Application of endothelial cell-binding superoxide dismutase (EC-SOD) on screening of the initiation-progress of renal diseases

细胞外超氧化物歧化酶(EC-SOD)是一种分泌型蛋白质，是细胞外液中主要的超氧化物歧化酶同工酶。EC-SOD的一个显著特征是它对类肝素物质的亲和力，并且99%以上的这种酶被锚定在血管壁中的硫酸肝素蛋白多糖上。EC-SOD的一小部分存在于循环中，平衡于血浆相和内皮细胞的糖萼之间。我们曾报道血液透析患者血浆EC超氧化物歧化酶水平高于正常人。(1)尿液EC超氧化物歧化酶水平与尿N-乙酰-β-D-氨基葡萄糖苷酶(NAG)排泄量呈显著正相关。EC-SOD似乎不是通过肾小球滤过从血浆中泄漏出来的，而是从肾小管或其周围组织中分泌出来的。尿EC-SOD水平与尿cAMP水平呈显著正相关。CAMP类似物和腺苷环化酶调节剂显著刺激EC…的表达体外培养成纤维细胞系中More-SOD的表达。此外，体内Ellsworth-Howard试验显示，随着尿cAMP水平的升高，尿EC-SOD也随之升高。综上所述，这些观察结果提示，刺激腺苷环化酶-cAMP系统的因子(S)调节EC-超氧化物歧化酶的表达。(2)超氧阴离子和其他氧自由基参与了肾功能衰竭的进展。EC-SOD基因的单碱基替换导致肝素结合区的精氨酸-213(R213G)与甘氨酸的交换，导致该酶与内皮细胞的结合能力降低。维持性血液透析患者EC-SOD基因R213G突变频率明显高于正常人。糖尿病(DM)患者血液透析开始3年后，替换阳性患者的比例呈下降趋势。糖尿病患者中有无R213G的患者存活率差异有统计学意义。提示EC-SOD基因R213G突变可作为判断血液透析患者预后的指标。较少

Extracellular-superoxide dismutase (EC-SOD) is a secretory protein that is the major SOD isozyme in extracellular fluids. A prominent feature of EC-SOD is its affinity to heparin-like substances and more than 99% of this enzyme is anchored to heparan sulfate proteoglycans in the blood vessel walls. The minor parts of EC-SOD is present in the circulation in equilibrium between the plasma phase and the glycocalyx of the endothelium. We have reported that the plasma levels of EC-SOD was higher in hemodialysis patients than in healthy persons.(1) The urinary EC-SOD level was significantly correlated with the urinary excretion of N-acetyl-β-D-glucosaminidase (NAG). EC-SOD appears not to be leaked from the plasma by glomerular filtration, but rather to be secreted from the renal tubule or its surrounding tissues. The urinary EC-SOD level was also significantly correlated with the urinary camp level. camp analogues and adenylate cyclase modulators significantly stimulated the expression of EC … More -SOD in cultured fibroblast cell lines in vitro. Moreover, in vivo Ellsworth-Howard tests, increased urinary EC-SOD accompanied with the elevations of urinary cAMP. Together these observations suggest that factor(s) that stimulate the adenylate cyclase-cAMP system regulate the EC-SOD expression.(2) The superoxide and other oxygen radicals have been implicated in the progress of renal failure. A single base substitution of EC-SOD gene causing exchange of glycine for arginine-213 (R213G) in the heparin-binding domain leads the reduction of the binding capability of this enzyme to endothelial cells. The frequency of the R213G mutation of EC-SOD were higher in hemodialysis patients than in healthy persons. Percentage of substitution positive patients was declining 3 years after the start of hemodialysis in patients with diabetes mellitus (DM). There were significant differences in the survival rate between patients with and without R213G in DM. These results suggest that the R213G mutation of EC-SOD could be a prognostic marker of dialysis patients. Less