ab1-40 and Ab1-28 on plasma cholesterol esterification rate. Both peptides at a physiologic concentration of 1 ng/ml similarly inhibited plasma cholesterol esterification rate to 40-50 % of control value. We also tested the effect of Ab1-40, homologous to the major circulatory and HDL associated species of Alzheimer's sAb, on lipid biosynthesis in human HepG2 hepatoma cells. This culture synthesizes various lipids from [14C]-acetate as a precursor. Treatment of cells with different concentrations of Ab1-40 decreased the syntheses of various radiolabeled lipid species. The decrease reached saturation at the concentration 10 ng of Ab per ml of media. The lipids whose synthesis was decreased most were free and esterified cholesterol and phospholipids (25-40 % maximum inhibition). Synthesis of triacylglycerols was also reduced but to a lower extent. Our data suggest that Ab has extended functions in lipid metabolism. In addition, the observed effects may be of special importance in pathological condition, and contribute to the neurodegeneration, in Alzheimer's disease and related disorders.
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