Essential but toxic: Controlling the flux of iron in the body
Essential but toxic: Controlling the flux of iron in the body
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DOI：
10.1111/j.1440-1681.2011.05661.x
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发表时间：
2012-08-01
影响因子：
2.9
通讯作者：
Wang, Fudi
中科院分区：
文献类型：
--
作者：
Anderson, Gregory J.;Wang, Fudi
铁是一种必需的营养物质，但是，由于铁过量是有毒的，所以它在体内的含量受到严格控制。这种调节是通过控制铁释放到血浆中来实现的。大多数铁从巨噬细胞进入血浆，巨噬细胞从衰老的红细胞中回收铁，但饮食铁的吸收和肝细胞储存铁的释放是其他主要来源。细胞铁输出是由膜铁转运蛋白铁转运蛋白1和铁氧化酶共同介导的。肝蛋白酶在肠道中提供这种氧化酶活性，而铜蓝蛋白是大多数其他组织使用的氧化酶。肝脏来源的肽hepcidin与铁转运蛋白1结合并将其从细胞表面移除，从而减少铁向血浆的供给量。反过来，hepcidin的水平反映了人体对铁的需求。在细胞水平上，铁转运蛋白1也可以通过缺氧诱导因子和铁调节蛋白独立于hepcidin调节。hepcidinroportin轴在调节机体铁稳态中起关键作用。
Iron is an essential nutrient, but, because it is toxic when present in excess, its levels in the body are tightly controlled. This regulation is affected by controlling the release of iron into the plasma. Most iron enters the plasma from macrophages, which recycle iron from senescent erythrocytes, but dietary iron absorption and the release of hepatocyte storage iron are other major sources. Cellular iron export is mediated by the membrane iron transporter ferroportin 1, in conjunction with an iron oxidase. Hephaestin provides this oxidase activity in the intestine, whereas ceruloplasmin is the oxidase used by most other tissues. The liver-derived peptide hepcidin binds to ferroportin 1 and removes it from the cell surface, thus reducing iron donation to the plasma. The levels of hepcidin, in turn, reflect body iron requirements. At the cellular level, ferroportin 1 can also be regulated independently of hepcidin by hypoxia-inducible factors and the iron regulatory proteins. The hepcidinferroportin axis plays a critical role in regulating body iron homeostasis.