EFFECTS OF ALCOHOL ON IRON HOMEOSTASIS

酒精中毒和酒精性肝病（ALD）与以下疾病有关： 从缺铁性贫血到血色病的铁代谢， 铁质沉着症 由于肝脏不仅是铁储存的主要场所， 似乎也分泌主要的铁转运蛋白，转铁蛋白， 酒精对肝脏的影响 细胞和铁稳态，无论是作为毒性的直接结果，或 通过某种次要的调节机制 这是我们的目的 研究，因此，调查酒精，铁， (and各种运输和储存蛋白），以及各种肝细胞 细胞群，特别是肝细胞和枯否细胞。 本项目的重点是在体外检查系统，利用 从正常人的肝脏中酶促分离的特定细胞群 和处理的动物（大鼠）。 两种大鼠血清异转铁蛋白将 纯化并用铁和碘进行放射性标记， 将建立并验证活肝细胞群的悬浮液， 为了研究铁，转铁蛋白和各种 肝细胞 从这些初步暂停获得的信息将 用作更广泛的细胞培养研究的基础。 除了在乙醇存在下使用培养的细胞之外， 系统将受到干扰，通过改变铁的可用性，变化 培养基成分和内毒素的添加。 可能的 还将使用“条件培养基”测试细胞：细胞相互作用 从一个细胞群体中影响铁代谢的特定方面 在其它类型细胞中，或通过与两种或多种细胞直接共培养 人口。 预计将外推至人类疾病状态 这将大大促进这些研究，这将导致更好的 了解铁代谢紊乱发生在 酒精性肝病，即，铁超载和贫血。

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.