ALZHEIMER'S AMYLOID BETA AFFECTS PHOSPHOLIPID SYNTHESIS IN PC12 AND RAT PRIMARY NEURONALCELL CULTURES
N.V. Koudinova1,2 and E. Yavin1
1. Weizmann Institute of Science, Department of Neurobiology, Rehovot 76100, Israel
2. Russian Academy of Medical Sciences, Institute of Biomedical Chemistry, Timoshenko 38-27, Moscow 121359, Russian Federation
Although amyloid b (Ab) is a major constituent of Alzheimer's (AD) brain amyloid, it is a normal soluble protein (sAb) of plasma and cerebrospinal fluid (CSF). We showed previously that sAb protein is associated with high density lipoproteins in both normal human plasma and CSF, suggesting that sAb is involved in lipid metabolism, as many other protein constituents of lipoproteins do. We also reported (FASEB J (1998) 12, 1097-99) that in HepG2 hepatoma cell line, peptide Ab1-40 decreased synthesis of various lipids, including cholesterol (CHL) and phospholipids (PL), affected in the AD brain. To elucidate whether Ab is capable to regulate the PL and CHL brain synthesis, we studied the peptide effect on the [14C]-acetate incorporation into the newly synthesized PL and CHL of the PC12 and primary neuronal cell cultures. Cells were treated with 1.0 to 500 ng/ml of Ab1-40. In both cell cultures Ab did not change statistically significant the incorporation of [14C]-acetate into CHL and phosphatidylethanolamine (PE). In contrast, the synthesis of sphingomyelin (SPH), phosphatidylserine (PS) and phosphatidylcholine (PC) were increased. In primary neuronal cell cultures synthesis of PS and SPH reached maximum of 30-40% above the control values at Ab concentration of 100-500 ng/ml. In PC12 cells, the lower concentration of the peptide (10-100 ng/ml) saturated the synthesis of PS and PC at 50-70% above 100 % control values. Our data suggest that i) Ab protein regulates physiological neuronal phospholipid biosynthesis, and that ii) this regulation may have Alzheimer's pathological relevance, particularly at high peptide concentration.
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