Extracellular ferrireductase activity of K562 cells is coupled to transferrin-independent iron transport.
Abstract
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)
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Studies of non-transferrin bound iron uptake by cultured cells support the conclusion that other transmembrane iron importers exist.
“Studies of non-transferrin bound iron uptake by cultured cells support this conclusion.”
From Forging a field: the golden age of iron biology. (2008) · cites this paper as [68]
Cites
Erythroid transcription factor NF-E2 is a haematopoietic-specific basic–leucine zipper protein
Andrews, N. C., Erdjument‐Bromage, H., Davidson, M. B., Tempst, P., & Orkin, S. H. (1993) · Nature · doi:10.1038/362722a0 · Cited by 637 · see citing works
Transition Metals in Control of Gene Expression
O’Halloran, T. V. (1993) · Science · doi:10.1126/science.8342038 · Cited by 626 · see citing works
IRON ABSORPTION AND TRANSPORT IN MICROORGANISMS
Neilands, J. B. (1981) · Annual Review of Nutrition · doi:10.1146/annurev.nu.01.070181.000331 · Cited by 477 · see citing works
Transplasma-membrane redox systems in growth and development
Crane, F. L., SUN, I. L., Clark, M. G., Grebing, C., & Löw, H. (1985) · Biochimica et Biophysica Acta (BBA) - Reviews on Bioenergetics · doi:10.1016/0304-4173(85)90013-8 · Cited by 446 · see citing works
Genetic Evidence that Ferric Reductase Is Required for Iron Uptake in Saccharomyces cerevisiae
Dancis, A., Klausner, R. D., Hinnebusch, A. G., & Barriocanal, J. G. (1990) · Molecular and Cellular Biology · doi:10.1128/mcb.10.5.2294-2301.1990 · Cited by 304 · see citing works
A sensitive and simple method for determination of ferrocyanide
Avron, M., & Shavit, N. (1963) · Analytical Biochemistry · doi:10.1016/0003-2697(63)90149-0 · Cited by 272 · see citing works
Regulation of the transferrin-independent iron transport system in cultured cells.
Kaplan, J., Jordan, I., & Sturrock, A. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)49946-2 · Cited by 198 · see citing works
Characterization of a transferrin-independent uptake system for iron in HeLa cells.
Sturrock, A., Alexander, J. K., Lamb, J., Craven, C., & Kaplan, J. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)39745-5 · Cited by 178 · see citing works
Eide, D. J., Davis-Kaplan, S. R., Jordan, I., Sipe, D. M., & Kaplan, J. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)36753-5 · Cited by 172 · see citing works
The mechanism of receptor‐mediated endocytosis
Smythe, E., & WARREN, G. (1991) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1991.tb16424.x · Cited by 165 · see citing works
Mobilization of iron from endocytic vesicles. The effects of acidification and reduction.
Núñez, M. T., Gaete, V., Watkins, J. A., & Glass, J. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)39205-1 · Cited by 159 · see citing works
An ascorbate-mediated transmembrane-reducing system of the human erythrocyte.
Orringer, E. P., & Roer, M. E. S. (1979) · Journal of Clinical Investigation · doi:10.1172/jci109277 · Cited by 133 · see citing works
Investigation of a role for reduction in ferric iron uptake by mouse duodenum
Raja, K. B., Simpson, R. J., & Peters, T. J. (1992) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/0167-4889(92)90129-y · Cited by 124 · see citing works
Thorstensen, K., & Romslo, I. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)68384-x · Cited by 119 · see citing works
Inman, R. S., & Wessling‐Resnick, M. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)52906-9 · Cited by 113 · see citing works
Self-citationMembrane transport of non-transferrin-bound iron by reticulocytes
Morgan, E. H. (1988) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(88)90374-4 · Cited by 101 · see citing works
Teichmann, R., & Stremmel, W. (1990) · Journal of Clinical Investigation · doi:10.1172/jci114953 · Cited by 87 · see citing works
Ellem, K. A. O., & Kay, G. F. (1983) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(83)91814-4 · Cited by 77 · see citing works
Hepatocytes and reticulocytes have different mechanisms for the uptake of iron from transferrin.
Thorstensen, K. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)37467-2 · Cited by 75 · see citing works
Clark, M. G., Partick, E. J., Patten, G. S., et al. (1981) · Biochemical Journal · doi:10.1042/bj2000565 · Cited by 73 · see citing works
Thorstensen, K., & Aisen, P. (1990) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/0167-4889(90)90053-g · Cited by 66 · see citing works
Peters, L. L., Andrews, N. C., Eicher, E. M., Davidson, M. B., Orkin, S. H., & Lux, S. E. (1993) · Nature · doi:10.1038/362768a0 · Cited by 57 · see citing works
SUN, I. L., Crane, F. L., CHOU, J. Y., Löw, H., & Grebing, C. (1983) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(83)90402-3 · Cited by 49 · see citing works
Watkins, J. A., Altazan, J. D., Elder, P., Li, C. Y., Núñez, M. T., Cui, X. X., & Glass, J. (1992) · Biochemistry · doi:10.1021/bi00140a018 · Cited by 40 · see citing works
An NADH-diaphorase is located at the cell plasma membrane in a mouse neuroblastoma cell line NB41A3
Zurbriggen, R., & Dreyer, J.-L. (1994) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(94)90079-5 · Cited by 17 · see citing works
Plasma membrane dehydrogenases in rat brain synaptic membranes. Multiplicity and subunit composition
Dreyer, J.-L. (1990) · Journal of Bioenergetics and Biomembranes · doi:10.1007/bf00809067 · Cited by 10 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Fleming, M. D., Romano, M. A., Su, M. A., Garrick, L. M., Garrick, M. D., & Andrews, N. C. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.3.1148 · Cited by 936 · see citing works
Ohgami, R. S., Campagna, D. R., Greer, E. L., Antiochos, B., McDonald, A., Chen, J., Sharp, J. J., Fujiwara, Y., Barker, J. E., & Fleming, M. D. (2005) · Nature Genetics · doi:10.1038/ng1658 · Cited by 775 · see citing works
Forging a field: the golden age of iron biology.
Andrews, N. C. (2008) · Blood · doi:10.1182/blood-2007-12-077388 · Cited by 623 · see citing works
Gunshin, H., Fujiwara, Y., Custodio, A. O., DiRenzo, C., Robine, S., & Andrews, N. C. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24356 · Cited by 419 · see citing works
Anderson, G. J., & Vulpe, C. D. (2009) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-009-0051-1 · Cited by 317 · see citing works
Leishmania chagasi: uptake of iron bound to lactoferrin or transferrin requires an iron reductase
Wilson, M. E., Lewis, T. S., Miller, M. A., McCormick, M. L., & Britigan, B. E. (2002) · Experimental Parasitology · doi:10.1016/s0014-4894(02)00018-8 · Cited by 56 · see citing works
- Authors
- Inman, R. S., Coughlan, M. M., & Wessling-Resnick, M.
- Affiliations
- Harvard University (US)
- Venue
- Biochemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 1994-10-04
- Volume
- 33
- Issue
- 39
- Pages
- 11850-11857
- ISSN
- 0006-2960 (ISSN-L)
- 1520-4995
- OpenAlex
- W2060621718
- Cited by
- 70
- References
- 26
- Citations by year
- 2026: 1 · 2023: 1 · 2021: 1 · 2018: 1 · 2016: 2 · 2014: 1 · 2013: 1 · 2012: 1
- FWCI
- 2.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1r29dk045737-01, 5t32es007155-24)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK45737)
- National Institute of Environmental Health Sciences (NIEHS T32 ES07155)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Physical Sciences › Engineering › Mechanical Engineering › Iron and Steelmaking Processes
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Keywords
- ferrireductase, K562 cells, ferricyanide reduction, ferrocyanide, iron transport, enzyme kinetics, cadmium inhibition, insulin insensitivity, chemoresistance, erythroleukemia
- MeSH terms
- Biological Transport, Cadmium, Leukemia, Erythroblastic, Acute, Ferricyanides, Ferrocyanides, Humans, Insulin, Iron, Iron Radioisotopes, Kinetics, NADH, NADPH Oxidoreductases, Oxidation-Reduction, Transferrin, Tumor Cells, Cultured, Gene Expression Regulation, Enzymologic, FMN Reductase
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
