Ferric citrate uptake by cultured rat hepatocytes is inhibited in the presence of transferrin

Ross Graham, Evan Morgan, Erica Baker

Research output: Contribution to journalArticlepeer-review

26 Citations (Web of Science)

Abstract

Diseases associated with iron overload occur worldwide. In subjects suffering from these conditions, transferrin is likely to be fully saturated and excess plasma iron must be complexed to other molecules. Consequently, the liver, which is the major site of iron storage, will be presented with iron in both transferrin-bound and non-transferrin-bound forms and these forms may compete for uptake by hepatocytes. The endogenous low-molecular-mass iron chelator, citrate, is considered to be a major contributing molecule to non-transferrin iron transport. This study was conducted to investigate the effects of transferrin on the uptake of citrate and iron citrate by hepatocytes in culture. Rat hepatocytes were incubated with 100 mu M [C-14]citrate and 1.0 mu M Fe-55 in the presence or absence of various forms of transferrin. Binding and internalisation of both citrate and iron were inhibited in a dose-dependent manner with increasing concentration of diferric transferrin, with iron uptake decreasing to less than 5% of control values. Apotransferrin was markedly more effective in blocking citrate and iron uptake, reaching the same levels of inhibition at a 15-fold lower concentration of protein. The binding of citrate to the cell membrane was not affected significantly by changing the iron saturation of transferrin but internalisation decreased with decreasing saturation. In contrast, both the binding and internalisation of iron decreased with decreasing saturation. Incubations carried out using Fe-55-labelled citrate in the presence of Fe-59-labelled diferric transferrin indicated that citrate-mediated iron binding by the cells decreased with increasing diferric transferrin concentrations but the citrate iron was not replaced by iron from transferrin during the 15-min incubation period. Instead, total iron uptake decreased. These data suggest that citrate-mediated iron uptake by hepatocytes shares at least one common pathway with transferrin-mediated iron uptake.
Original languageEnglish
Pages (from-to)139-145
JournalEuropean Journal of Biochemistry
Volume253
DOIs
Publication statusPublished - 1998

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