Characterization of Fe2+ and Fe3+ transport by iron-loaded cardiac myocytes.
Plasma iron overload causes cardiac iron accumulation leading to toxicity and organ failure. In order to understand the basis of iron acquisition, we examined mechanisms of Fe3+ and Fe2+ uptake in control and iron-loaded cardiomyocyte cultures. Iron loading increased rates of Fe3+ and Fe2+ uptake, primarily by increasing Vmax. Inhibition of Fe3+ transport by impermeable Fe2+ chelators and the presence of a cell surface ferricyanide reductase activity are consistent with a role for redox cycling in Fe3+ uptake. However, flavoproteins and copper-dependent oxidases known to be required for redox-active iron transport in yeast do not appear to be involved in iron uptake by cardiac myocytes, nor do the abundant cardiac L-type Ca2+ channels. The data suggest that both redox states of iron contribute to cardiac iron accumulation in iron overload.
Parkes
J G
JG
Department of Clinical Biochemistry, University of Toronto, Ontario, Canada.
Olivieri
N F
NF
Templeton
D M
DM
D000818:Animals; D000831:Animals, Newborn; D001692:Biological Transport; D015220:Calcium Channels / Q000502:physiology*; D002478:Cells, Cultured; D038181:FMN Reductase; D005290:Ferric Compounds / Q000378:metabolism*; D005296:Ferrous Compounds / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000503:physiopathology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D013816:Thermodynamics
D015220:Calcium Channels; D005290:Ferric Compounds; D005296:Ferrous Compounds; D007501:Iron; D038181:FMN Reductase; D009247:NADH, NADPH Oxidoreductases; C023903:ferric citrate iron reductase