On the Mechanism of Iron-induced Synthesis of Apoferritin in HeLa Cells

The induction of ferritin was studied in suspension cultures of HeLa cells. New synthesis of apoferritin was assessed by the incorporation of 4 C-leucine into ferritin, the labeled protein being isolated from the cells by antibody precipitaion after a preliminary purification in the presence of carrier human ferritin. Apoferritin synthesis was found to be accelerated by incubation with iron salts, the effect being maximal throughout the concentration range of 10 to 100 fg of iron per ml. The stimulation was specific for ferritin as opposed to the general mixture of cell proteins, and was specific for iron among the heavy metal ions tested. The response to added iron was "immediate" in experiments that could have detected a 10-min lag. Bipyridyl largely prevented the stimulatory effect of iron, whereas deferoxamine prevented cellular uptake of iron and even removed much iron previously incorporated into cellular ferritin.