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A study of zinc transporter 1 and its role in Type 3 Haemochromatosis

Parkinson, Liza (2009) A study of zinc transporter 1 and its role in Type 3 Haemochromatosis. Honours thesis, Murdoch University.

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Hereditary haemochromatosis is an autosomal recessive disorder of iron metabolism, characterised by increased iron absorption and progressive iron accumulation particularly in the liver. It has been shown that hepatocytes can acquire iron in two forms; transferrin-bound iron (TBI) and non-transferrin-bound iron (NTBI)1. Known transporters of NTBI into the cell include DMT1 and ZIP14, and FPN is the only transporter known to export iron.

The aims of this study were to characterize the zinc transporter, ZnT-1 and determine whether it is involved in iron transport, specifically as an exporter.

There was a decrease in mRNA expression of the short untranslated isoform of ZnT-1 in double mutant (Hfe -/- and TfR2 Y245X) mouse liver, a trend also seen in TfR1 and Hamp. The long untranslated isoform, however, was significantly higher in the iron-deficient mice as was expression of TfR1 and Ferroportin. Iron and zinc efflux was measured in cells over-expressing ZnT-1 and control cells. There was no difference between over-expressed and control cells in iron efflux. However, at 60 min, over-expressed cells had significantly more zinc efflux than control cells. More zinc than iron was released from the cell.

The results of this study do not support the hypotheses that (i) ZnT-1 reduces intracellular cytoplasmic iron concentration by promoting efflux and 2 ZnT-1 is down-regulated in iron-loaded cells.

Item Type: Thesis (Honours)
Murdoch Affiliation: School of Biological Sciences and Biotechnology
Supervisor(s): Graham, Ross and Trinder, Debbie
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