Kuriyama-Matsumura K, Sato H, Yamaguchi M, Bannai S
Department of Biochemistry, University of Tsukuba, Ibaraki, Japan.
Biochem Biophys Res Commun. 1998 Aug 10;249(1):241-6. doi: 10.1006/bbrc.1998.9046.
Ferritin is an intracellular iron storage protein whose synthesis is regulated post-transcriptionally by a mechanism that involves binding of cytoplasmic iron regulatory protein (IRP) to iron-responsive element (IRE) in the 5' untranslated region of ferritin mRNA. In this study, we have shown that in mouse peritoneal macrophages, the synthesis of ferritin was enhanced and the IRE binding activity of IRP-1 was diminished when the oxygen tension was decreased. Iron is known to induce ferritin synthesis and even in the presence of a low concentration of iron, synthesis of ferritin was enhanced and the activity of IRP-1 was decreased under hypoxia. The enhanced synthesis of ferritin under hypoxia was abolished by the addition of O2(-)-generating agents but not H2O2. The decreased activity of IRP-1 under hypoxia was reversed by adding O2(-)-generating agents. These data suggest that O2- generated in the cell is involved in alterations of ferritin synthesis and the activity of IRP-1 by oxygen.
铁蛋白是一种细胞内铁储存蛋白，其合成在转录后受到一种机制的调控，该机制涉及细胞质铁调节蛋白（IRP）与铁蛋白mRNA 5'非翻译区的铁反应元件（IRE）结合。在本研究中，我们发现，在小鼠腹腔巨噬细胞中，当氧张力降低时，铁蛋白的合成增强，IRP-1的IRE结合活性降低。已知铁可诱导铁蛋白合成，即使在低浓度铁存在的情况下，缺氧时铁蛋白的合成仍会增强，且IRP-1的活性会降低。缺氧时铁蛋白合成的增强可被添加产生活性氧（O2-）的试剂所消除，但不能被过氧化氢（H2O2）消除。添加产生活性氧（O2-）的试剂可逆转缺氧时IRP-1活性的降低。这些数据表明，细胞内产生的O2-参与了氧对铁蛋白合成和IRP-1活性的改变。
