Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization
Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization
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DOI：
10.1126/science.1104742
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发表时间：
2004-12-17
期刊：
影响因子：
56.9
通讯作者：
Kaplan, J
中科院分区：
文献类型：
--
作者：
Nemeth, E;Tuttle, MS;Kaplan, J
铁调素是肝脏响应铁负荷和炎症而分泌的肽激素。铁调素减少会导致组织铁超负荷，而铁调素过量则会导致低铁血症和炎症性贫血。铁转运蛋白是一种存在于吸收性肠上皮细胞、巨噬细胞、肝细胞和胎盘细胞表面的铁输出蛋白。在这里，我们报告铁调素在组织培养细胞中与铁转运蛋白结合。结合后，铁转运蛋白被内化并降解，导致细胞铁输出减少。因此，铁调素对铁转运蛋白的翻译后调节可能完成一个稳态循环：铁调节铁调素的分泌，进而控制铁转运蛋白在细胞表面的浓度。
Hepcidin is a peptide hormone secreted by the liver in response to iron loading and inflammation. Decreased hepcidin leads to tissue iron overload, whereas hepcidin overproduction leads to hypoferremia and the anemia of inflammation. Ferroportin is an iron exporter present on the surface of absorptive enterocytes, macrophages, hepatocytes, and placental cells. Here we report that hepcidin bound to ferroportin in tissue culture cells. After binding, ferroportin was internalized and degraded, leading to decreased export of cellular iron. The posttranslational regulation of ferroportin by hepcidin may thus complete a homeostatic loop: Iron regulates the secretion of hepcidin, which in turn controls the concentration of ferroportin on the cell surface.