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

内皮细胞结合超氧化物歧化酶(EC-SOD)在肾脏疾病发生发展筛查中的应用

基本信息

批准号：
10672044
负责人：
ADACHI Tetsuo
金额：
$ 2.11万
依托单位：
Gifu Pharmaceutical university
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

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

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的一个突出特征是其对肝素样物质的亲和力，并且超过99%的这种酶锚定在血管壁中的硫酸乙酰肝素蛋白聚糖上。EC-SOD的小部分存在于血浆相和内皮的糖萼之间平衡的循环中。我们曾报道血液透析患者血浆EC-SOD水平高于健康人。(1)尿EC-SOD水平与尿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漏出，而是从肾小管或其周围组织中分泌。尿EC-SOD水平与尿cAMP水平也呈显著相关。cAMP类似物和腺苷酸环化酶调节剂显著刺激EC的表达 ...更多信息 - 体外培养的成纤维细胞系中的SOD。在体内Ellssen-Howard试验中，尿EC-SOD升高，同时伴有尿cAMP升高。总之，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衰竭的进展有关。EC-SOD基因的一个单碱基取代导致肝素结合结构域中甘氨酸被精氨酸-213（R213 G）取代，导致该酶与内皮细胞的结合能力降低。血液透析患者EC-SOD基因R213 G突变频率高于健康人。糖尿病（DM）患者血液透析开始后3年，置换阳性患者的百分比呈下降趋势。有无R213 G的DM患者生存率差异有统计学意义。提示EC-SOD基因R213 G突变可能是透析患者预后的一个指标。少