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

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结合的三价铁也被吸收，这可能通过氧化应激对肾小管产生细胞毒性作用。（1）为了阐明铁代谢与肾功能损害的关系，本研究对多形核细胞铁含量和铁转运蛋白进行了研究。血液透析患者PMNLs中铁含量显著高于对照组。铁含量的增加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。（2）为了阐明过渡金属是否加速近端肾小管细胞的氧化应激，研究了硫醇和/或铜对近端肾小管细胞的影响。与对照组或同型半胱氨酸相比，半胱氨酸和铜的添加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不同，过渡金属加速氧化应激。本研究将探讨肿瘤坏死因子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。

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.