Ferritin and Iron Nutrition in Health and Disease

目前管理膳食铁缺乏的管理策略的替代方案可以帮助补偿食物补充剂的相对费用、不遵守特定疗法的费用以及补充剂与植酸盐等内源性食物成分之间的相互作用。据估计，全世界有15亿人饱受膳食缺铁和贫血的困扰。在美国，估计育龄妇女缺铁约为6.6%，儿童和青少年缺铁约为11%。认知发育缓慢和缺铁之间的联系使潜在的经济影响很大。某些疾病状态，如镰刀细胞病(SCD)、遗传性血色沉着症(HH)和β地中海贫血(β地中海贫血)改变了肠道铁摄取，但这种改变的特征很差。此外，铁超载对SCD、β-Thal和HH的后果是不同的。这些观察结果说明了在处理铁的过程中会出现疾病相关的变化。有了更多的信息，可能需要针对每个疾病州的不同饮食铁源制定建议。铁蛋白是人类、其他动植物早期发育过程中铁的主要来源。人类食用的豆类种子富含铁和铁蛋白。大豆籽铁(主要是铁蛋白)和马脾铁蛋白是缺铁大鼠的有效铁源。在上一次赠款期间，已经证明大豆铁对人类很容易获得，而马的脾铁蛋白铁被培养的细胞摄取。然而，关于铁蛋白摄取铁的分子机制的信息很少。铁蛋白铁对正常或疾病状态下SCD、HH和β-Thal铁摄取和输出蛋白表达的影响尚不清楚，植物(高磷)和动物(低磷)矿物结构差异对营养的影响也未被探索。提出了三组实验：1.Caco-2细胞对铁蛋白铁的摄取、代谢和转运，以及铁蛋白在消化过程中的去向。2.在小鼠人类疾病模型中比较铁蛋白和铁盐对红细胞铁的影响。3.人体膳食铁中含有高(植物)和低(动物)磷矿物质的铁蛋白-全身分析。这些结果将阐明铁蛋白铁吸收的机制，并表征铁吸收的分子遗传差异，以改善健康和疾病中的膳食铁源。

Alternatives to current management strategies for managing dietary iron deficiency can help compensate for the relative expense of food supplementation, for noncompliance with specific therapies and for interactions between supplements and endogenous food components such as phytate. Dietary iron deficiency and anemia afflict an estimated 1.5 billion people world. In the United States estimates of iron deficiency in women of reproductive age are approximately 6.6 percent and for children and adolescents, approximately 11 percent. The link between slow cognitive development and iron deficiency makes the potential economic impact great. Certain disease states such as Sickle Cell Disease (SCD), hereditary hemochromatosis (HH), and beta-thalassemia (beta-thal) have altered gut iron uptake that is poorly characterized. In addition, the consequences of Fe overload are different for SCD, beta-thal and HH. Such observations illustrate disease-dependent variations in handling iron. With more information, recommendations for different dietary iron sources in each disease states might need to be developed. Ferritin is a major source of iron in the early development of humans, other animals and plants. Legume seeds consumed by humans are rich in iron and ferritin. Soybean seed iron (largely ferritin) and horse spleen ferritin are available iron sources for iron deficient rats. During the last grant period soybean iron has been shown to be readily available to humans and horse spleen ferritin iron was shown to be taken up by cultured cells. However, there is little information about the molecular mechanism of iron uptake from ferritin. The impact of ferritin iron on expression of iron uptake and export proteins in normal or the disease states SCD, HH and beta-thal is not known, and the nutritional impact of differences in the mineral structure of plants (high phosphate) and animals (low phosphate) has not been explored. Proposed are three sets of experiments: 1. Uptake, metabolism and transport of iron from ferritin in Caco-2 cells and the fate of ferritin during digestion. 2. Comparison of ferritin and iron salts for of red cell iron, in mouse models of human disease. 3. Ferritin with high (plant) and low (animal) phosphate mineral for dietary iron in humans-whole body analyses. The results will clarify mechanisms of ferritin iron uptake and characterize molecular genetic differences in iron uptake for improving dietary iron sources in health and disease.