Purpose: Long-term glycemic index in patients with diabetes mellitus (DM) is measured by glycated hemoglobin (HbA1c) besides blood glucose. In DM, the primary amino groups of proteins get glycated via non-enzymatic post-translational modification. This study aims at identifying and characterizing site-specific glycation of erythrocyte proteome across varying glycemic index in patients with DM.
Experiments: We isolated the glycated erythrocyte proteome devoid of hemoglobin from control and diabetic samples using boronate affinity chromatography. Proteomic analysis was performed using nanoLC/ESI-MS proteomics platform. The site-specific modification on different proteins was deciphered using a customized database.
Results: We report 37 glycated proteins identified and characterized from samples with HbA1c of 6%, 8%, 12%, and 16%. Our results show that both extent and site-specific modification of proteins increased with increasing HbA1c. The observed residue-specific modifications of catalase, peroxiredoxin, carbonic anhydrase, lactate dehydrogenase B and delta-aminolevulinic acid dehydratase were correlated with the literature report on their functional disorder in DM.
Conclusions: and clinical relevance: 37 glycated erythrocyte proteins apart from hemoglobin were characterized from DM patient samples with varying HbA1c values. We correlated the site-specific glycation and associated functional disorder of five representative proteins. However, the clinical correlation with the observed modifications needs further investigation.
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