Amyloid beta-peptides increase annular and bulk fluidity and induce lipid peroxidation in brain synaptic plasma membranes.
Amyloid beta-peptides (A beta) may alter the neuronal membrane lipid environment by changing fluidity and inducing free radical lipid peroxidation. The effects of A beta(1-40) and A beta(25-35) on the fluidity of lipids adjacent to proteins (annular fluidity), bulk lipid fluidity, and lipid peroxidation were determined in rat synaptic plasma membranes (SPM). A fluorescent method based on radiationless energy transfer from tryptophan of SPM proteins to pyrene and pyrene monomer-eximer formation was used to determine SPM annular fluidity and bulk fluidity, respectively. Lipid peroxidation was determined by the thiobarbituric acid assay. Annular fluidity and bulk fluidity of SPM were increased significantly (p < or = 0.02) by A beta(1-40). Similar effects on fluidity were observed for A beta(25-35) (P < or = 0.002). Increased fluidity was associated with lipid peroxidation. Both A beta peptides significantly increased (p < or = 0.006) the amount of malondialdehyde in SPM. The addition of a water-soluble analogue of vitamin E (Trolox) inhibited effects of A beta on lipid peroxidation and fluidity in SPM. The fluidizing action of A beta peptides on SPM may be due to the induction of lipid peroxidation by those peptides. A beta-induced changes in neuronal function, such as ion flux and enzyme activity, that have been reported previously may result from the combined effects of lipid peroxidation and increased membrane fluidity.
Avdulov
N A
NA
VA Medical Center, Department of Pharmacology, University of Minnesota School of Medicine, Minnneapolis, U.S.A.
Chochina
S V
SV
Igbavboa
U
U
O'Hare
E O
EO
Schroeder
F
F
Cleary
J P
JP
Wood
W G
WG
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D004161:Diphenylhexatriene; D005453:Fluorescence; D005456:Fluorescent Dyes; D008054:Lipid Peroxides / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008560:Membrane Fluidity / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D005456:Fluorescent Dyes; D008054:Lipid Peroxides; D010446:Peptide Fragments; D004161:Diphenylhexatriene; D008315:Malondialdehyde