Diferric transferrin regulates transferrin receptor 2 protein stability
Diferric transferrin regulates transferrin receptor 2 protein stability
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DOI：
10.1182/blood-2004-06-2477
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发表时间：
2004-12-15
期刊：
影响因子：
20.3
通讯作者：
Enns, CA
中科院分区：
文献类型：
--
作者：
Johnson, MB;Enns, CA
转铁蛋白受体2(TfR2)是一种在肝细胞中表达的与铁结合转铁蛋白(Tf)结合的2型跨膜蛋白。TfR2的突变会导致一种形式的遗传性血色素沉着症，这种疾病过度吸收膳食中的铁可导致肝硬变、糖尿病、关节炎和心力衰竭。TfR2在铁稳态中的作用尚不清楚。我们研究了TfR2在HepG2细胞中的调节作用。Western印迹分析表明，加入二铁Tf后，TfR2的表达呈时间和剂量依赖性增加。在暴露于二铁转铁蛋白的细胞中，TfR2的量在从培养液中去除二铁转铁蛋白后的8小时内恢复到对照水平。然而，当非Tf结合铁(Fenta)或apo Tf加入到介质中时，TfR2不会增加。对二铁转铁蛋白的反应似乎是肝细胞特异性的。实时定量逆转录-聚合酶链式反应(qRT-PCR)分析表明，TfR2的mRNA水平在暴露于不同铁基转移因子的细胞中没有变化。相反，TfR2的增加归因于暴露于二铁Tf的细胞中TfR2蛋白半衰期的增加。我们的结果支持TfR2通过感知二铁转铁蛋白浓度的变化来监测铁水平的作用。(C)2004年，由美国血液病学会提供。
Transferrin receptor 2 (TfR2) is a type 2 transmembrane protein expressed in hepatocytes that binds iron-bound transferrin (Tf). Mutations in TfR2 cause one form of hereditary hemochromatosis, a disease in which excessive absorption of dietary iron can lead to liver cirrhosis, diabetes, arthritis, and heart failure. The function of TfR2 in iron homeostasis is unknown. We have studied the regulation of TfR2 in HepG2 cells. Western blot analysis shows that TfR2 increases in a time- and dose-dependent manner after diferric Tf is added to the culture medium. In cells exposed to diferric Tf, the amount of TfR2 returns to control levels within 8 hours after the removal of diferric Tf from the medium. However, TfR2 does not increase when non-Tf-bound iron (FeNTA) or apo Tf is added to the medium. The response to diferric Tf appears to be hepatocyte specific. Real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis shows that TfR2 mRNA levels do not change in cells exposed to diferric Tf. Rather, the increase in TfR2 is attributed to an increase in the half-life of TfR2 protein in cells exposed to diferric Tf. Our results support a role for TfR2 in monitoring iron levels by sensing changes in the concentration of diferric Tf. (C) 2004 by The American Society of Hematology.