Ferritin and Iron Nutrition in Health and Disease

健康和疾病中的铁蛋白和铁营养

• 批准号: 6686411
• 负责人: ELIZABETH C THEIL
• 金额: $ 36.03万
• 依托单位: CHILDREN'S HOSPITAL & RES CTR AT OAKLAND
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-06-18 至 2005-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6686411
• 关键词: chemical structure function; dietary iron; disease /disorder model; female; ferritin; food; gastrointestinal nutrient absorption; hereditary hemochromatosis; human subject; iron poisoning; laboratory mouse; laboratory rabbit; laboratory rat; malnutrition; microcytic /hypochromic anemia; nutrient bioavailability; nutrition related tag; patient oriented research; phosphates; radiotracer; receptor expression; sickle cell anemia; thalassemia; tissue /cell culture

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.

目前用于管理膳食缺铁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，不遵守特定治疗以及补充剂与内源性食物成分（如植酸盐）之间的相互作用。 全世界估计有15亿人患有饮食性缺铁和贫血症。 在美国，估计育龄妇女缺铁率约为6.6%，儿童和青少年缺铁率约为11%。 认知发育缓慢和缺铁之间的联系使得潜在的经济影响很大。 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-地中海贫血）具有改变的肠道铁摄取，其特征很差。 此外，铁过载的后果是不同的SCD，β-thal和HH。 这些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，可能需要制定针对每种疾病状态的不同膳食铁来源的建议。铁蛋白是人类、其他动物和植物早期发育中铁的主要来源。 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。 在上一次授权期间，大豆铁已被证明可以轻易被人类利用，而马脾脏铁蛋白铁已被证明可以被培养细胞吸收。然而，关于从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SCD、HH和β-thal中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）矿物结构差异的营养影响尚未研究。提出了三组实验：1。Caco-2细胞中铁蛋白对铁的摄取、代谢和转运以及消化过程中铁蛋白的命运。2.在人类疾病小鼠模型中比较铁蛋白和铁盐对红细胞铁的影响。3.含高（植物）和低（动物）磷酸盐矿物的铁蛋白用于人体膳食铁的整体分析。 研究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。