Zip14 expression in hepatic iron overload

Abstract

The liver can acquire iron from plasma transferrin bound to the transferrin receptor (TfR) or from non-transferrin-bound iron (NTBI). During iron overload, hepatic TfR levels decrease whereas plasma NTBI levels increase, resulting in the accretion of NTBI in the liver. The molecular mechanisms responsible for hepatic NTBI uptake are poorly defined, but may involve Zip14, which has been shown to transport NTBI in AML12 cells, a mouse hepatocyte cell line (Liuzzi et al., PNAS, 2006). To explore this possibility further, we examined hepatic Zip14 mRNA levels in hypotransferrinemic (Trfhpx/hpx) mice that lack circulating transferrin but accumulate massive amounts of iron in the liver. Quantitative RT-PCR revealed no differences in levels of Zip14 transcripts (both long and short isoforms) between Trfhpx/hpx mice and controls (n=10/group). Similarly, treatment of AML12 hepatocytes with 0, 50, 250 or 500 μM of ferric nitrilotriacetate for 24 h had no effect on Zip14 mRNA levels, although TfR mRNA levels decreased by 75%. Collectively, these results suggest that Zip14 continues to be expressed during iron overload, and may thus contribute to NTBI uptake into the liver. Funded by NIH grant DK065064.