Amyloid β(1-42) and its β(25-35) fragment induce in vitro phosphatidylcholine hydrolysis in bovine retina capillary pericytes

We describe the inhibitory effect of full-length A beta (1-42) and A beta (25-35) fragment of amyloid-beta peptide on phosphatidylcholine (PtdCho) metabolism in bovine retina capillary pericytes. Cell cultures were incubated with A betas for 24 h. Peroxidation indices (malondialdehyde and lactate dehydrogenase release) significantly increased after 20-50 muM A beta (1-42) or A beta (25-35) treatment. in addition, [Me-H-3]choline incorporation into PtdCho strongly decreased while either H-3-choline or C-14-arachidonic acid release from prelabeled cells increased, indicating PtdCho hydrolysis. The effect was very likely due to prooxidant action of both A beta peptides. Reversed-sequence A beta (35-25) peptide did not depress H-3-choline incorporation nor stimulate PtdCho breakdown. With addition of A betas at low concentrations (2-20 muM) to pericytes, marked ultrastructural changes, well connected to metabolic alterations, emerged including shrinkage of cell bodies, retraction of processes, disruption of the intracellular actin network. Cells treated with higher concentrations (50-200 muM) displayed characteristics of necrotic cell death. The data suggest that: (a) A beta (1-42) and A beta (25-35) peptides may modulate phospholipid turnover in microvessel pericytes; (b) together with endothelial cells, pericytes could be the target of vascular damage during processes involving amyloid accumulation. (C) 2001 Published by Elsevier Science Ireland Ltd.