Oxidative Stress Alters the Morphology and Toxicity of Aortic Medial Amyloid

Davies, Hannah, Phelan, Marie, Wilkinson, Mark, Migrino, Raymond, Truran, Seth, Franco, Daniel A, Liu, Luning ORCID: 0000-0002-8884-4819, Longmore, Christopher and Madine, Jill ORCID: 0000-0001-9963-5871
(2015) Oxidative Stress Alters the Morphology and Toxicity of Aortic Medial Amyloid. Biophysical Journal, 109 (11). pp. 2363-2370.

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The aggregation and fibril deposition of amyloid proteins have been implicated in a range of neurodegenerative and vascular diseases, and yet the underlying molecular mechanisms are poorly understood. Here, we use a combination of cell-based assays, biophysical analysis, and atomic force microscopy to investigate the potential involvement of oxidative stress in aortic medial amyloid (AMA) pathogenesis and deposition. We show that medin, the main constituent of AMA, can induce an environment rich in oxidative species, increasing superoxide and reducing bioavailable nitric oxide in human cells. We investigate the role that this oxidative environment may play in altering the aggregation process of medin and identify potential posttranslational modification sites where site-specific modification and interaction can be unambiguously demonstrated. In an oxidizing environment, medin is nitrated at tyrosine and tryptophan residues, with resultant effects on morphology that lead to longer fibrils with increased toxicity. This provides further motivation to investigate the role of oxidative stress in AMA pathogenicity.

Item Type: Article
Uncontrolled Keywords: Aorta, Humans, Nitrates, Milk Proteins, Antigens, Surface, Oxidative Stress, Human Umbilical Vein Endothelial Cells
Subjects: ?? QH301 ??
Depositing User: Symplectic Admin
Date Deposited: 15 Dec 2015 10:04
Last Modified: 15 Mar 2024 05:00
DOI: 10.1016/j.bpj.2015.10.034
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/2042879