2004 Fiscal Year Final Research Report Summary
Involvement of transferring receptor in oxidative stress-mediated renal tubular injury
| Project/Area Number |
15590866
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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 |
Kidney internal medicine
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| Research Institution | Hyogo College of Medicine |
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Principal Investigator |
NAKANISHI Takeshi Hyogo college of Medichie, Faculty of Medicine, Professor, 医学部, 教授 (70217769)
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| Co-Investigator(Kenkyū-buntansha) |
OTAKI Yoshinaga Hyogo college of Medicine, Faculty of Medicine, Research Associate, 医学部, 助手 (40388814)
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| Project Period (FY) |
2003 – 2004
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| Keywords | transitional metal / iron / copper / oxidative stress / iron transporter protein / cysteine |
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| Research Abstract |
Severe proteinuria has been already demonstrated to be one of the major prognostic factors. In this situation, substantial amount of transferrin(Tf) also filtered at glomeruli, and reabsorbed at the proximal tubules. Similarly, ferric iron bound to Tf is also absorbed, which might cause cytotoxic effect to tubules by oxidative stress. (1)For the purpose of clarifying the relation between iron metabolism and renal dysfunction, iron contents and iron transport proteins in polymorphonuclear cells were investigated. Iron content in PMNLs in hemodialysis patients was significantly higher in control. The rise in iron content might be caused by the upregulation of iron-import protein (transferrin receptor) and downregulation of iron-export protein (ferroportin 1). (2)For the purpose of clarifying whether transitional metal accelerate the oxidative stress in proximal tubular cells, the effect of thiols and/or copper on proximal tubular cells were investigated. The addition of both cysteine and copper cause severe cell toxicity, the increase in lipid peroxidation product and hydroxyl radical, compared to control, or homocysteine. These data suggested that the cell toxicity of cysteine was different from that of homocysteine, and transitional metal accelerated the oxidative stress. Hereafter, the effects of tumor necrosis factor α、interleukin-6、Angiotensin II on iron transport proteins and oxidative damage in Renal Proximal Tubular Epithelial Cells will be investigated.
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