Amyloid beta(1-42) and its beta(25-35) fragment induce in vitro phosphatidylcholine hydrolysis in bovine retina capillary pericytes.
We describe the inhibitory effect of full-length Abeta(1-42) and Abeta(25-35) fragment of amyloid-beta peptide on phosphatidylcholine (PtdCho) metabolism in bovine retina capillary pericytes. Cell cultures were incubated with Abetas for 24 h. Peroxidation indices (malondialdehyde and lactate dehydrogenase release) significantly increased after 20-50 microM Abeta(1-42) or Abeta(25-35) treatment. In addition, [Me-3H]choline incorporation into PtdCho strongly decreased while either 3H-choline or 14C-arachidonic acid release from prelabeled cells increased, indicating PtdCho hydrolysis. The effect was very likely due to prooxidant action of both Abeta peptides. Reversed-sequence Abeta(35-25) peptide did not depress 3H-choline incorporation nor stimulate PtdCho breakdown. With addition of Abetas at low concentrations (2-20 microM) 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 microM) displayed characteristics of necrotic cell death. The data suggest that: (a) Abeta(1-42) and Abeta(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.
Lupo
G
G
Department of Biochemistry, Faculty of Medicine, University of Catania, Viale A. Doria 6, 95125, Catania, Italy.
Anfuso
C D
CD
Assero
G
G
Strosznajder
R P
RP
Walski
M
M
Pluta
R
R
Alberghina
M
M
D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid / Q000493:pharmacokinetics; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology; D002196:Capillaries / Q000187:drug effects* / Q000503:physiopathology / Q000648:ultrastructure; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D002417:Cattle; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D002794:Choline / Q000493:pharmacokinetics; D006868:Hydrolysis / Q000187:drug effects; D008854:Microscopy, Electron; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D020286:Pericytes / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D010713:Phosphatidylcholines / Q000378:metabolism*; D012161:Retinal Artery / Q000187:drug effects* / Q000503:physiopathology / Q000648:ultrastructure; D014316:Tritium / Q000493:pharmacokinetics
D016229:Amyloid beta-Peptides; D002250:Carbon Radioisotopes; D010446:Peptide Fragments; D010713:Phosphatidylcholines; C113041:amyloid beta-protein (35-25); D014316:Tritium; D016718:Arachidonic Acid; D002794:Choline