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- Title
Site-Specific GlcNAcylation of Human Erythrocyte Proteins Potential Biomarker(s) for Diabetes.
- Authors
Wang, Zihao; Park, Kyoungsook; Comer, Frank; Hsieh-Wilson, Linda C.; Saudek, Christopher D.; Hart, Gerald W.
- Abstract
OBJECTIVE--O-linked N-acetylglucosamine (O-GlcNAc) is upregulated in diabetic tissues and plays a role in insulin resistance and glucose toxicity. Here, we investigated the extent of GlcNAcylation on human erythrocyte proteins and compared site-specific GlcNAcylation on erythrocyte proteins from diabetic and normal individuals. RESEARCH DESIGN AND METHODS--GlcNAcylated erythrocyte proteins or GlcNAcylated peptides were tagged and selectively enriched by a chemoenzymatic approach and identified by mass spectrometry. The enrichment approach was combined with solid-phase chemical derivatization and isotopic labeling to detect O-GlcNAc modification sites and to compare site-specific O-GlcNAc occupancy levels between normal and diabetic erythrocyte proteins. RESULTS--The enzymes that catalyze the cycling (addition and removal) of O-GlcNAc were detected in human erythrocytes. Twenty-five GlcNAcylated erythrocyte proteins were identified. Protein expression levels were compared between diabetic and normal erythrocytes. Thirty-five O-GlcNAc sites were reproducibly identified, and their site-specific O-GlcNAc occupancy ratios were calculated. CONCLUSIONS--GlcNAcylation is differentially regulated at individual sites on erythrocyte proteins in response to glycemic status. These data suggest not only that site-specific-GlcNAc levels reflect the glycemic status of an individual but also that O-GlcNAc site occupancy on erythrocyte proteins may be eventually useful as a diagnostic tool for the early detection of diabetes. Diabetes 58:309-317, 2009
- Subjects
GLUCOSAMINE; ERYTHROCYTES; BIOMARKERS; DIABETES; INSULIN resistance
- Publication
Diabetes, 2009, Vol 58, Issue 2, p309
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db08-0994