EFFECTS OF ALCOHOL ON IRON HOMEOSTASIS

酒精中毒和酒精性肝病通常与 铁稳态紊乱，从缺铁性贫血到 血色沉着症和铁质沉着症。由于肝脏不仅是一个主要的网站， 铁储存，而且还合成转铁蛋白，主要血浆铁 转运蛋白，任何肝功能障碍，如酒精引起的肝功能障碍 可能会导致这个器官铁代谢的剧烈变化。是 因此，本项目的主要目的是评估 酒精对大鼠肝脏铁稳态的影响，以及其他因素， 作为循环内毒素（在酒精性肝病中增加）。 由于脂肪酸与铁转运和脂肪酸 代谢被酒精干扰，这也是检查的次要目的。 它们在与酒精相关的铁代谢改变中的作用 实现这些目标，将达到以下目标：（1） 将在肝细胞和枯否细胞中检查铁负荷或消耗 从体内和体外的酒精率。铁摄取转铁蛋白 合成、细胞铁动员和转铁蛋白受体 浓度和回收率将被定量。(2)蜂窝 这些动物中转铁蛋白受体的控制将是 研究了 信使和蛋白质合成的速率将是 测量，将退化。 该系统将与 去唾液酸糖蛋白和转铁蛋白的合成和分泌， 铁蛋白(3)内毒素对酒精中毒大鼠铁代谢的影响 将使用上述系统进一步分析大鼠。长期 在这些速率中诱导内毒素抗体滴度的影响 也将被审查。(4)脂肪酸摄取与铁的关系 将在急性和慢性酒精大鼠中评估代谢。两条肠子 将使用十二指肠袢、分离的细胞和 膜囊泡 预计将外推至人类疾病状态 这些研究将大大促进，并将导致更好的 了解铁代谢紊乱发生在 酗酒和酒精性肝病。

Alcoholism and alcoholic liver disease are often associated with disturbances to iron homeostasis, ranging from iron deficiency anemia to hemochromatosis and siderosis. Since the liver is not only a major site of iron storage, but also synthesizes transferrin, the major plasma iron transport protein, any hepatic dysfunction, such as that caused by alcohol may result in dramatic alterations to iron metabolism in this organ. It is therefore the primary aim of this project to assess the influence of alcohol on liver iron homeostasis in the rat, as well as other factors such as circulating endotoxins (which are increased in alcoholic liver disease). Since fatty acids have been implicated in iron transport and fatty acid metabolism is disturbed by alcohol, it is also a secondary aim to examine their role in the altered iron metabolism associated with alcohol To achieve these aims, the following goals will be met: (1) The effects of iron loading or depletion will be examined in hepatocytes and Kupffer cells from alcoholic rate in vivo and in vitro. Transferrin iron uptake, ferritin synthesis, cellular iron mobilization and transferrin receptor concentration and rate of recycling will be quantitated. (2) The cellular control of transferrin receptors in these animals will be investigated. The rate of messenger and protein synthesis will be measured, as will degradation. This system will be compared to that for asialoglycoproteins and the synthesis and secretion of transferrin and ferritin. (3) The effects of endotoxins on iron metabolism in alcoholic rats will be analyzed further, using the systems above. The long-term effects of the induction of antibody titers to endotoxins in these rate will also be examined. (4) The relationship of fatty acid uptake to iron metabolism will be assessed in acute and chronic alcoholic rats. Both gut and liver uptake will be analyzed, using duodenal loops, isolated cells and membrane vesicles. It is anticipated that extrapolation to the human disease state will be greatly facilitated by these studies and will lead to a better understanding of the disturbances of iron metabolism that occur in alcoholics and alcoholic liver disease.