EFFECTS OF ALCOHOL ON IRON HOMEOSTASIS

酒精中毒和酒精性肝病(ALD)与 从缺铁性贫血到血色沉着症的铁代谢和 铁质沉着症。因为肝脏不仅是铁储存的主要部位，而且 似乎还分泌主要的铁运输蛋白--转铁蛋白 可能在酒精对肝脏的影响之间存在联系 细胞和铁的稳态，无论是作为毒性的直接结果，还是 通过某种次要的调制机制。这就是我们的目的 因此，研究酒精和铁之间的关系 (以及各种运输和储存蛋白)，以及各种肝细胞 群体，特别是肝细胞和库普弗细胞。 本项目的重点是体外检测系统，利用 从正常人肝脏中用酶法分离的特定细胞群 和治疗过的动物(老鼠)。两种大鼠血清异型转铁蛋白 铁和碘的提纯和放射性标记以及涉及的测试系统 活性肝细胞群的悬浮液将被建立和验证， 为了研究铁、转铁蛋白和各种蛋白质之间的相互作用。 肝细胞。从这些初步停牌中获得的信息将是 用作更广泛的细胞培养研究的基础。 除了在乙醇存在的情况下使用培养细胞外， 系统会因铁供应的变化、变化而受到干扰 通过添加内毒素和培养基组分。可能的 细胞：细胞间的相互作用也将通过“条件培养液”进行测试。 从一个细胞群影响铁代谢的特定方面 在其他类型的细胞中，或通过与两个或更多个细胞直接共培养 人口。 预计对人类疾病状态的推断将是 这些研究极大地促进了这一点，这将导致更好的 对人体铁代谢紊乱的认识 酒精性肝病，即铁负荷过重和贫血。

Alcoholism and alcohol liver disease (ALD) are associated with disorders of iron metabolism ranging from iron deficiency anemia to hemochromatosis and siderosis. As the liver is not only the main site of iron storage, but also secretes the major iron transport protein, transferrin, it seems likely that there is an association between the effects of alcohol on liver cells and iron homeostasis, either as a direct result of toxicity, or through some secondary mechanism of modulation. It is the aim of this study, therefore, to investigate the relationships between alcohol, iron (and various transport and storage proteins), and the various liver cell populations, in particular hepatocytes and Kupffer cells. This project focuses on examination of the system in vitro, utilizing specific populations of cells isolated enzymatically from livers of normal and treated animals (rats). The two rat serum isotransferrins will be purified and radiolabelled with iron and iodine and test systems involving suspensions of viable liver cell populations will be set up and validated, in order to study the interactions among iron, transferrin and the various liver cells. Information obtained from these initial suspensions will be used as a basis for more extensive investigations with cell cultures. In addition to the use of cultured cells in the presence of ethanol, the system will be perturbed through alterations in iron availability, changes in the media constituents and by the addition of endotoxins. The possible cell:cell interactions will also be tested by using "conditioned media" from one cell population to influence specific aspects of iron metabolism in other types of cells, or by direct co-culture with two or more cell populations. It is anticipated that extrapolation to the human disease state will be greatly facilitated by these studies and that this will lead to a better understanding of the disturbances of iron metabolism that occurs in alcoholic liver disease, i.e., iron overload and anemia.