Regulation of ferritin synthesis and iron regulatory protein 1 by oxygen in mouse peritoneal macrophages

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.