Cholesterol is necessary both for the toxic effect of Abeta peptides on vascular smooth muscle cells and for Abeta binding to vascular smooth muscle cell membranes

Subasinghe, Supundi, Unabia, Sharon, Barrow, Colin J., Mok, Su San, Aguilar, Marie-Isabel and Small, David H. 2003, Cholesterol is necessary both for the toxic effect of Abeta peptides on vascular smooth muscle cells and for Abeta binding to vascular smooth muscle cell membranes, Journal of neurochemistry, vol. 84, no. 3, pp. 471-479.

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Title Cholesterol is necessary both for the toxic effect of Abeta peptides on vascular smooth muscle cells and for Abeta binding to vascular smooth muscle cell membranes
Author(s) Subasinghe, Supundi
Unabia, Sharon
Barrow, Colin J.
Mok, Su San
Aguilar, Marie-Isabel
Small, David H.
Journal name Journal of neurochemistry
Volume number 84
Issue number 3
Start page 471
End page 479
Total pages 9
Publisher Wiley-Blackwell
Place of publication Oxford, England
Publication date 2003
ISSN 0022-3042
1471-4159
Summary Accumulation of beta amyloid (Aβ) in the brain is central to the pathogenesis of Alzheimer's disease. Aβ can bind to membrane lipids and this binding may have detrimental effects on cell function. In this study, surface plasmon resonance technology was used to study Aβ binding to membranes. Aβ peptides bound to synthetic lipid mixtures and to an intact plasma membrane preparation isolated from vascular smooth muscle cells. Aβ peptides were also toxic to vascular smooth muscle cells. There was a good correlation between the toxic effect of Aβ peptides and their membrane binding. 'Ageing' the Aβ peptides by incubation for 5 days increased the proportion of oligomeric species, and also increased toxicity and the amount of binding to lipids. The toxicities of various Aβ analogs correlated with their lipid binding. Significantly, binding was influenced by the concentration of cholesterol in the lipid mixture. Reduction of cholesterol in vascular smooth muscle cells not only reduced the binding of Aβ to purified plasma membrane preparations but also reduced Aβ toxicity. The results support the view that Aβ toxicity is a direct consequence of binding to lipids in the membrane. Reduction of membrane cholesterol using cholesterol-lowering drugs may be of therapeutic benefit because it reduces Aβ-membrane binding.
Language eng
Field of Research 110106 Medical Biochemistry: Proteins and Peptides (incl Medical Proteomics)
Socio Economic Objective 970110 Expanding Knowledge in Technology
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2003, Wiley-Blackwell Publishing
Persistent URL http://hdl.handle.net/10536/DRO/DU:30023812

Document type: Journal Article
Collection: School of Life and Environmental Sciences
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