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

Citation

Subasinghe, S and Unabia, S and Barrow, CJ and Mok, SS and Aguilar, MI and Small, DH, Cholesterol is necessary both for the toxic effect of Aβ peptides on vascular smooth muscle cells and for Aβ binding to vascular smooth muscle cell membranes, Journal of Neurochemistry, 84, (3) pp. 471-479. ISSN 0022-3042 (2003) [Refereed Article]

DOI: doi:10.1046/j.1471-4159.2003.01552.x

Abstract

Accumulation of beta amyloid (A) in the brain is central to the pathogenesis of Alzheimer's disease. A 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 A binding to membranes. A peptides bound to synthetic lipid mixtures and to an intact plasma membrane preparation isolated from vascular smooth muscle cells. A peptides were also toxic to vascular smooth muscle cells. There was a good correlation between the toxic effect of A peptides and their membrane binding. 'Ageing' the A 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 A 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 A to purified plasma membrane preparations but also reduced A toxicity. The results support the view that A 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 A-membrane binding.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Neurosciences not elsewhere classified
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Neurodegenerative Disorders Related to Ageing
Author:Small, DH (Professor David Small)
ID Code:63306
Year Published:2003
Web of Science® Times Cited:75
Deposited By:Menzies Institute for Medical Research
Deposited On:2010-04-28
Last Modified:2010-09-16
Downloads:0

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