Ferritin and Iron Nutrition in Health and Disease

现有的膳食铁缺乏管理策略的替代方案可以帮助弥补食物补充的相对费用，弥补特定疗法的不依从性以及补充剂与内源性食物成分（如植酸盐）之间的相互作用。据估计，全世界有15亿人缺铁和贫血。在美国，估计育龄妇女缺铁的比例约为6.6%，儿童和青少年缺铁的比例约为11%。认知发展缓慢和缺铁之间的联系，使潜在的经济影响巨大。某些疾病状态，如镰状细胞病（SCD）、遗传性血色素沉着症（HH）和β -地中海贫血（β -thal）改变了肠道铁摄取，但这一特征尚不明确。此外，铁超载对SCD、β -thal和HH的影响是不同的。这样的观察结果说明了处理铁的疾病依赖性变化。有了更多的信息，可能需要针对每种疾病状态制定不同的膳食铁来源建议。铁蛋白是人类和其他动植物早期发育的主要铁来源。人类食用的豆类种子富含铁和铁蛋白。大豆种子铁（主要是铁蛋白）和马脾铁蛋白是缺铁大鼠可用的铁来源。在最后的拨款期间，大豆铁已被证明易于人类获得，马脾铁蛋白铁已被培养的细胞所吸收。然而，关于铁蛋白摄取铁的分子机制的研究还很少。铁蛋白铁对正常或疾病SCD、HH和β -thal状态下铁摄取和输出蛋白表达的影响尚不清楚，植物（高磷酸盐）和动物（低磷酸盐）矿物质结构差异的营养影响尚未探索。提出了三组实验：1。Caco-2细胞中铁蛋白对铁的摄取、代谢和运输以及铁蛋白在消化过程中的命运。2. 人疾病小鼠模型中铁蛋白与铁盐对红细胞铁的影响比较。3. 铁蛋白与高（植物）和低（动物）磷酸盐矿物对人体膳食铁的分析。结果将阐明铁蛋白铁摄取的机制，并表征铁摄取的分子遗传差异，以改善健康和疾病的膳食铁来源。

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.