It is generally appreciated that platelets derived from diabetic patients display increased responsiveness to low levels of agonists. O-GlcNAcylation has been linked to hyperglycemia-related effects in other tissues; therefore we examined this modification in platelets to determine if O-GlcNAcylation affects platelet function. This post-translational modification consists of an N-acetylglucosamine attached to serine and/or threonine residues. We examined O-GlcNAc levels in platelets from a hyperglycemic murine model of Type I diabetes with known hypersensitivity to agonists and a Type II diabetes model (ob/ob) lacking detectable alterations in the aggregation profile. Neither model showed marked increases in protein O-GlcNAcylation. Treatment of platelets with multiple O-GlcNAcase inhibitors led to O-GlcNAc accumulation on multiple platelet proteins. However, the inhibitor-induced accumulation of this modification does not correlate with any gross alterations in platelet aggregation. These data suggest that while the modification occurs in platelets, their activity is not globally sensitive to O-GlcNAc levels.
|Number of pages||5|
|Journal||Archives of Biochemistry and Biophysics|
|State||Published - Jun 1 2008|
Bibliographical noteFunding Information:
We thank the members of the Whiteheart laboratory: Dr. Elena A. Matveeva, Dr. Zubair A. Karim, Wangsun Choi, Qiansheng Ren, Chunxia Zhao, Shaojing Ye, and Rania Al Hawas for their helpful discussions and careful reading of this manuscript. This work was supported by grants from the National Institutes of Health (HL081614 and HL56652) (to S.W.W.) and from the Ohio Valley Affiliate of the American Heart Association (0415111B) (to G.L.C.).
- Protein modification
ASJC Scopus subject areas
- Molecular Biology