Show simple item record

dc.contributor.authorHamdi, Amel
dc.contributor.authorSchranzhofer, Matthias
dc.contributor.authorLok, Nam-Chun
dc.contributor.authorSantos, Daniel Garcia
dc.contributor.authorPonka, Prem
dc.identifier.citationHamdi, A., Schranzhofer, M., Lok, N. C., Garcia-Santos, D., & Ponka, P. (2014). Transcriptional regulation of transferrin receptor by heme in erythroid cells. Experimental Hematology, 42(8), S37.en_US
dc.description.abstractHemoglobin synthesis consumes most of the iron that is taken up by cells from plasma transferrin, and this process requires very high expression of transferrin receptors (TfR) at the membranes of erythroid cells. In contrast to other cells, developing red blood cells (RBC) regulate TfR expression not only at the level of mRNA stability via the iron regulatory proteins (IRP) 1 and 2, but also by transcription (Lok & Ponka, J Biol Chem 275:24185-90, 2000). Our laboratory studies provide evidence that TfR expression and cellular uptake of iron from Tf is stimulated by enhanced heme synthesis. Incubation of murine erythroleukemia (MEL) cells with 5-aminolevulinic acid (ALA) increased TfR expression as well as iron incorporation into heme. This effect of ALA can be completely prevented by the inhibitors of heme biosynthesis (succinylacetone [blocks ALA dehydratase] or N-methylprotoporphyrin [blocks ferrochelatase]), indicating that the effect of ALA requires its metabolism to heme. The induction of TfR mRNA expression by ALA is mainly a result of increased mRNA synthesis since the effect of ALA can be abolished by actinomycin D. Recently, IRP2 was proposed to play a role in maintaining TfR mRNA stability in developing RBC (Cooperman et al., Blood 106:1084-91; 2005; Galy et al., Blood 106: 2580-9, 2005). Importantly, we have demonstrated that ALA added to cultures of erythroid cells derived from IRP2 knock out mice restores the expression of TfR to levels observed in cells obtained from wild type mice. In conclusion, our results indicate that in erythroid cells heme serves as a positive feedback regulator that maintains high TfR levels thus ensuring adequate iron availability for hemoglobin synthesis.en_US
dc.subjectErythroid cellsen_US
dc.subjectPlasma transferrinen_US
dc.titleTranscriptional regulation of transferrin receptor by heme in erythroid cellsen_US
dc.title.alternativeJournal Articleen_US

Files in this item


There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record