Iron uptake, utilization and storage in mice

小鼠对铁的摄取、利用和储存 全铁缺乏与生命格格不入，而铁过量则是危险的有毒物质。因此，哺乳动物体内的铁水平被严格维持在平衡状态。铁的新陈代谢受到调控，从而提供足够的铁来满足身体的需要(几乎每个细胞，特别是红细胞)，但同时通过安全地储存在特殊分子中来避免其毒性，因为游离铁可以参与自由基的形成。 由于肠道对铁的吸收不足以满足日常的红系需求，铁的循环和再利用是铁稳态的重要方面。负责有效回收铁的细胞属于单核吞噬细胞，其中包括巨噬细胞。组织周转至关重要的一个部分是造血系统。在成年小鼠中，每天大约产生2200万个淋巴细胞，为了保持它们的数量不变，每天必须有相同数量的细胞死亡。然而，目前缺乏必要的实用和灵敏的工具来研究组织铁含量的时间和空间变化。 总体而言，我们的目标是了解细胞和有机体如何调节它们的铁含量，以及不同的组织如何协调铁的分布，以响应铁稳态的改变。 我们建议解开动态平衡的几个基本方面：细胞铁摄取和循环的调节，肠道铁吸收和脑铁代谢。 我们期待这项基础性研究将为铁生物学和动物生理学领域做出重大贡献。由于铁代谢与哺乳动物有显著的相似之处，而且铁对生物系统是必不可少的，因此通过研究小鼠的铁代谢所获得的知识很可能与更多的应用领域有关，如人类健康和畜牧业。

Iron uptake, utilization and storage in mice Total iron deficiency is incompatible with life, whereas iron excess is dangerously toxic. Thus, body iron levels in mammals are tightly maintained in balance. Iron metabolism is regulated such that sufficient iron is provided for body needs (to virtually every cell and, in particular, red blood cells), but at the same time avoiding its toxicity through safe storage in specialized molecules, because free iron can participate in the formation of free radicals. Because iron absorption from the intestine is insufficient to meet daily erythroid demands,iron-recycling and re-utilization constitute important aspects of iron homeostasis. The cells responsible for efficiently recycling iron belong to the mononuclear phagocytic cells, which includes macrophages. One compartment in which tissue turnover is critical is the hematopoietic system. In the adult mouse, about 22 million lymphocytes are produced daily and, for their number to remain constant, an equal number of cells must die every day. However, practical and sensitive tools necessary to study temporal and spatial changes in tissue iron content are currently lacking. Overall, we aim to understand how cells and organisms regulate their iron content, and how distinct tissues coordinate iron distribution in response to altered iron homeostasis. We propose to unravel several essential aspects ofiron homeostasis: the regulation of cellular iron uptake and recycling, intestinal iron absorption, and brain iron metabolism. We expect that this fundamental research will make significant contributions to the field of iron biology and animal physiology. Because iron metabolism shares remarkable similarities in mammals and iron is essential for biological systems, the knowledge gained by studying iron metabolism in mice may very well become pertinent to more applied fields, such as human health and animal husbandry.