| Project/Area Number |
10672044
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Gifu Pharmaceutical university |
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Principal Investigator |
ADACHI Tetsuo Gifu Pharm. Univ. / Lab. of Clin. Pharm. / associate professor, 薬学部, 助教授 (40137063)
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| Co-Investigator(Kenkyū-buntansha) |
YAMADA Harutaka Aichi Med. Univ. / 1st Dept. of Internal Med. / associate professor, 医学部, 講師 (70230472)
HARA Hirokazu Gifu Pharm. Univ. / Lab. of Clin. Pharm. / research assistant, 薬学部, 研究助手 (30305495)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | Extracellular-superoxide dismutase / cAMP / Hemodialysis patients / Diabetes mellitus / Heparin / Active oxygens / 加齢 / ホモシステイン / スーパーオキシドジスムターゼ / 糸球体 / 糖尿病性腎症 / 一酸化窒素 |
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| Research Abstract |
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
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