Sturm Brigitte, Goldenberg Hans, Scheiber-Mojdehkar Barbara
Department of Medical Chemistry, University of Vienna, Austria.
Eur J Biochem. 2003 Sep;270(18):3731-8. doi: 10.1046/j.1432-1033.2003.03759.x.
Intravenous iron, used for the treatment of anemia in chronic renal failure and other diseases, represents a possible source of free iron in tissue cells, particularly in the liver. In this study we examined the effect of different sources of intravenous iron (IVI) on the labile iron pool (LIP) which represents the nonferritin-bound, redox-active iron that is implicated in oxidative stress and cell injury. Furthermore, we examined the role of the LIP for the synthesis of ferritin. We used HepG2 cells as a well known model for hepatoma cells and monitored the LIP with the metal-sensitive fluorescent probe, calcein-AM, the fluorescence of which is quenched on binding to iron. We showed that steady state LIP levels in HepG2 cells were increased transiently, up to three-fold compared to control cells, as an adaptive response to long-term IVI exposure. In relation to the amount of iron in the LIP, the ferritin levels increased and the iron content of ferritin decreased. As any fluctuation in the LIP, even when it is only transient (e.g. after exposure to intravenous iron in this study), may result either in impairment of synthesis of iron containing proteins or in cell injury by pro-oxidants. Such findings in nonreticuloendothelial cells may have important implications in the generation of the adverse effects of chronic iron exposure reported in dialysis patients.
静脉注射铁剂用于治疗慢性肾衰竭及其他疾病中的贫血，它可能是组织细胞中游离铁的一个来源，尤其是在肝脏中。在本研究中，我们检测了不同来源的静脉注射铁（IVI）对不稳定铁池（LIP）的影响，LIP代表非铁蛋白结合的、具有氧化还原活性的铁，与氧化应激和细胞损伤有关。此外，我们还检测了LIP在铁蛋白合成中的作用。我们使用HepG2细胞作为肝癌细胞的一个知名模型，并使用金属敏感荧光探针钙黄绿素-AM监测LIP，其荧光在与铁结合时会淬灭。我们发现，作为对长期IVI暴露的适应性反应，HepG2细胞中的稳态LIP水平会短暂升高，与对照细胞相比最多可升高三倍。相对于LIP中的铁含量，铁蛋白水平升高，而铁蛋白中的铁含量降低。由于LIP的任何波动，即使只是短暂的波动（如本研究中静脉注射铁剂后的波动），都可能导致含铁蛋白质合成受损或被促氧化剂损伤细胞。非网状内皮细胞中的这些发现可能对透析患者中慢性铁暴露的不良反应产生具有重要意义。
