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）是一种分泌性蛋白，是细胞外液中主要的SOD同工酶。EC-SOD的一个显著特征是其对肝素样物质的亲和力，超过99%的酶锚定在血管壁的硫酸肝素蛋白聚糖上。少量EC-SOD存在于血浆期和内皮细胞糖萼之间的循环中。我们曾报道血液透析患者血浆EC-SOD水平高于健康人。(1)尿中EC-SOD水平与尿中n -乙酰基-β- d -氨基葡萄糖酶（NAG）排泄量显著相关。EC-SOD似乎不是通过肾小球滤过从血浆中漏出，而是由肾小管或其周围组织分泌。尿EC-SOD水平也与尿camp水平显著相关。camp类似物和腺苷酸环化酶调节剂可显著刺激体外培养成纤维细胞株中EC…More -SOD的表达。此外，在体内Ellsworth-Howard试验中，尿EC-SOD升高伴随着尿cAMP升高。这些观察结果表明，刺激腺苷酸环化酶- camp系统的因子调节EC-SOD的表达。(2)超氧化物和其他氧自由基与肾功能衰竭的进展有关。EC-SOD基因的单碱基替换导致肝素结合区域的甘氨酸交换为精氨酸-213 (R213G)，导致该酶与内皮细胞的结合能力降低。血透患者EC-SOD R213G突变频率高于正常人。糖尿病（DM）患者开始血液透析3年后替代阳性患者的百分比下降。存在R213G与不存在R213G的DM患者生存率差异有统计学意义，提示EC-SOD R213G突变可作为透析患者预后的标志。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