In vitro apolipoprotein E protects human red blood cells against lysis induced by amyloid-beta (AP) fragment 25-35.
Mattson et al. (9) demonstrated lysis of human red blood cells (RBC) exposed to amyloid peptide Abeta(25-35), a new experimental model for amyloid-beta toxicity. Lysis resulted from poreformation in the RBC membranes and was completely prevented by concurrent exposure to Congo red We demonstrate that human serum, purified ApoE from human plasma, and recombinant isoforms of ApoE neutralize the Abeta(25-35) cytotoxicity: the E2 and E4 isoforms were marginally more effective than E3. Second, we demonstrate that Abeta(25-35) forms fibrils in the reaction mixtures using electron-microscopy. Together these results suggest that the RBC model might be useful in preliminary identification of natural and synthetic substances able to protect against amyloid-beta cytotoxic effects due to fibrillar Abeta(25-35). Such compounds would be candidate molecules for testing in neuronal systems.
Galeazzi
Luciano
L
Laboratorio Analisi Chimico-Cliniche, Microbiologiche e di Diagnostica Molecolare, INRCA (IRCSS), Ancona, Italy.
Corder
Elizabeth H
EH
Galeazz
Roberta
R
Casoli
Tiziana
T
Valli
M Beatrice
MB
Giunta
Sergio
S
D000328:Adult; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000502:physiology*; D002478:Cells, Cultured; D003224:Congo Red; D004591:Electrophoresis, Polyacrylamide Gel; D004910:Erythrocyte Membrane / Q000187:drug effects; D004912:Erythrocytes / Q000502:physiology*; D006461:Hemolysis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D010446:Peptide Fragments / Q000633:toxicity*; D011994:Recombinant Proteins
D016229:Amyloid beta-Peptides; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D010446:Peptide Fragments; D011994:Recombinant Proteins; C074636:amyloid beta-protein (25-35); D003224:Congo Red