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.
Anfuso
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Institute of Biochemistry, Faculty of Medicine, University of Catania, Italy.
Lupo
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Alberghina
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D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D001921:Brain / Q000166:cytology; D002461:Cell Line, Transformed / Q000187:drug effects / Q000378:metabolism; D002794:Choline / Q000493:pharmacokinetics; D004727:Endothelium / Q000166:cytology; D005609:Free Radicals / Q000378:metabolism; D006868:Hydrolysis; D010446:Peptide Fragments / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000378:metabolism*; D051381:Rats; D014316:Tritium; D014810:Vitamin E / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D005609:Free Radicals; D010446:Peptide Fragments; D010713:Phosphatidylcholines; C074636:amyloid beta-protein (25-35); D014316:Tritium; D014810:Vitamin E; D002794:Choline; D001920:Bradykinin