Abstract
Oxidative stress has been linked to a number of chronic diseases, and this has aroused interest in the identification of clinical biomarkers that can accurately assess its severity. We used liquid chromatography-high resolution mass spectrometry (LC-MS) to show that oxidised and non-oxidised Met residues at position 147 of human serum albumin (Met147) can be accurately and reproducibly quantified with stable isotope-labelled peptides. Met147 oxidation was significantly higher in patients with diabetes than in controls. Least square multivariate analysis revealed that glycated haemoglobin (HbA1c) and glycated albumin (GA) did not significantly influence Met147 oxidation, but the GA/HbA1c ratio, which reflects glycaemic excursions, independently affected Met147 oxidation status. Continuous glucose monitoring revealed that Met147 oxidation strongly correlates with the standard deviation of sensor glucose concentrations and the time spent with hypoglycaemia or hyperglycaemia each day. Thus, glycaemic variability and hypoglycaemia in diabetes may be associated with greater oxidation of Met147. Renal function, high-density lipoprotein-cholesterol and serum bilirubin were also associated with the oxidation status of Met147. In conclusion, the quantification of oxidised and non-oxidised Met147 in serum albumin using our LC-MS methodology could be used to assess the degree of intravascular oxidative stress induced by hypoglycaemia and glycaemic fluctuations in diabetes.
Highlights
Oxidative stress has been linked to a number of chronic diseases, and this has aroused interest in the identification of clinical biomarkers that can accurately assess its severity
We have quantified the levels of oxidised and non-oxidised Met at position 147 of human serum albumin (Met147), to determine whether the oxidation status of this residue reflects the oxidative stress induced during disease pathophysiology, and whether this might represent a useful biomarker of oxidative stress
We previously found that the ratio of trypsin-digested serum albumin fragments containing oxidised and a non-oxidised Met residues at position 147 of human serum albumin, Alb(Met147O) and Alb(Met147), is one of the most promising potential clinical biomarker of intravascular redox status among the Met-containing tryptic serum proteins identified using a proteomic strategy[28]
Summary
Oxidative stress has been linked to a number of chronic diseases, and this has aroused interest in the identification of clinical biomarkers that can accurately assess its severity. We have recently found that the mass spectral intensity of serum tryptic peptides containing oxidised and non-oxidised Met residues can be very stably and reproducibly measured using liquid chromatography-high resolution mass spectrometry (LC-MS), irrespective of the time the blood sample is left to clot at room temperature before centrifugation or repeated freeze/thaw cycles[28] This may be because of the absence of MetO reductase activity in human blood[29], these have not been well characterised to date. We have quantified the levels of oxidised and non-oxidised Met at position 147 of human serum albumin (Met147), to determine whether the oxidation status of this residue reflects the oxidative stress induced during disease pathophysiology, and whether this might represent a useful biomarker of oxidative stress To this end, we have improved our mass spectrometric methodology for the accurate and stable quantification of such residues in clinically-derived samples
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