Detection of oxidized and glycated proteins in clinical samples using mass spectrometry — A user's perspective

• Published in: Biochimica et biophysica acta Vol. 1840; no. 2; pp. 818 - 829
• Main Authors: Thornalley, Paul J., Rabbani, Naila
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.02.2014
• Subjects: amino acids; analytical kits; biophysics; body fluids; clinical trials; Dicarbonyl stress; glycation; Glycation End Products, Advanced - analysis; Glycation End Products, Advanced - chemistry; Humans; immunoassays; liquid chromatography; Mass spectrometry; Mass Spectrometry - methods; membrane proteins; Methylglyoxal; oxidation; Oxidation-Reduction; Oxidative stress; Protein glycation; protein metabolism; Protein oxidation; Proteins - analysis; Proteins - chemistry; proteolysis; reactive oxygen species; renal function; tandem mass spectrometry; tissues; GOLD; Oxidative stress; FL; MRM; BNX; TFA; G-H1; LC-MS/MS; NFK; AQC; Dicarbonyl stress; GSA; LDL; BUL; ESI; MG; AGE; 3DG-H; FN3K; MG-H1; CML; MALDI; FN3KRP; CEL; MSR; Protein glycation; AASA; AOPP; Methylglyoxal; Protein oxidation; FCR; MetSO; PD; UPLC; CRF; 3-NT; SAF; HD; Mass spectrometry; MOLD; N(δ)-(5-hydro-4-imidazolon-2-yl)ornithine; low density lipoprotein; methionine sulfoxide reductase; chronic renal failure; bilateral nephrectomy; 3-nitrotyrosine; electrospray ionisation; glutamic semialdehyde; skin autofluorescence; multiple reaction monitoring; N(ε)-carboxymethyl-lysine; methylglyoxal-derived lysine dimer, 1,3-di(N(ε)-lysino)-4-methyl-imidazolium salt; ultra high performance liquid chromatography; glyoxal-derived lysine dimer, 1,3-di(N(ε)-lysino)imidazolium salt; methionine sulfoxide; fractional clearance rate; peritoneal dialysis; fructosamine-3-kinase; N(δ)-(5-hydro-5-methyl-4-imidazolon-2-yl)ornithine; bilateral ureteral ligation; fructosamine-3-kinase related protein; 3DG-H1 (N(δ)-[5-(2,3,4-trihydroxybutyl)-5-hydro-4-imidazolon-2-yl]ornithine) and related structural isomers 3DG-H2 and 3DG-H3 see; N(ε)-fructosyl-lysine; 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate; Nε-(1-carboxyethyl)lysine; N-formylkynurenine; trifluoroacetic acid; advanced oxidation protein product; matrix assisted laser desorption ionisation; hemodialysis; liquid chromatography-tandem mass spectrometry; advanced glycation endproduct; aminoadipic semialdehyde
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2013.03.025

Proteins 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. In 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. Stable 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. Quantitative 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. •Proteins of tissue and body fluids have low level oxidation and glycation adducts.•Cellular proteolysis releases glycated and oxidized amino acids which are then excreted.•Robust adduct measurement is made by stable isotopic dilution analysis LC-MS/MS.•Adduct levels relate to protein turnover, health status, renal function and aging.•A systems biology modelling approach to protein oxidation and glycation is given.