Murine platelets are not regulated by O-linked beta-N-acetylglucosamine.
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.
Crawford
Garland L
GL
Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, 741 S. Limestone, BBSRB, Lexington, KY 40536, USA.
Hart
Gerald W
GW
Whiteheart
Sidney W
SW
D000117:Acetylglucosamine / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001792:Blood Platelets / Q000378:metabolism*; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL; D010974:Platelet Aggregation
D001786:Blood Glucose; D000117:Acetylglucosamine