The iron-chelating agent picolinic acid enhances transferrin receptors expression in human erythroleukaemic cell lines.
Picolinic acid, a metal chelating molecule, was administered to human erythroleukaemic cell lines (K 562 and HEL) that were grown in serum-containing media. Picolinic acid inhibited both iron uptake and cell growth. Furthermore, picolinic acid was shown to markedly decrease the level of ferritin in the cells. In spite of the inhibition of cell growth, picolinic acid induced a marked increase in the transferrin-binding capacity of the cells. This phenomenon was due to a two-five-fold enhancement of the rate of transferrin receptor biosynthesis. Other iron-chelating compounds, capable of reducing the level of intracellular iron, also elicited a marked enhancement of the transferrin-binding capacity of the cells. However, the addition of iron, as ferric ammonium citrate, in the culture medium elicited a marked increase in the level of ferritin and a strong decrease in the transferrin-binding capacity of the cells. On the basis of these data we propose that a feed-back mechanism is involved in the regulation of transferrin receptors: when the cells accumulate iron they decrease the number of transferrin receptors in order to prevent further accumulation of iron; when no or low iron is available to the cells, the number of transferrin receptors markedly increases as a compensatory mechanism.
Testa
U
U
Louache
F
F
Titeux
M
M
Thomopoulos
P
P
Rochant
H
H
D002460:Cell Line; D005293:Ferritins / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism*; D010848:Picolinic Acids / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011990:Receptors, Transferrin; D013268:Stimulation, Chemical; D013997:Time Factors
D010848:Picolinic Acids; D011956:Receptors, Cell Surface; D011990:Receptors, Transferrin; D005293:Ferritins; D007501:Iron; C030614:picolinic acid