Carbonylated Plasma Proteins
As Potential Biomarkers
of Obesity Induced Type 2 Diabetes Mellitus
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Abstract
Protein
carbonylation is a common nonenzymatic oxidative post-translational
modification, which is often considered as biomarker of oxidative
stress. Recent evidence links protein carbonylation also to obesity
and type 2 diabetes mellitus (T2DM), though the protein targets of
carbonylation in human plasma have not been identified. In this study,
we profiled carbonylated proteins in plasma samples obtained from
lean individuals and obese patients with or without T2DM. The plasma
samples were digested with trypsin, carbonyl groups were derivatized
with O-(biotinylcarbazoylmethyl)hydroxylamine, enriched by avidin
affinity chromatography, and analyzed by RPC-MS/MS. Signals of potentially
modified peptides were targeted in a second LC-MS/MS analysis to retrieve
the peptide sequence and the modified residues. A total of 158 unique
carbonylated proteins were identified, of which 52 were detected in
plasma samples of all three groups. Interestingly, 36 carbonylated
proteins were detected only in obese patients with T2DM, whereas 18
were detected in both nondiabetic groups. The carbonylated proteins
originated mostly from liver, plasma, platelet, and endothelium. Functionally,
they were mainly involved in cell adhesion, signaling, angiogenesis,
and cytoskeletal remodeling. Among the identified carbonylated proteins
were several candidates, such as VEGFR-2, MMP-1, argin, MKK4, and
compliment C5, already connected before to diabetes, obesity and metabolic
diseases