NONENZYMATIC GLYCATION OF HUMAN EXTRACELLULAR SUPEROXIDE-DISMUTASE
NONENZYMATIC GLYCATION OF HUMAN EXTRACELLULAR SUPEROXIDE-DISMUTASE
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DOI：
10.1042/bj2790263
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发表时间：
1991-10-01
影响因子：
4.1
通讯作者：
MARKLUND, SL
中科院分区：
文献类型：
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作者：
ADACHI, T;OHTA, H;MARKLUND, SL
分泌酶胞外超氧化物歧化酶（EC-SOD）在血浆中就肝素亲和力而言是异质的，并且可分为三个组分，缺乏亲和力的A，具有中等亲和力的B和具有高亲和力的C。C组分在血浆相和内皮表面上的硫酸乙酰肝素蛋白聚糖之间形成平衡。体外EC SOD C可随时间发生糖基化。酶的活性不受影响，在糖化EC-SOD，但高肝素亲和性失去了约一半的研究糖化馏分。肝素的加入降低了体外糖基化，赖氨酸特异性试剂三硝基苯磺酸修饰的EC-SOD C在体外不能发生糖基化。研究结果表明，糖化位点是本地化的，而远离活性位点，并可能发生在赖氨酸残基的肝素结合结构域中的C-末端的酶。糖尿病患者血清中糖基化EC-SOD的比例明显高于正常人。在各亚组分中，EC SOD B的糖化程度最高，其次是EC SOD A。EC-SOD-C的糖基化程度较低。研究结果表明，糖基化是导致血浆EC-SOD肝素亲和力不均一的因素之一。由于这种现象在糖尿病中增加，因此在这种疾病中细胞表面相关的EC-SOD可能减少，增加了细胞对细胞外空间中产生的超氧自由基的易感性。
The secretory enzyme extracellular superoxide dismutase (EC-SOD) is in plasma heterogeneous with regard to heparin-affinity and can be divided into three fractions, A that lacks affinity, B with intermediate affinity and C with high affinity. The C fraction forms an equilibrium between the plasma phase and heparan sulphate proteoglycan on the surface of the endothelium. In vitro EC-SOD C could be time-dependently glycated. The enzyme activity was not affected in glycated EC-SOD, but the high heparin-affinity was lost in about half of the studied glycated fraction. Addition of heparin decreased the glycation in vitro, and EC-SOD C modified with the lysine-specific reagent trinitrobenzenesulphonic acid could not be glycated in vitro. The findings suggest that the glycation sites are localized rather far away from the active site and may occur on lysine residues in the heparin-binding domain in the C-terminal end of the enzyme. The proportion of glycated EC-SOD in serum of diabetic patients was considerably higher than in normal subjects. Of the subfractions, EC-SOD B was by far the most highly glycated, followed by EC-SOD A. EC-SOD C was glycated only to be a minor extent. The findings suggest that glycation is one of the factors that contribute to the heterogeneity in heparin-affinity of plasma EC-SOD. Since this phenomenon is increased in diabetes, the cell-surface-associated EC-SOD may be decreased in this disease, increasing the susceptibility of cells to superoxide radicals produced in the extracellular space.