Role of oxidative stress in physiological albumin glycation: a neglected interaction

Vlassopoulos, A., Lean, M.E.J. and Combet, E. (2013) Role of oxidative stress in physiological albumin glycation: a neglected interaction. Free Radical Biology and Medicine, 60, pp. 318-324. (doi:10.1016/j.freeradbiomed.2013.03.010)

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Abstract

Protein glycation is a key mechanism involved in chronic disease development in both diabetic and nondiabetic individuals. About 12–18% of circulating proteins are glycated in vivo in normoglycemic blood, but in vitro studies have hitherto failed to demonstrate glucose-driven glycation below a concentration of 30 mM. Bovine serum albumin (BSA), reduced BSA (mercaptalbumin) (both 40 g/L), and human plasma were incubated with glucose concentrations of 0–30 mM for 4 weeks at 37 °C. All were tested preoxidized for 8 h before glycation with 10 nM H2O2 or continuously exposed to 10 nM H2O2 throughout the incubation period. Fructosamine was measured (nitroblue tetrazolium method) at 2 and 4 weeks. Oxidized BSA (both preoxidized and continuously exposed to H2O2) was more readily glycated than native BSA at all glucose concentrations (p = 0.03). Moreover, only oxidized BSA was glycated at physiological glucose concentration (5 mM) compared to glucose-free control (glycation increased by 35% compared to native albumin, p < 0.05). Both 5 and 10 mM glucose led to higher glycation when mercaptalbumin was oxidized than when unoxidized (p < 0.05). Fructosamine concentration in human plasma was also significantly higher when oxidized and exposed to 5 mM glucose, compared to unoxidized plasma (p = 0.03). The interaction between glucose concentration and oxidation was significant in all protein models (p < 0.05). This study has for the first time demonstrated albumin glycation in vitro, using physiological concentrations of albumin, glucose, and hydrogen peroxide, identifying low-grade oxidative stress as a key element early in the glycation process.

Item Type:Articles
Additional Information:NOTICE: this is the author’s version of a work that was accepted for publication in Free Radical Biology and Medicine. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Free Radical Biology and Medicine, 60, 2013. http://dx.doi.org/10.1016/j.freeradbiomed.2013.03.010
Keywords:Oxidative stress; hydrogen peroxide; albumin; plasma; glucose; mercaptalbumin; glycation; glucose; free radicals
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Lean, Professor Michael and Combet Aspray, Dr Emilie
Authors: Vlassopoulos, A., Lean, M.E.J., and Combet, E.
College/School:College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Free Radical Biology and Medicine
Publisher:Elsevier
ISSN:0891-5849
ISSN (Online):1873-4596
Published Online:18 March 2013
Copyright Holders:Copyright © 2013 Elsevier Ltd.
First Published:First published in Free Radical Biology and Medicine 60:318-324
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
557722Dietary intervention in obese pregnancies: impact on glycation, inflammation and newborn adiposityEmilie Combet AsprayYorkhill Children's Foundation (YORKH-CHIL)UNSPECIFIEDMVLS MED -HUMAN NUTRITION