Regulation of ferritin synthesis in macrophages by oxygen and a sulfhydryl-reactive agent

Ferritin synthesis is known to be regulated translationally by specific mRNA-protein interactions between an iron-responsive element (IRE) localized in the 5' untranslated region of ferritin mRNA and IRE-binding protein (IRE-BP). Binding of IRE-BP to IRE depresses its translation. In the present study, we demonstrated that ferritin synthesis in macrophages is strongly induced under hypoxic conditions by diethylmaleate, a sulfhydryl-reactive agent. The induction by diethylmaleate decreased as the oxygen tension rose. O2- is involved in this oxygen effect, because the induction was prevented when O2(-)-generating agents were present. Actinomycin D did not inhibit the ferritin synthesis induced by diethylmaleate under hypoxi. These results suggest that O2- is involved in post-transcriptional regulation of ferritin synthesis.