Crawford Garland L, Hart Gerald W, Whiteheart Sidney W
Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, 741 S. Limestone, BBSRB, Lexington, KY 40536, USA.
Arch Biochem Biophys. 2008 Jun 1;474(1):220-4. doi: 10.1016/j.abb.2008.03.014. Epub 2008 Mar 21.
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.
人们普遍认识到，糖尿病患者的血小板对低水平激动剂的反应性增强。O-连接的N-乙酰葡糖胺化与其他组织中与高血糖相关的效应有关；因此，我们研究了血小板中的这种修饰，以确定O-连接的N-乙酰葡糖胺化是否影响血小板功能。这种翻译后修饰由连接到丝氨酸和/或苏氨酸残基上的N-乙酰葡糖胺组成。我们在已知对激动剂过敏的I型糖尿病高血糖小鼠模型和聚集曲线无明显变化的II型糖尿病模型（ob/ob）的血小板中检测了O-连接的N-乙酰葡糖胺水平。两种模型均未显示蛋白质O-连接的N-乙酰葡糖胺化有明显增加。用多种O-连接的N-乙酰葡糖胺酶抑制剂处理血小板会导致多种血小板蛋白上的O-连接的N-乙酰葡糖胺积累。然而，抑制剂诱导的这种修饰积累与血小板聚集的任何总体变化均无相关性。这些数据表明，虽然这种修饰发生在血小板中，但其活性对O-连接的N-乙酰葡糖胺水平并不全局敏感。
