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首页> 外文期刊>Journal of Cellular Physiology >Increased IRP1 and IRP2 RNA binding activity accompanies a reduction of the labile iron pool in HFE-expressing cells.
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Increased IRP1 and IRP2 RNA binding activity accompanies a reduction of the labile iron pool in HFE-expressing cells.

机译：增加IRP1 IRP2 RNA结合的活动伴随减少不稳定铁池在HFE-expressing细胞。

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摘要

Iron regulatory proteins (IRPs), the cytosolic proteins involved in the maintenance of cellular iron homeostasis, bind to stem loop structures found in the mRNA of key proteins involved iron uptake, storage, and metabolism and regulate the expression of these proteins in response to changes in cellular iron needs. We have shown previously that HFE-expressing fWTHFE/tTA HeLa cells have slightly increased transferrin receptor levels and dramatically reduced ferritin levels when compared to the same clonal cell line without HFE (Gross et al., 1998, J Biol Chem 273:22068-22074). While HFE does not alter transferrin receptor trafficking or non-transferrin mediated iron uptake, it does specifically reduce (55)Fe uptake from transferrin (Roy et al., 1999, J Biol Chem 274:9022-9028). In this report, we show that IRP RNA binding activity is increased by up to 5-fold in HFE-expressing cells through the activation of both IRP isoforms. Calcein measurements show a 45% decrease in the intracellular labile iron pool in HFE-expressing cells, which is in keeping with the IRP activation. These results all point to the direct effect of the interaction of HFE with transferrin receptor in lowering the intracellular labile iron pool and establishing a new set point for iron regulation within the cell.
机译：铁调节蛋白(irp),胞质蛋白参与细胞的维护铁内稳态,绑定到茎环结构发现关键蛋白mRNA的铁摄取、储存和代谢和调节这些蛋白的表达在回应改变细胞铁的需求。此前,HFE-expressing fWTHFE / tTA海拉细胞转铁蛋白略有增加受体水平,极大地降低了铁蛋白水平相比,相同的克隆细胞系没有HFE(总et al ., 1998, J临床生物化学273:22068 - 22074)。转铁蛋白受体贩卖或non-transferrin介导的铁吸收特别是减少(55)铁吸收转铁蛋白(Roy et al ., 1999, J临床生物化学274:9022 - 9028)。核糖核酸绑定活动增加了5倍在HFE-expressing细胞的激活IRP亚型。减少45%的细胞内不稳定的铁池HFE-expressing细胞,它是一致的IRP激活。的直接影响HFE之间的交互转铁蛋白受体在降低细胞内不稳定铁池和建立新设置点铁监管中细胞。

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