Detection of oxidized and glycated proteins in clinical samples using mass spectrometry — A user's perspective |
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Authors: | Paul J. Thornalley Naila Rabbani |
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Affiliation: | 1. Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, University Hospital, Coventry CV2 2DX, UK;2. Warwick Systems Biology Centre, Coventry House, University of Warwick, Coventry CV4 7AL, UK |
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Abstract: | BackgroundProteins in human tissues and body fluids continually undergo spontaneous oxidation and glycation reactions forming low levels of oxidation and glycation adduct residues. Proteolysis of oxidised and glycated proteins releases oxidised and glycated amino acids which, if they cannot be repaired, are excreted in urine.Scope of ReviewIn this review we give a brief background to the classification, formation and processing of oxidised and glycated proteins in the clinical setting. We then describe the application of stable isotopic dilution analysis liquid chromatography-tandem mass spectrometry (LC-MS/MS) for measurement of oxidative and glycation damage to proteins in clinical studies, sources of error in pre-analytic processing, corroboration with other techniques – including how this may be improved – and a systems approach to protein damage analysis for improved surety of analyte estimations.Major conclusionsStable isotopic dilution analysis LC-MS/MS provides a robust reference method for measurement of protein oxidation and glycation adducts. Optimised pre-analytic processing of samples and LC-MS/MS analysis procedures are required to achieve this.General significanceQuantitative measurement of protein oxidation and glycation adducts provides information on level of exposure to potentially damaging protein modifications, protein inactivation in ageing and disease, metabolic control, protein turnover, renal function and other aspects of body function. Reliable and clinically assessable analysis is required for translation of measurement to clinical diagnostic use. Stable isotopic dilution analysis LC-MS/MS provides a “gold standard” approach and reference methodology to which other higher throughput methods such as immunoassay and indirect methods are preferably corroborated by researchers and those commercialising diagnostic kits and reagents. This article is part of a Special Issue entitled Current methods to study reactive oxygen species - pros and cons and biophysics of membrane proteins. Guest Editor: Christine Winterbourn. |
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Keywords: | AASA, aminoadipic semialdehyde AGE, advanced glycation endproduct AOPP, advanced oxidation protein product AQC, 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate BUL, bilateral ureteral ligation BNX, bilateral nephrectomy CEL, Nε-(1-carboxyethyl)lysine CML, Nε-carboxymethyl-lysine CRF, chronic renal failure 3DG-H, 3DG-H1 (Nδ-[5-(2,3,4-trihydroxybutyl)-5-hydro-4-imidazolon-2-yl]ornithine) and related structural isomers 3DG-H2 and 3DG-H3 see [1] ESI, electrospray ionisation FCR, fractional clearance rate FL, Nε-fructosyl-lysine GSA, glutamic semialdehyde FN3K, fructosamine-3-kinase FN3KRP, fructosamine-3-kinase related protein G-H1, Nδ-(5-hydro-4-imidazolon-2-yl)ornithine GOLD, glyoxal-derived lysine dimer, 1,3-di(Nε-lysino)imidazolium salt HD, hemodialysis LC-MS/MS, liquid chromatography-tandem mass spectrometry LDL, low density lipoprotein MALDI, matrix assisted laser desorption ionisation MetSO, methionine sulfoxide MG, methylglyoxal MG-H1, Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)ornithine MOLD, methylglyoxal-derived lysine dimer, 1,3-di(Nε-lysino)-4-methyl-imidazolium salt MRM, multiple reaction monitoring MSR, methionine sulfoxide reductase NFK, N-formylkynurenine 3-NT, 3-nitrotyrosine PD, peritoneal dialysis SAF, skin autofluorescence TFA, trifluoroacetic acid UPLC, ultra high performance liquid chromatography |
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