Effects of hyperoxia and iron on iron regulatory protein-1 activity and the ferritin synthesis in mouse peritoneal macrophages

Biochim Biophys Acta. 2001 Jan 12;1544(1-2):370-7. doi: 10.1016/s0167-4838(00)00251-x.

Abstract

Ferritin is an intracellular iron storage protein and its translation is inhibited by binding of iron regulatory proteins (IRPs) to the iron-responsive element (IRE) located in the 5' untranslated region of its mRNA. In this paper, we have investigated the effect of hyperoxia and iron on the binding activity of IRP-1 and the ferritin synthesis in mouse peritoneal macrophages. The binding activity of IRP-1 was increased and the ferritin synthesis was suppressed when the macrophages were cultured under hyperoxia, and the reverse occurred under hypoxia. Iron diminished the IRP-1-binding activity and the enhanced synthesis of ferritin. However, this effect was arrested under hyperoxia. Consistently, hypoxia-induced loss of binding activity of IRP-1 and the enhanced synthesis of ferritin were blocked in the presence of an iron chelator deferoxamine. These alterations of the binding activity of IRP-1 in response to oxygen and iron were not reproduced in the cell-free extract. The data suggest that in the macrophages oxygen and iron inversely act on the binding activity of IRP-1 and the ferritin synthesis, and that intracellular mechanism(s) to sense iron and/or oxygen is required for these actions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Ferritins / biosynthesis*
  • Hyperoxia / metabolism*
  • Iron / metabolism*
  • Iron Regulatory Protein 1
  • Iron-Regulatory Proteins
  • Iron-Sulfur Proteins / metabolism*
  • Macrophages, Peritoneal / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Oxidative Stress
  • RNA-Binding Proteins / metabolism*

Substances

  • Iron-Regulatory Proteins
  • Iron-Sulfur Proteins
  • RNA-Binding Proteins
  • Ferritins
  • Iron
  • Iron Regulatory Protein 1