TRANSFERRIN, FERRITIN AND HEPATIC IRON METABOLISM

在运输铁方面仅次于造血骨髓的是肝脏 作为吸收这种基本金属的器官， 从铁结合蛋白质，储存，用于铁的合成， 依赖酶，从衰老和受损的红细胞中回收， 通过胆汁排出。 此外，肝脏是铁的主要靶点 急性和慢性铁过载的毒性，也可能在 严重缺铁 铁代谢的几乎所有方面都可能 在这个复杂的机构中进行研究。 我们的方法是寻求更深入地了解铁代谢在细胞 和分子水平，通过检查铁的运输，加工，储存和 在离体肝细胞中的毒性，持续的兴趣是 转铁蛋白红系细胞的相互作用。 受体的作用- 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摄取铁的作用 通过热力学、动力学和EPR光谱的噬红细胞作用 枯否细胞，处理铁蛋白作为肝细胞的铁源。 由于其大的铁容纳能力，铁蛋白可提供铁 以特异性受体依赖的方式，以50倍于 由转铁蛋白给出的速率。 我们将确定铁的吸收是否来自 铁蛋白受细胞铁状态的调节，因为我们研究了铁蛋白的命运， 外源性铁蛋白及其铁在肝细胞中的作用。 为了协助这项工作， 铁蛋白受体的单克隆抗体的制备将是 进行。 最后，我们将继续研究红细胞吞噬 枯否细胞，目的是确定急性铁中毒是否 是不受限制的红细胞摄入致命影响的基础。 在 为了验证这一假设，我们将对基于自旋捕获的研究进行关联， 氧衍生自由基，脂质过氧化的化学检测， 抗坏血酸的增强杀伤作用和清道夫的保护作用 铁和有毒氧的混合物 我们的信念是， 调查将有助于管理铁代谢紊乱- 是人类最常见也是最致命的疾病之一

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.