Aluminum alters iron and manganese uptake and regulation of surface transferrin receptors in primary rat oligodendrocyte cultures

Transferrin (Tf) is a major transport protein for both iron (Fe) and aluminum (Al), as well as manganese (Mn) and it can mediate cellular uptake of these elements via cell surface Tf receptors. To study the effect of AI-Tf on Tf receptor regulation, primary oligodendrocyte cultures were prepared from cortices of newborn rats. The effects of Al-Tf on Mn-54 and Fe-59 uptake were compared to those of apo-, Fe-, or Mn-Tf (1.25 mu M). To examine changes in cell surface Tf binding capacity, preincubation (4 h, 37 degrees C) was performed with apo-, Al- or Fe-Tf and homologous receptor binding studies were subsequently conducted with I-125-Fe-Tf at 4 degrees C. Incubation with Al-Tf, but not with equimolar amounts of Al chloride or Al citrate, led to dose-related increases in cellular Al. Incubation with either Al- or Fe-Tf decreased Fe-59 uptake, while incubation with either Al- or Mn-Tf decreased Mn-54 uptake. Surface Tf receptor sites/cell were 1.05, 0.60 and 0.46 x 10(5) after incubations with equivalent amounts of apo-, Fe-, and AI-Tf respectively. The data suggest that Al-Tf down-regulates surface Tf receptors on oligodendrocytes and can limit Fe and Mn uptake through this mechanism.