Intracellular heme coordinately modulates globin chain synthesis,
transferrin receptor number, and ferritin content in differentiating Friend
erythroleukemia cells
A Battistini, EM Coccia, G Marziali, D Bulgarini, S Scalzo, G Fiorucci, G Romeo, E Affabris, U Testa and GB Rossi
Department of Virology and Hematology, Istituto Superiore di Sanita, Rome,
Italy.
The effect of succinylacetone (SA), a highly specific inhibitor of ALA-
dehydratase and heme synthesis, on hemoglobin (Hb) production, transferrin
receptor (TfR), and ferritin expression was analyzed in differentiating
Friend leukemia cells (FLC). This compound exerted a pronounced inhibitory
effect not only on heme and Hb synthesis, but also on all the remaining
above-mentioned parameters. In particular, SA induced: (1) a reduction of
the level of alpha-globin mRNA; (2) a decreased number of exposed TfR
molecules, without modification of their affinity for the ligand; (3) a
reduced level of TfR RNA, without significant change of TfR gene
transcription rate; and (4) a lower ferritin content. The addition of
exogenous hemin to differentiating FLC exerted opposite effects, and
particularly induced an increase of both the number of TfRs and ferritin
content. These findings suggest that in erythroid cells optimal heme
synthesis is required to coordinately sustain globin chains synthesis and
TfR/ferritin production; thus, the intracellular heme level may represent a
key regulatory factor in the Hb synthesis pathway.
Volume 78,
Issue 8,
pp. 2098-2103,
10/15/1991
Copyright © 1991 by The American Society of Hematology
