Kamiya K
Third Department of Internal Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Hokkaido Igaku Zasshi. 1996 Jan;71(1):81-93.
The modulation of cellular iron metabolism depends on the expression of ferritin and transferrin receptor (TfR). These proteins are regulated post-transcriptionally by interaction of specific sequences, termed iron responsive elements (IRE) which are located in the 5' untranslated region (UTR) of ferritin mRNA and 3'UTR of TfR mRNA and a specific cytosolic protein, termed iron responsive element-binding protein (IRE-BP). The liver plays an important role in iron metabolism as a major organ of iron storage. In hepatocytes iron is taken up in the form of transferrin and intercellular iron levels are regulated by IRE/IRE-BP interaction. In spite of the important role of IRE/IRE-BP interaction, the role of it for proliferation and differentiational change in hepatoma cells is not well known. In this study, the author has investigated IRE/IRE-BP interaction and its target protein expression during proliferation and differentiational change of human hepatoblastoma cells (HepG2). This study revealed that the binding activity of IRE-BP to IRE was increased when HepG2 cells were cultured with an iron-chelating agent, deferoxamine (4.5 microM), and it was decreased when cultured with transferrin (100 micrograms/ml) during both proliferation and differentiational change induced by sodium butyrate. Also, the change of TfR expression was correlated with that of IRE-BP. These findings suggest that IRE/IRE-BP interaction may play an important role in the expression of TfR and cellular iron metabolism during proliferation and differentiational change of HepG2 cells.
细胞铁代谢的调节取决于铁蛋白和转铁蛋白受体(TfR)的表达。这些蛋白质通过特定序列的相互作用在转录后受到调节,这些特定序列称为铁反应元件(IRE),它们位于铁蛋白mRNA的5'非翻译区(UTR)和TfR mRNA的3'UTR中,以及一种特定的胞质蛋白,称为铁反应元件结合蛋白(IRE-BP)。肝脏作为铁储存的主要器官,在铁代谢中起重要作用。在肝细胞中,铁以转铁蛋白的形式被摄取,细胞内铁水平通过IRE/IRE-BP相互作用来调节。尽管IRE/IRE-BP相互作用具有重要作用,但其在肝癌细胞增殖和分化变化中的作用尚不清楚。在本研究中,作者研究了人肝母细胞瘤细胞(HepG2)增殖和分化变化过程中的IRE/IRE-BP相互作用及其靶蛋白表达。该研究表明,当HepG2细胞用铁螯合剂去铁胺(4.5 microM)培养时,IRE-BP与IRE的结合活性增加,而在丁酸钠诱导的增殖和分化变化过程中用转铁蛋白(100微克/毫升)培养时,结合活性降低。此外,TfR表达的变化与IRE-BP的变化相关。这些发现表明,IRE/IRE-BP相互作用可能在HepG2细胞增殖和分化变化过程中TfR的表达和细胞铁代谢中起重要作用。