Regulation Of Transferrin Receptor Expression In Erythroid Cells And Its Clinical Application In The Diagnosis Of Anemia,

All cells have to adjust uptake, utilization and storage of iron according to the availability and their requirement for this essential metal. Transferrin receptor (TfR) which is a membrane receptor plays a key role in the control of iron uptake following requirement for specific cellular functions. In proliferating non-erythroid cells, the expression of TfR is negatively regulated by the amount of intracellular iron. Fe-dependent regulation of TfR occurs post-transcriptionally and is mediated by iron responsive elements (IRE) located in the 3' untranslated region of the TfR mRNA. IREs are recognized by a specific cytoplasmic binding protein iron regulatory factor (IRE) that, in the absence of Fe, binds with high affinity to TfR mRNA, preventing its degradation. While TfR numbers are positively correlated with proliferation in non-erythroid, TfR numbers in hemoglobin-synthesizing cells increase during differentiation and are, therefore, negatively correlated with proliferation. This suggests a distinct regulation of erythroid TfR expression. Erythroid cells require a large amount of iron for hemoglobin synthesis. These cells have aboundant TfR on their surface to receive iron from transferrin by receptor-mediated endocytosis.In the present study, we studied changes of TfR mRNA levels, with Northern blot, under the condition of different iron status and heme-synthesizing in non-induced and induced K562 cells with DMSO. These results are: (l)When cells proliferate, TfR mRNA levels increase in non-induced K562 cells. In induced K562 cells, although cells stop proliferating, because of heme-synthesizing, TfR mRNA levels increase, too. (2)The amount of intracellular iron regulates TfR mRNA expression in non-induced and induced K562 cells:when iron is in excess, (added transferrin to the cultural liquid), TfR mRNA levels decrease; when iron is in deficiency ( added deferrioxamine or Anti-TfR MoAb to the cultural liquid), TfR mRNA levels increase. Changeable degree of TfR mRNA levels regulated by intracellular iron in non-induced cells is higher than in induced cells. (3) In induced cells, Inhibition of...