Lemkadem B, Loiseau D, Larcher G, Malthiery Y, Foussard F
Laboratoire de Biochimie et de Biologie Moléculaire, CHU Angers, France.
Lipids. 1999 Dec;34(12):1281-6. doi: 10.1007/s11745-999-0479-0.
This study examines the relationship between high density lipoprotein-3 (HDL-3) glycation and cholesteryl ester transfer mediated by cholesteryl ester transfer protein (CETP). HDL-3 were glycated with various glucose concentrations (0-200 mM) for 3 d at 37 degrees C with sodium cyanoborohydride as reducing agent and antioxidants. About 47% of the lysine residues were glycated in the presence of 200 mM glucose, resulting in an increase in the cholesterol ester (CE) transfer of about 30%. Apparent kinetic parameters [expressed as maximal transfer (appT(max)) and CE concentration at half of T(max)(appK(H))] of CETP activity with glycated HDL-3 showed conflicting and paradoxical data: an increase in CETP activity associated with a decrease of CETP affinity. These alterations were not due to a change in HDL-3 lipid and protein composition nor to a peroxidative process but were associated with an increase in HDL-3 electronegativity and a decrease of HDL-3 fluidity. This study suggests that glycation modifies the apolipoprotein's conformation and solvation which are major determinants of interfacial properties of HDL-3. These modifications in turn affect CETP reactivity.
本研究考察了高密度脂蛋白3（HDL-3）糖基化与胆固醇酯转运蛋白（CETP）介导的胆固醇酯转运之间的关系。以氰基硼氢化钠作为还原剂和抗氧化剂，在37℃下，将HDL-3与不同葡萄糖浓度（0 - 200 mM）孵育3天进行糖基化。在200 mM葡萄糖存在的情况下，约47%的赖氨酸残基发生了糖基化，导致胆固醇酯（CE）转运增加了约30%。CETP与糖基化HDL-3的活性表观动力学参数[表示为最大转运量（appT(max)）和T(max)一半时的CE浓度（appK(H)）]显示出相互矛盾且反常的数据：CETP活性增加而CETP亲和力降低。这些改变并非由于HDL-3脂质和蛋白质组成的变化，也不是由于过氧化过程，而是与HDL-3负电性增加和HDL-3流动性降低有关。本研究表明，糖基化修饰了载脂蛋白的构象和溶剂化作用，而这两者是HDL-3界面性质的主要决定因素。这些修饰进而影响CETP的反应性。
