Enns Caroline A
Department of Cell and Developmental Biology, Oregon Health & Science University, Portland, OR 97239, USA.
Biol Res. 2006;39(1):105-11. doi: 10.4067/s0716-97602006000100013.
Hereditary hemochromatosis (HH) is the most common inherited disorder in people of Northern European descent. Over 83% of the cases of HH result from a single mutation of a Cys to Tyr in the HH protein. HFE. This mutation causes a recessive disease resulting in an accumulation of iron in selected tissues. Iron overload damages these organs leading to cirrhosis of the liver, diabetes, cardiomyopathy, and arthritis. The mechanism by which HFE influences iron homeostasis in cells and in the body remains elusive. Lack of functional HFE in humans produces the opposite effects in different cell types in the body. In the early stages of the disease. Kupffer cells in the liver and enterocytes in the intestine cells are iron depleted and have low intracellular ferritin levels, whereas hepatocytes in the liver are iron overloaded and have high intracellular iron levels. This review gives the background and a model as to possible mechanisms of how HFE could exert different effects on iron homeostasis in different cell types.
遗传性血色素沉着症（HH）是北欧血统人群中最常见的遗传性疾病。超过83%的HH病例是由HH蛋白HFE中一个半胱氨酸（Cys）突变为酪氨酸（Tyr）所致。这种突变导致一种隐性疾病，致使铁在特定组织中蓄积。铁过载会损害这些器官，进而引发肝硬化、糖尿病、心肌病和关节炎。HFE影响细胞和体内铁稳态的机制仍不清楚。人类缺乏功能性HFE会在体内不同细胞类型中产生相反的效应。在疾病早期，肝脏中的库普弗细胞和肠道细胞中的肠上皮细胞铁缺乏且细胞内铁蛋白水平较低，而肝脏中的肝细胞铁过载且细胞内铁水平较高。本综述给出了关于HFE如何对不同细胞类型中的铁稳态产生不同影响的可能机制的背景及模型。
