Effect of aluminium on iron uptake and transferrin-receptor expression by human erythroleukaemia K562 cells.
Incubation of human erythroleukaemia K562 cells with Al-transferrin inhibited iron uptake from 59Fe-transferrin by about 80%. The inhibition was greater than that produced by a similar quantity of Fe-transferrin. Preincubation of cells for 6 h with either Al-transferrin or Fe-transferrin diminished the number of surface transferrin receptors by about 40% compared with cells preincubated with apo-transferrin. Al-transferrin did not compete significantly with Fe-transferrin for transferrin receptors and, when cells were preincubated for 15 min instead of 6 h, the inhibitory effect of Al-transferrin on receptor expression was lost. Both forms of transferrin also decreased the level of transferrin receptor mRNA by about 50%, suggesting a common regulatory mechanism. Aluminium citrate had no effect on iron uptake or transferrin-receptor expression. AlCl3 also had no effect on transferrin-receptor expression, but at high concentration it caused an increase in iron uptake by an unknown, possibly non-specific, mechanism. Neither Al-transferrin nor AlCl3 caused a significant change in cell proliferation. It is proposed that aluminium, when bound to transferrin, inhibits iron uptake partly by down-regulating transferrin-receptor expression and partly by interfering with intracellular release of iron from transferrin.
McGregor
S J
SJ
University Department of Bacteriology and Immunology, Western Infirmary, Glasgow, Scotland, U.K.
Naves
M L
ML
Oria
R
R
Vass
J K
JK
Brock
J H
JH
D000535:Aluminum / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007700:Kinetics; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics*; D011990:Receptors, Transferrin / Q000187:drug effects / Q000235:genetics*; D014168:Transferrin / Q000378:metabolism* / Q000494:pharmacology*
D012333:RNA, Messenger; D011990:Receptors, Transferrin; D014168:Transferrin; C066781:aluminum-transferrin; D000535:Aluminum; D007501:Iron