Glyoxal is the most reactive α-dicarbonyl compound released from glycated proteins. It is also present in the environment and in cigarette smoke. The mutagenic glyoxal reacts with biomolecules, modifying proteins and DNA causing cross-links between them which are implicated in complications associated with hyperglycemia. The plasma concentrations of glyoxal are higher in diabetic patients than in healthy individuals. Using a highly sensitive and specific stable isotope dilution nanoflow liquid chromatography nanospray ionization tandem mass spectrometry, we can accurately quantify glyoxal-induced DNA cross-links in human leukocytes starting from 50 mg DNA isolated from 2-3 mL of blood. Levels of these DNA cross-links are higher in type 2 diabetes mellitus patients than in healthy subjects. On the other hand, the sites and types of glyoxal-induced post-translational modifications on human hemoglobin were characterized using the shot-gun proteomic approach. These glyoxal-modified peptides were semiquantified n hemoglobin isolated from as little as one drop of blood. The extents of modification on certain sites of the peptides were higher in diabetic patients than in healthy individuals. The results suggest the potential use of these glyoxal-induced adducts in blood as feasible biomarker candidates to assess DNA and protein damage in diabetes mellitus.

Analysis of glyoxal-induced DNA and protein damage in blood of diabetic patients by mass spectrometry

254th National Meeting (2017)

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