TRANSFERRIN, FERRITIN AND HEPATIC IRON METABOLISM

肝脏的铁运输量仅次于造血性骨髓 作为吸收这种必需金属的器官，它具有独特的重要性 从铁结合蛋白中，储存，用于合成铁- 依赖的酶，从衰老和受损的红细胞中回收，以及 通过胆汁排泄。此外，肝脏是铁的主要目标。 急性和慢性铁超载的毒性，并可能在 严重缺铁。实际上，铁代谢的所有方面都可能是 在这个复杂的器官中研究。 我们的方法是在细胞内寻求对铁代谢的更深层次的了解 和分子水平通过检查铁的运输，加工，储存和 对分离的肝细胞的毒性，持续关注的是 转铁蛋白红系细胞的相互作用。受体的贡献-- 介导的NAD受体非依赖性事件以及膜氧化还原过程， 将研究肝细胞从转铁蛋白中吸收铁的过程。 通过热力学、动力学和EPR光谱吞噬红细胞 Kupffer细胞，将铁蛋白作为肝细胞的铁源。 由于铁蛋白具有很大的铁吸收能力，因此可以提供铁。 以特定受体依赖的方式，对肝细胞的作用是 转铁蛋白给出的比率。我们将确定铁的摄取量是否来自 当我们研究铁蛋白的命运时，铁蛋白受细胞铁状态调节 外源性铁蛋白及其在肝细胞中的铁。为了协助这项工作， 铁蛋白受体的单抗的制备将是 承担了。最后，我们将继续研究吞噬红细胞。 Kupffer细胞，目的是确定急性铁中毒 这就是无节制地摄入红血球的致命影响。在……里面 为了验证这一假设，我们将基于自旋陷阱的研究进行关联 氧自由基，脂质过氧化的化学检测， 抗坏血酸的增杀作用及清道夫的保护作用 铁和有毒的氧物种。我们坚信，这些 研究将有助于管理铁代谢障碍- 这是人类最常见、最致残的疾病之一。

Second only to the blood-forming marrow in its traffic of iron, the liver is of unique importance as an organ where this essential metal is taken up from iron-binding proteins, stored, utilized for the synthesis of iron- dependent enzymes, recycled from senescent and damaged red blood cells, and excreted via the bile. Moreover, the liver is a major target of iron toxicity in acute and chronic iron overload, and may also sustain injury in severe iron deficiency. Virtually all aspects of iron metabolism may be studied in this complex organ. Our approach is to seek deeper understanding of iron metabolism at cellular and molecular levels by examining iron transport, processing, storage and toxicity in isolated liver cells, Of continuing interest is the interaction of transferrin erythroid cells. The contributions of receptor- mediated nad receptor-independent events, and of membrane redox processes, in the uptake of iron from transferrin by hepatocytes will be investigated by thermodynamic, kinetic and EPR spectroscopic erythrophagocytosing Kupffer cells, deals with ferritin as an iron source for hepatocytes. Because of its large iron-accommodating capacity, ferritin may provide iron to hepatocytes, in specific receptor-dependent fashion, at 50 times the rate given by transferrin. We will determine whether iron uptake from ferritin is regulated by cellular iron status, as we examine the fate of exogenous ferritin and its iron in the hepatocyte. To assist in this work, preparation of monoclonal antibodies to the ferritin receptor will be undertaken. Finally, we will pursue studies of erythrophagocytosing Kupffer cells, with a goal of determining whether acute iron toxicity underlies the lethal effects of unrestrained red cell ingestion. In testing this hypothesis, we will correlate studies based on spin trapping of oxygen-derived radicals, chemical detection of lipid peroxidation, potentiation of killing by ascorbate and protective effects of scavengers of iron and noxious oxygen species. Our conviction is that these investigations will contribute in managing disorders of iron metabolism - among the most common and most disabling of humankind's ills.