Iron transport and subcellular distribution in Hep G2 hepatocarcinoma cells.
Thalassemic patients with iron overload are presently treated with deferoxamine or the experimental chelator deferiprone. To understand how these agents remove iron from the liver, cultured human hepatoma cells loaded with iron were previously used as a model for hepatic iron overload. The present study was undertaken to characterize further the pathways of iron transport and distribution in these cells. The activation energy for Fe2+ transport is 19 kJ/mol greater than for Fe3+, and the rate of Fe2+ transport--but not that of Fe3(+)--decreases with temperature above 25 degrees C, suggesting distinct uptake processes for different redox states of iron. Iron loading, which promotes a greater rate of Fe3+ transport, also caused a proportionally greater deposition of iron in the microsomal and cytosolic compartments and specifically lowered the activities of succinate-cytochrome c reductase and 5'-nucleotidase, representative markers of the mitochondria and plasma membrane, respectively. Both deferiprone and deferoxamine decreased total cellular iron and iron in each fraction except cytosol, indicating mobilization of iron for clearance from the cell via the cytosol. This model may be useful in characterizing the determinants of effective chelation in patients.
Department of Clinical Biochemistry, University of Toronto, Ontario, Canada.
J G
JG
Parkes
D M
DM
Templeton
D015720:5'-Nucleotidase / Q000187:drug effects / Q000378:metabolism; D006528:Carcinoma, Hepatocellular; D000077543:Deferiprone; D003676:Deferoxamine / Q000494:pharmacology; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D007501:Iron / Q000493:pharmacokinetics* / Q000494:pharmacology; D007502:Iron Chelating Agents / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms; D011728:Pyridones / Q000494:pharmacology; D013384:Succinate Cytochrome c Oxidoreductase / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured
D007502:Iron Chelating Agents; D011728:Pyridones; D000077543:Deferiprone; D007501:Iron; D013384:Succinate Cytochrome c Oxidoreductase; D015720:5'-Nucleotidase; D003676:Deferoxamine