Amyloid beta but not bradykinin induces phosphatidylcholine hydrolysis in immortalized rat brain endothelial cells.

We describe the inhibitory effect of A beta (25-35) fragment of amyloid-beta peptide and bradykinin (BK) on phosphatidylcholine (PtdCho) metabolism in immortalized rat brain GP8.39 endothelial cells (EC). Cultures were incubated either with A beta for 24-48 h, or with BK for 30 min-4 h. The peroxidation indices (malondialdehyde, conjugated dienes) and lactate dehydrogenase (LDH) release significantly increased after A beta peptide (10-50 microM) treatment. The BK (10 microM) stimulation of cells brought about an increase in conjugated dienes and LDH release only after 4 h. Following 24 h treatment with 50 microM A beta peptide, the [Me-3H]choline incorporation into PtdCho strongly decreased while the [3H]choline release increased, indicating PtdCho hydrolysis. The effect was most likely due to peptide prooxidant effect. After 4 h preincubation with BK, the [Me-3H]choline incorporation into PtdCho strongly decreased, but no significant [3H]choline release was found. Following long-term treatment, the action of 50 microM A beta on [3H]choline release was not enhanced by 10 microM BK. Cell exposure to alpha-tocopherol (1 mM) prior to the addition of both agents did not abolish stimulated PtdCho breakdown. The data suggest that: (a) A beta peptide and BK may modulate phospholipid turnover in microvessel cells; (b) they could not synergistically interact in vascular EC damage during processes involving amyloid accumulation and inflammatory response.