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膜流动性与蛋白质糖基化程度有关,但与糖尿病患者和对照受试者分离的血小板膜中胆固醇与磷脂摩尔比的改变无关。

Membrane fluidity is related to the extent of glycation of proteins, but not to alterations in the cholesterol to phospholipid molar ratio in isolated platelet membranes from diabetic and control subjects.

作者信息

Winocour P D, Watala C, Kinglough-Rathbone R L

机构信息

Department of Pathology, McMaster University, Hamilton, Ontario, Canada.

出版信息

Thromb Haemost. 1992 May 4;67(5):567-71.

PMID:1519216
Abstract

Platelets from diabetic subjects are hypersensitive to aggregating agents in vitro. Membrane fluidity modulates cell function and we previously reported reduced membrane fluidity associated with hypersensitivity to thrombin in intact platelets from diabetic subjects. Reduced membrane fluidity and hypersensitivity to agonists has also been reported in platelets from non-diabetic subjects whose platelets have an increased cholesterol/phospholipid molar ratio. Glycation of platelet membrane proteins is enhanced in diabetic subjects, and could contribute to the decreased membrane fluidity in these platelets. We examined the relation among fluidity, cholesterol/phospholipid molar ratio, and glycation of proteins in isolated platelet membranes from diabetic and control subjects. Seven poorly controlled diabetic subjects were compared with 7 age- and sex-matched control subjects. The mean steady-state fluorescence polarization value in 1,6-diphenyl-1,3,5-hexatriene-labeled isolated platelet membranes from diabetic subjects (0.184 +/- 0.004) was significantly greater than from control subjects (0.171 +/- 0.004, p less than 0.01); thus, fluidity in platelet membranes from diabetic subjects is decreased. Reduced fluidity in platelet membranes from diabetic subjects could not be attributed to changes in the cholesterol/phospholipid molar ratio. Total or very low density (VLDL), low density (LDL), or high density (HDL3) lipoprotein cholesterol concentration in plasma was not significantly different between groups, but the ratio of VLDL+LDL to HDL2 + HDL3 cholesterol was significantly greater in diabetic subjects (4.79 +/- 0.73) than in control subjects (2.54 +/- 0.30, p less than 0.02). Proteins were glycated significantly more extensively in platelet membranes from diabetic subjects (25.5 +/- 0.9 nmol glucose/mg protein) than those from control subjects (21.0 +/- 0.6 nmol glucose/mg protein, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

糖尿病患者的血小板在体外对聚集剂高度敏感。膜流动性调节细胞功能,我们之前报道过,糖尿病患者完整血小板中膜流动性降低与对凝血酶的超敏反应有关。在非糖尿病患者的血小板中,当胆固醇/磷脂摩尔比增加时,也有膜流动性降低和对激动剂超敏反应的报道。糖尿病患者血小板膜蛋白的糖基化增强,这可能导致这些血小板膜流动性降低。我们研究了糖尿病患者和对照者分离的血小板膜中流动性、胆固醇/磷脂摩尔比和蛋白糖基化之间的关系。将7名血糖控制不佳的糖尿病患者与7名年龄和性别匹配的对照者进行比较。糖尿病患者用1,6-二苯基-1,3,5-己三烯标记的分离血小板膜的平均稳态荧光偏振值(0.184±0.004)显著高于对照者(0.171±0.004,p<0.01);因此,糖尿病患者血小板膜的流动性降低。糖尿病患者血小板膜流动性降低不能归因于胆固醇/磷脂摩尔比的变化。两组血浆中总胆固醇或极低密度(VLDL)、低密度(LDL)或高密度(HDL3)脂蛋白胆固醇浓度无显著差异,但糖尿病患者中VLDL+LDL与HDL2+HDL3胆固醇的比值(4.79±0.73)显著高于对照者(2.54±0.30,p<0.02)。糖尿病患者血小板膜中蛋白的糖基化程度(25.5±0.9 nmol葡萄糖/mg蛋白)明显高于对照者(21.0±0.6 nmol葡萄糖/mg蛋白,p<0.001)。(摘要截选至250字)

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