[Ferrochelatase gene expression in erythroid cells]

The mRNA level for ferrochelatase was assessed in the total cytoplasmic RNA isolated from mouse erythroleukaemic cells, line 707, in the course of induction of erythroid differentiation with hexamethylenebisacetamide and from spleen cells of mice in different stages of erythroid differentiation after phenylhydrazine administration. The level of this mRNA increased after five days of induction of erythroleukaemic cells about six times. An even more marked increase of the mRNA level for ferrochelatase (13.5X) was found in the total cytoplasmic RNA isolated from erythropoietic spleen cells of mice after induction of haemolytic anaemia by phenylhydrazine. Haem synthesis inhibitors (succinylacetone, isonicotinic acid hydrazide and penicillamine) caused a reduced gene expression for ferrochelatase in erythroleukaemic cells of mice induced with hexamethylenebisacetamide. Conversely addition of precursors of haem synthesis (5-aminolaevulinic acid or protoporphyrin IX) led to an increased mRNA synthesis for ferrochelatase. In addition to protoporphyrin synthesis the supply of another substrate, iron, is decisive for the gene expression ferrochelatase. Iron chelators (desferrioxamine or pyridoxal isonicotinoylhydrazone) reduced and iron donors (iron bound to transferrin or pyridoxal isonicotinoylhydrazone) enhanced mRNA synthesis for ferrochelatase. Added haemin reduces mRNA synthesis for ferrochelatase in fully induced erythroleukaemic cells but increases the gene expression ferrochelatase in the course of induction of erythroid differentiation because it acts as an inducing agent.