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Oxidative stress alters the morphology and toxicity of aortic medial amyloid

DOI: 10.1016/j.bpj.2015.10.034 DOI Help

Authors: Hannah A. Davies (University of Liverpool) , Marie M. Phelan (University of Liverpool) , Mark C. Wilkinson (University of Liverpool) , Raymond  Migrino (Phoenix Veterans Affairs Health Care System) , Seth Truran (Phoenix Veterans Affairs Health Care System) , Daniel Franco (University of Liverpool) , Lu-Ning Liu (University of Liverpool) , Christopher J. Longmore (University of Liverpool) , Jillian Madine (University of Liverpool)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Biophysical Journal , VOL 109 (11) , PAGES 2363 - 2370

State: Published (Approved)
Published: December 2015
Diamond Proposal Number(s): 8979

Open Access Open Access

Abstract: 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

Diamond Keywords: Cardiovascular Disease

Subject Areas: Biology and Bio-materials

Instruments: B23-Circular Dichroism

Added On: 10/12/2015 14:36


Discipline Tags:

Non-Communicable Diseases Health & Wellbeing Biophysics Life Sciences & Biotech

Technical Tags:

Spectroscopy Circular Dichroism (CD)