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.

严重的蛋白尿已经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）也在肾小球上过滤，并在代理管处重新吸收。同样，与TF结合的铁铁也被吸收，这可能会通过氧化应激对试管引起细胞毒性作用。（1）为了阐明铁代谢与肾功能障碍，在多形核细胞中铁含量和铁转运蛋白之间的关系。血液透析患者的PMNL中的铁含量在对照中明显更高。铁含量的升高可能是由于铁IMPORT蛋白（转铁蛋白受体）的上调和铁export蛋白的下调（铁蛋白1）引起的。（2）为了阐明过渡金属是否加速了近端管状细胞中的氧化应激，硫醇和/或铜对它们研究的近端管状细胞的影响。与对照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的增加。这些数据表明，半胱氨酸的细胞毒性与同型半胱氨酸的毒性不同，并且过渡金属加速了氧化应激。此后，将研究肿瘤坏死因子α，白细胞介素-6，血管紧张素II对铁转运蛋白的影响以及肾近端肾小管上皮细胞中氧化损伤的影响。