McGregor S J, Naves M L, Oria R, Vass J K, Brock J H
University Department of Bacteriology and Immunology, Western Infirmary, Glasgow, Scotland, U.K.
Biochem J. 1990 Dec 1;272(2):377-82. doi: 10.1042/bj2720377.
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.
用人转铁蛋白（Al-转铁蛋白）孵育人红白血病K562细胞，可使59Fe-转铁蛋白的铁摄取减少约80%。这种抑制作用比等量的铁转铁蛋白产生的抑制作用更强。与用脱铁转铁蛋白预孵育的细胞相比，用Al-转铁蛋白或铁转铁蛋白预孵育细胞6小时，表面转铁蛋白受体数量减少约40%。Al-转铁蛋白与铁转铁蛋白在转铁蛋白受体上的竞争不明显，并且当细胞预孵育15分钟而非6小时时，Al-转铁蛋白对受体表达的抑制作用消失。两种形式的转铁蛋白还使转铁蛋白受体mRNA水平降低约50%，提示存在共同的调节机制。柠檬酸铝对铁摄取或转铁蛋白受体表达无影响。AlCl3对转铁蛋白受体表达也无影响，但在高浓度时，它通过一种未知的、可能是非特异性的机制导致铁摄取增加。Al-转铁蛋白和AlCl3均未引起细胞增殖的显著变化。有人提出，铝与转铁蛋白结合时，部分通过下调转铁蛋白受体表达、部分通过干扰转铁蛋白中铁的细胞内释放来抑制铁摄取。
