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Involvement of transferring receptor in oxidative stress-mediated renal tubular injury

转移受体参与氧化应激介导的肾小管损伤

基本信息

批准号：
15590866
负责人：
NAKANISHI Takeshi
金额：
$ 2.3万
依托单位：
Hyogo College of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590866/
关键词：
transitional metal iron copper oxidative stress iron transporter protein cysteine 鉄輸送 Transferrin receptor ferroportin 1 尿細管間質障害

项目摘要

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.

严重蛋白尿已被证明是主要的预后因素之一。在这种情况下，大量的转铁蛋白（Tf）也在肾小球过滤，并在近端小管重吸收。同样，与Tf结合的铁也被吸收，氧化应激可能对小管产生细胞毒性作用。(1)为了阐明铁代谢与肾功能障碍之间的关系，我们研究了多形核细胞中的铁含量和铁转运蛋白。血液透析患者PMNLs中的铁含量明显高于对照组。铁含量的升高可能是由于铁输入蛋白（转铁蛋白受体）的上调和铁输出蛋白（铁转运蛋白1）的下调引起的。(2)为了阐明过渡金属是否加速了近端小管细胞的氧化应激，我们研究了硫醇和/或铜对近端小管细胞的影响。与对照组或同型半胱氨酸相比，添加半胱氨酸和铜引起严重的细胞毒性，脂质过氧化产物和羟基自由基增加。这些数据表明，半胱氨酸与同型半胱氨酸的细胞毒性不同，过渡金属加速了氧化应激。本文将进一步探讨肿瘤坏死因子α、白细胞介素-6、血管紧张素II对肾近端小管上皮细胞铁转运蛋白及氧化损伤的影响。