Iron prevents ferritin turnover in hepatic cells.
It has long been assumed that iron regulates the turnover of ferritin, but evidence for or against this idea has been lacking. This issue was addressed using rat hepatoma cells with characteristics of hepatocytes subjected to a continuous influx of iron. Iron-pretreated cells were pulsed with [(35)S]Met for 60 min or with (59)Fe overnight and harvested up to 30 h thereafter, during which they were/were not cultured with ferric ammonium citrate (FAC; 180 microm). Radioactivity in ferritin/ferritin subunits of cell heat supernatants was determined by autoradiography of rockets obtained by immunoelectrophoresis or after precipitation with ferritin antibody and SDS-PAGE. Both methods gave similar results. During the +FAC chase, the concentration of ferritin in the cells increased linearly with time. Without FAC, the half-life of (35)S-ferritin was 19-20 h; with FAC there was no turnover. Without FAC, the iron in ferritin had an apparent half-life of 20 h; in the presence of FAC there was no loss of (59)Fe. Without FAC, concentrations of ferritin iron and protein also decreased in parallel. We conclude that a continuous influx of excess iron can completely inhibit the degradation of ferritin protein and that the iron and protein portions of ferritin molecules may be coordinately degraded.
Truty
J
J
Department of Chemistry and Biochemistry and Institute for Molecular Biology, California State University, Fullerton, California 92834-6866, USA.
Malpe
R
R
Linder
M C
MC
D000818:Animals; D001345:Autoradiography; D006528:Carcinoma, Hepatocellular; D003676:Deferoxamine / Q000494:pharmacology; D005290:Ferric Compounds / Q000494:pharmacology*; D005293:Ferritins / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D007122:Immunoelectrophoresis / Q000379:methods; D007501:Iron / Q000378:metabolism / Q000494:pharmacology*; D007502:Iron Chelating Agents / Q000494:pharmacology; D007504:Iron Radioisotopes / Q000378:metabolism; D011233:Precipitin Tests; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D051381:Rats; D014407:Tumor Cells, Cultured
D005290:Ferric Compounds; D007502:Iron Chelating Agents; D007504:Iron Radioisotopes; D000644:Quaternary Ammonium Compounds; D005293:Ferritins; D007501:Iron; D003676:Deferoxamine; C013531:ferric ammonium citrate