Extracellular ferrireductase activity of K562 cells is coupled to transferrin-independent iron transport.
The reduction of Fe3+ to Fe2+ has been established to play a critical role in the uptake of iron by many organisms. Recently, a mechanism of iron transport in the absence of transferrin (Tf) was described for the human K562 cell line and a role for ferrireductase activity was implicated in this process as well [Inman, R. S., & Wessling-Resnick, M. (1993) J. Biol. Chem. 268, 8521-8528]. The present report characterizes the extracellular reduction of ferricyanide to ferrocyanide catalyzed by K562 cells. The observation that membrane-impermeant ferricyanide competitively inhibits Tf-independent assimilation of iron from 55Fe-nitriloacetic acid indicates that this ferrireductase activity is indeed coupled to the transport mechanism. From a series of initial rate experiments, the kinetic parameters for cell surface ferrireductase activity, Vmax = 0.102 nmol min-1 (10(6) cells)-1 and Km = 6.13 microM, were determined. Neither the Vmax nor the Km of this reaction is modulated by changes in extra- or intracellular iron levels; thus, similar to Tf-independent transport activity in K562 cells, the ferrireductase activity is not regulated in response to iron levels. Transmembrane oxidoreductase activity is also reportedly involved in the control of cellular growth; however, the K562 cell ferrireductase is unresponsive to insulin and is not inhibited by the antitumor drugs adriamycin, actinomycin D, or cis-platin, observations that fail to support a role for this particular activity in cell regulation. Rather, the K562 cell ferrireductase appears to be tightly coupled to the mechanism of Tf-independent transport as demonstrated by its sensitivity to Cd2+, a specific inhibitor of non-Tf iron uptake by K562 cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Inman
R S
RS
Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115.
Coughlan
M M
MM
Wessling-Resnick
M
M
D001692:Biological Transport / Q000187:drug effects; D002104:Cadmium / Q000494:pharmacology; D038181:FMN Reductase; D005292:Ferricyanides / Q000378:metabolism*; D005295:Ferrocyanides / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007501:Iron / Q000378:metabolism*; D007504:Iron Radioisotopes; D007700:Kinetics; D004915:Leukemia, Erythroblastic, Acute; D009247:NADH, NADPH Oxidoreductases / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D014168:Transferrin / Q000378:metabolism; D014407:Tumor Cells, Cultured
D005292:Ferricyanides; D005295:Ferrocyanides; D007328:Insulin; D007504:Iron Radioisotopes; D014168:Transferrin; D002104:Cadmium; C007931:hexacyanoferrate III; D007501:Iron; D038181:FMN Reductase; D009247:NADH, NADPH Oxidoreductases; C023903:ferric citrate iron reductase; C020354:hexacyanoferrate II