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The β-amyloid peptide of Alzheimer's disease decreases adhesion of vascular smooth muscle cells to the basement membrane

Citation

Mok, SS and Losic, D and Barrow, CJ and Turner, BJ and Masters, CL and Martin, LL and Small, DH, The β-amyloid peptide of Alzheimer's disease decreases adhesion of vascular smooth muscle cells to the basement membrane, Journal of Neurochemistry, 96, (1) pp. 53-64. ISSN 0022-3042 (2006) [Refereed Article]

DOI: doi:10.1111/j.1471-4159.2005.03539.x

Abstract

Cerebral amyloid angiopathy (CAA) is a major feature of Alzheimer's disease pathology. In CAA, degeneration of vascular smooth muscle cells (VSMCs) occurs close to regions of the basement membrane where the amyloid protein (A) builds up. In this study, the possibility that A disrupts adhesive interactions between VSMCs and the basement membrane was examined. VSMCs were cultured on a commercial basement membrane substrate (Matrigel). The presence of A in the Matrigel decreased cell-substrate adhesion and cell viability. Full-length oligomeric A was required for the effect, as N- and C-terminally truncated peptide analogues did not inhibit adhesion. A that was fluorescently labelled at the N-terminus (fluo-A) bound to Matrigel as well as to the basement membrane heparan sulfate proteoglycan (HSPG) perlecan and laminin. Adhesion of VSMCs to perlecan or laminin was decreased by A. As perlecan influences VSMC viability through the extracellular signal-regulated kinase (ERK)1/2 signalling pathway, the effect of A1-40 on ERK1/2 phosphorylation was examined. The level of phospho-ERK1/2 was decreased in cells following A treatment. An inhibitor of ERK1/2 phosphorylation enhanced the effect of A on cell adhesion. The studies suggest that A can decrease VSMC viability by disrupting VSMC-extracellular matrix (ECM) adhesion.

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:61096
Year Published:2006
Web of Science® Times Cited:22
Deposited By:Menzies Institute for Medical Research
Deposited On:2010-02-25
Last Modified:2010-09-16
Downloads:0

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