Regulation of the transferrin-independent iron transport system in cultured cells.
Open accessAbstract
Mammalian cells accumulate iron via the binding of transferrin to high affinity surface receptors, or through a transferrin-independent pathway which involves the uptake of iron-organic anion chelates by a membrane-based transport system. Previously we determined that the transferrin-independent transport system was present on a wide variety of cultured cells (Sturrock, A., Alexander, J., Lamb, J., Craven, C. M., and Kaplan, J. (1990) J. Biol. Chem. 265, 3139-3145). In this communication we demonstrate that the transferrin-independent iron uptake system is regulated differently than the transferrin-mediated pathway. The activity of the transferrin-independent system was unaffected by changes in cellular growth rate, induction of DNA synthesis and cell division, or depletion of cellular iron. Exposure of cells to ferric or ferrous iron, however, resulted in a time-dependent increase in transport activity, due to a change in Vmax with no change in Km. Increased transport activity was seen in a variety of cultured cell types, occurred in the presence of cycloheximide, and persisted for hours after removal of iron. The ability of other transition metals to induce changes in transport, or to compete with iron for accumulation by the transferrin-independent uptake system, was critically dependent on the composition of the media in which the cells were incubated. Metals such as Cu2+ or Zn2+, but not Cd2+ or Mn2+, when dissolved in a balanced salt solution buffered with 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid, induced changes in the transferrin-independent iron transport system. The same metals which induced changes in transport were ineffective in media containing amino acids, ascorbate, or N-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]glycine. The Vmax of the transferrin-independent iron transport system was also elevated by increases in intracellular Ca2+. The effect of iron on transport activity, however, did not result from an iron-induced release of intracellular Ca2+. These results suggest a novel form of regulation in which the presence of extracellular iron induces the appearance of previously cryptic transporters and thus accelerates the clearance of potentially toxic molecules.
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 [69]
Cites
PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENT
Lowry, O. H., Rosebrough, N., Farr, A. L., & Randall, R. (1951) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)52451-6 · Cited by 315,771 · see citing works
A new generation of Ca2+ indicators with greatly improved fluorescence properties.
Grynkiewicz, G., Poenie, M., & Tsien, R. Y. (1985) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)83641-4 · Cited by 21,722 · see citing works
Non-transferrin-bound iron in plasma or serum from patients with idiopathic hemochromatosis
Grootveld, M. C., Bell, J. D., Halliwell, B. B., Aruoma, O. I., Bomford, A. B., & Sadler, P. J. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)83758-9 · Cited by 404 · see citing works
Growth factors immediately raise cytoplasmic free Ca2+ in human fibroblasts.
Moolenaar, W. H., Tertoolen, L. G. J., & de Laat, S. W. (1984) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)39690-4 · Cited by 392 · see citing works
Modulation of cell surface iron transferrin receptors by cellular density and state of activation
Larrick, J. W., & Cresswell, P. (1979) · Journal of Supramolecular Structure · doi:10.1002/jss.400110415 · Cited by 362 · see citing works
Craven, C. M., Alexander, J., Eldridge, M., Kushner, J. P., Bernstein, S., & Kaplan, J. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.10.3457 · Cited by 259 · see citing works
Self-citationBrissot, P., Wright, T. L., L, W., & Weisiger, R. A. (1985) · Journal of Clinical Investigation · doi:10.1172/jci112125 · Cited by 251 · see citing works
Koeller, D. M., Casey, J. L., Hentze, M. W., Gerhardt, E. M., Chan, L.-N. L., Klausner, R. D., & Harford, J. B. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.10.3574 · Cited by 242 · see citing works
Noncoding 3′ sequences of the transferrin receptor gene are required for mRNA regulation by iron.
Owen, D., & Kühn, L. C. (1987) · The EMBO Journal · doi:10.1002/j.1460-2075.1987.tb02366.x · Cited by 223 · see citing works
Cadmium evokes inositol polyphosphate formation and calcium mobilization
Smith, J. B., Dwyer, S. D., & Smith, L. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)83208-2 · Cited by 212 · see citing works
Characterization of non-transferrin-bound iron clearance by rat liver.
Wright, T. L., Brissot, P., L, W., & Weisiger, R. A. (1986) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)67473-3 · Cited by 196 · see citing works
Regulation of HeLa cell transferrin receptors.
Ward, J. H., Kushner, J. P., & Kaplan, J. (1982) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)34022-5 · Cited by 182 · see citing works
Dadone, M. M., Kushner, J. P., Edwards, C. Q., Bishop, D. T., & Skolnick, M. H. (1982) · American Journal of Clinical Pathology · doi:10.1093/ajcp/78.2.196 · Cited by 178 · 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
Internalization and subcellular localization of transferrin and transferrin receptors in HeLa cells.
Lamb, J. E., Ray, F., Ward, J. H., Kushner, J. P., & Kaplan, J. (1983) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)32120-3 · Cited by 175 · see citing works
Evidence that transferrin supports cell proliferation by supplying iron for DNA synthesis
Laskey, J. D., Webb, I. J., Schulman, H. M., & Ponka, P. (1988) · Experimental Cell Research · doi:10.1016/0014-4827(88)90123-1 · Cited by 145 · see citing works
Transcriptional Regulation by Iron of the Gene for the Transferrin Receptor
Rao, K., Harford, J. B., Rouault, T. A., McClelland, A., Ruddle, F. H., & Klausner, R. D. (1986) · Molecular and Cellular Biology · doi:10.1128/mcb.6.1.236 · Cited by 128 · see citing works
The Gastrointestinal Tract and Iron Absorption
Wheby, M. S., Crosby, W. H., Merrill, B., & Lawson, N. (1963) · Blood · doi:10.1182/blood.v22.4.416.416 · Cited by 123 · see citing works
Determination of Serum Copper and Iron in a Single Small Sample
Landers, J. W., & Zak, B. (1958) · American Journal of Clinical Pathology · doi:10.1093/ajcp/29.6_ts.590 · Cited by 121 · see citing works
Heme regulation of HeLa cell transferrin receptor number.
Ward, J. H., Jordan, I., Kushner, J. P., & Kaplan, J. (1984) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)90683-6 · Cited by 112 · see citing works
Transferrin receptors of human fibroblasts. Analysis of receptor properties and regulation
Ward, J. H., Kushner, J. P., & Kaplan, J. (1982) · Biochemical Journal · doi:10.1042/bj2080019 · Cited by 75 · see citing works
Iron-induced L1210 cell growth: evidence of a transferrin-independent iron transport.
Basset, P., Quesneau, Y., & Zwiller, J. (1986) · PubMed · Cited by 75 · 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
Non-transferrin-bound iron uptake by rat liver. Role of membrane potential difference.
Wright, T. L., Fitz, J., & Weisiger, R. A. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)77953-8 · Cited by 57 · see citing works
Isolation of mouse transferrin using salting-out chromatography on sepharose CL-6B
Sawatzki, G., Anselstetter, V., & Kubanek, B. (1981) · Biochimica et Biophysica Acta (BBA) - Protein Structure · doi:10.1016/0005-2795(81)90073-8 · Cited by 29 · see citing works
The Promoter Region of the Human Transferrin Receptor Gene
Casey, J. L., Jeso, B. D., Rao, K., Rouault, T. A., Klausner, R. D., & Harford, J. B. (1988) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1988.tb55492.x · Cited by 15 · 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
The Evolution of Iron Chelators for the Treatment of Iron Overload Disease and Cancer
Kalinowski, D. S., & Richardson, D. R. (2005) · Pharmacological Reviews · doi:10.1124/pr.57.4.2 · Cited by 721 · see citing works
“…endocytosis remains the major pathway of iron uptake, cells can also internalize iron from small molecular weight complexes such as ferric citrate through a membrane-based iron transport system (Sturrock et al., 1990; Kaplan et al., 1991; Richardson and Baker, 1991; Richardson and Ponka, 1995).”
BackgroundNon-transferrin bound iron: a key role in iron overload and iron toxicity
Brissot, P., Ropert, M., Le Lan, C., & Loréal, O. (2012) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2011.07.014 · Cited by 654 · see citing works
“Using transformed cell lines (fibroblasts [23], HepG2 cells [24]) intracellular iron loading led to an increased NTBI uptake.”
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
“The non–transferrin-bound iron transport system appears to require reduction of Fe3+ to Fe2+ by an extracellular ferrireductase (10, 11, 30).”
BackgroundThe FET4 gene encodes the low affinity Fe(II) transport protein of Saccharomyces cerevisiae
Dix, D., Bridgham, J. T., Broderius, M. A., Byersdorfer, C. A., & Eide, D. J. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)47163-3 · Cited by 320 · see citing works
The importance of non-transferrin bound iron in disorders of iron metabolism
Breuer, W., Hershko, C., & Cabantchik, Z. I. (2000) · Transfusion Science · doi:10.1016/s0955-3886(00)00087-4 · Cited by 268 · see citing works
Cooksey, R. C., Jouihan, H. A., Ajioka, R. S., Hazel, M. W., Jones, D. L., Kushner, J. P., & McClain, D. A. (2004) · Endocrinology · doi:10.1210/en.2004-0392 · Cited by 252 · see citing works
“The high saturation of transferrin, which is the phenotypic hallmark of hemochromatosis, is associated with the presence of nontransferrin-bound iron in plasma, and nontransferrinbound iron is readily taken up by cells via divalent metal transporter-1 (17, 18).”
Association of HFE protein with transferrin receptor in crypt enterocytes of human duodenum
Waheed, A., Parkkila, S., Saarnio, J., Fleming, R. E., Zhou, X. Y., Tomatsu, S., Britton, R. S., Bacon, B. R., & Sly, W. S. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.4.1579 · Cited by 243 · see citing works
Georgatsou, E., & Alexandraki, D. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.5.3065-3073.1994 · Cited by 233 · see citing works
“This activity is proposed to be involved in respiration of some bacterial species (21), in clearance of toxic molecules in higher eukaryotes (14), or in iron uptake in animal cells (37).”
BackgroundCellular and molecular aspects of iron metabolism in plants
Briat, J., Fobis‐Loisy, I., Grignon, N., Lobréaux, S., Pascal, N., Savino, G., Thoiron, S., Nicolaus Von Wirén, A., & Wuytswinkel, O. V. (1995) · Biology of the Cell · doi:10.1016/0248-4900(96)81320-7 · Cited by 227 · see citing works
Role of L-type Ca2+ channels in iron transport and iron-overload cardiomyopathy
Oudit, G. Y., Trivieri, M. G., Khaper, N., Liu, P. P., & Backx, P. H. (2006) · Journal of Molecular Medicine · doi:10.1007/s00109-005-0029-x · Cited by 222 · see citing works
“However, NTBI uptake into excitable cells such as cardiomyocytes, neurons, beta cells of the pancreas and pituitary cells requires reduction of ferric iron (Fe) to ferrous iron (Fe) by a membrane-associated ferri-reductase system, properties that clearly distinguish it from transferrin-receptor-mediated ferric iron up…”
BackgroundThe iron metabolism of neoplastic cells: Alterations that facilitate proliferation?
Kwok, J. C., & Richardson, D. R. (2002) · Critical Reviews in Oncology/Hematology · doi:10.1016/s1040-8428(01)00213-x · Cited by 215 · see citing works
Acute phase proteins and their use in the diagnosis of diseases in ruminants: a review
Tóthová, C., Nagy, O., & Kovác, G. (2014) · Veterinární Medicína · doi:10.17221/7478-vetmed · Cited by 211 · see citing works
“It renders iron soluble under physiological conditions, prevents iron-mediated free radical toxicity, and facilitates transport into cells (Kaplan et al. 1991).”
BackgroundRoy, C. N., Penny, D. M., Feder, J. N., & Enns, C. A. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.13.9022 · Cited by 206 · see citing works
Graham, R. M. (2007) · World Journal of Gastroenterology · doi:10.3748/wjg.v13.i35.4725 · Cited by 180 · 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
Modulation of Iron Uptake in Heart by L-Type Ca2+Channel Modifiers
Tsushima, R. G., Wickenden, A. D., Bouchard, R. A., Oudit, G. Y., Liu, P. P., & Backx, P. H. (1999) · Circulation Research · doi:10.1161/01.res.84.11.1302 · Cited by 157 · see citing works
Waheed, A., Grubb, J. H., Zhou, X., Tomatsu, S., Fleming, R. E., Costaldi, M. E., Britton, R. S., Bacon, B. R., & Sly, W. S. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.042701499 · Cited by 148 · see citing works
Li, X., Chlan‐Fourney, J., Juorio, A. V., Bennett, V. L., Shrikhande, S., Keegan, D. L., Jin, Q., & Boulton, A. A. (1999) · Journal of Neuroscience Research · doi:10.1002/(sici)1097-4547(19990401)56:1 · Cited by 57 · see citing works
Walter, T., Olivares, M., Pizarro, F., & Muñoz, C. (2009) · Nutrition Reviews · doi:10.1111/j.1753-4887.1997.tb06462.x · Cited by 143 · see citing works
Attieh, Z. K., Mukhopadhyay, C. K., Seshadri, V., Tripoulas, N. A., & Fox, P. L. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.2.1116 · Cited by 144 · see citing works
Iron, lipocalin, and kidney epithelia
Yang, J., Mori, K., Li, J. Y., & Barasch, J. M. (2003) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00008.2003 · Cited by 139 · see citing works
Separate pathways for cellular uptake of ferric and ferrous iron
Conrad, M. E., Umbreit, J. N., Moore, E., Hainsworth, L. N., Porubcin, M., Simovich, M. J., Nakada, M. T., Dolan, K. G., & Garrick, M. D. (2000) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.2000.279.4.g767 · Cited by 131 · see citing works
“Tissue culture cells possess a similar capability (15, 27, 36).”
BackgroundTransferrin receptor 1 is differentially required in lymphocyte development
Ned, R. M., Swat, W., & Andrews, N. C. (2003) · Blood · doi:10.1182/blood-2003-04-1086 · Cited by 120 · see citing works
Randell, E. W., Parkes, J. G., Olivieri, N. F., & Templeton, D. M. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)33971-6 · Cited by 127 · see citing works
Molecular biology of iron acquisition in Saccharomyces cerevisiae
Askwith, C. C., de Silva, D., & Kaplan, J. (1996) · Molecular Microbiology · doi:10.1111/j.1365-2958.1996.tb02485.x · Cited by 121 · see citing works
Richardson, D. R., & Baker, E. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)49665-8 · Cited by 118 · 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
Iron homeostasis in breast cancer
Marques, O., da Silva, B. M., Porto, G., & Lopes, C. (2014) · Cancer Letters · doi:10.1016/j.canlet.2014.01.029 · Cited by 115 · see citing works
“such as Fe-citrate and Fenitriacetate [125–130].”
Non protein bound iron as early predictive marker of neonatal brain damage
Buonocore, G., Perrone, S., Longini, M., Paffetti, P., Vezzosi, P., Gatti, M. G., & Bracci, R. (2003) · Brain · doi:10.1093/brain/awg116 · Cited by 110 · see citing works
“When NPBI gains access to the extracellular space, its uptake by cells is enhanced by intracellular calcium and, paradoxically, by increased levels of intracellular iron (Kaplan et al., 1991).”
BackgroundMechanisms of iron uptake by mammalian cells
Qian, Z., & Tang, P. L. (1995) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/0167-4889(95)00098-x · Cited by 107 · see citing works
A novel iron uptake mechanism mediated by GPI‐anchored human p97.
Kennard, M. L., Richardson, D. R., Gabathuler, R., Ponka, P., & Jefferies, W. A. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb00091.x · Cited by 106 · see citing works
A Fluorescence-Based One-Step Assay for Serum Non-Transferrin-Bound Iron
Breuer, W. V., & Cabantchik, Z. I. (2001) · Analytical Biochemistry · doi:10.1006/abio.2001.5378 · Cited by 102 · see citing works
Riedel, H.-D., Remus, A. J., Fitscher, B. A., & Stremmel, W. (1995) · Biochemical Journal · doi:10.1042/bj3090745 · Cited by 90 · see citing works
Jordan, I., & Kaplan, J. (1994) · Biochemical Journal · doi:10.1042/bj3020875 · Cited by 88 · see citing works
DeFelice, L. J., & Goswami, T. (2006) · Annual Review of Physiology · doi:10.1146/annurev.physiol.69.031905.164816 · Cited by 86 · see citing works
“A biological purpose for the G185R gain-of-function mutation may be that elevated intracellular Ca2+ concentrations increase uptake of nontransferrin-bound iron (81, 82).”
BackgroundCentral Nervous System Agents for Ischemic Stroke: Neuroprotection Mechanisms
Pandya, R. S., Mao, L., Zhou, H., Zhou, S., Zeng, J., Popp, A., & Wang, X. (2011) · Central Nervous System Agents in Medicinal Chemistry · doi:10.2174/187152411796011321 · Cited by 84 · see citing works
“Free iron crosses the damaged blood-brain barrier (BBB) and is taken up by cells in a transferrinindependent manner [25].”
BackgroundIron Transport Across Biologic Membranes
Andrews, N. C., Fleming, M. D., & Gunshin, H. (2009) · Nutrition Reviews · doi:10.1111/j.1753-4887.1999.tb06934.x · Cited by 84 · see citing works
Knisely, A. S. (1992) · Advances in Pediatrics · doi:10.1016/s0065-3101(24)00290-1 · Cited by 84 · see citing works
The mechanism of 67Ga localization in malignant disease
Weiner, R. E. (1996) · Nuclear Medicine and Biology · doi:10.1016/0969-8051(96)00119-9 · Cited by 83 · see citing works
Wessling‐Resnick, M. (2000) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.20.1.129 · Cited by 81 · see citing works
Tissue Iron Overload and Mechanisms of Iron-Catalyzed Oxidative Injury
Lesnefsky, E. J. (1994) · Advances in experimental medicine and biology · doi:10.1007/978-1-4615-1833-4_10 · Cited by 79 · see citing works
Corsi, B., Levi, S., Cozzi, A., Corti, A., Altimare, D., Albertini, A., & Arosio, P. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)01330-7 · Cited by 73 · see citing works
Inman, R. S., Coughlan, M. M., & Wessling-Resnick, M. (1994) · Biochemistry · doi:10.1021/bi00205a022 · Cited by 70 · see citing works
A Spontaneous, Recurrent Mutation in Divalent Metal Transporter-1 Exposes a Calcium Entry Pathway
Xu, H., Jin, J., DeFelice, L. J., Andrews, N. C., & Clapham, D. E. (2004) · PLoS Biology · doi:10.1371/journal.pbio.0020050 · Cited by 72 · see citing works
“iron uptake through an undefined transport system that has characteristics distinct from DMT1 (Kaplan et al. 1991).”
BackgroundRichardson, D. R. (2000) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.2000.01079.x · Cited by 72 · see citing works
Characterisation of non-transferrin-bound iron (ferric citrate) uptake by rat hepatocytes in culture
Baker, E., Baker, S. M., & Morgan, E. H. (1998) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/s0304-4165(97)00120-7 · Cited by 72 · see citing works
Wessling‐Resnick, M. (1999) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409239991209318 · Cited by 72 · see citing works
Zinc Inhibition of cAMP Signaling
Klein, C., Sunahara, R. K., Hudson, T. Y., Heyduk, T., & Howlett, A. C. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m108808200 · Cited by 70 · see citing works
The PICALM Protein Plays a Key Role in Iron Homeostasis and Cell Proliferation
Scotland, P., Heath, J. L., Conway, A. E., Porter, N. B., Armstrong, M. B., Walker, J. A., Klebig, M. L., Lavau, C., & Wechsler, D. S. (2012) · PLoS ONE · doi:10.1371/journal.pone.0044252 · Cited by 67 · see citing works
“FAC is a low-molecular-weight form of iron that can penetrate into cells by bypassing the transferrin endocytic pathway [36].”
BackgroundRole of labile iron in the toxicity of pharmacological ascorbate
Du, J., Wagner, B. A., Buettner, G. R., & Cullen, J. J. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.03.033 · Cited by 67 · see citing works
Bartfay, W. J., & Bartfay, E. (2000) · Biological Research For Nursing · doi:10.1177/109980040000200106 · Cited by 66 · see citing works
Intracellular Labile Iron Modulates Adhesion of Human Monocytes to Human Endothelial Cells
Kartikasari, A. E. R., Georgiou, N., Visseren, F. L. J., Kats-Renaud, H. J. V., van Asbeck, B. S., & Marx, J. J. M. (2004) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000147406.00871.b3 · Cited by 66 · see citing works
Olakanmi, O., McGowan, S. E., Hayek, M. B., & Britigan, B. E. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116310 · Cited by 66 · see citing works
Wingert, R. A., Brownlie, A., Galloway, J. L., Dooley, K. A., Fraenkel, P. G., Axe, J. L., Davidson, A. J., Barut, B., Noriega, L., Sheng, X., et al. (2004) · Development · doi:10.1242/dev.01540 · Cited by 65 · see citing works
“…include direct uptake of non-Tf-bound iron (NTBI) (Baker et al., 1998; Goto et al., 1983; Hodgson et al., 1995; Inman and WesslingResnick, 1993; Kaplan et al., 1991; Sturrock et al., 1990), Tfr1-independent uptake of Tf-bound iron (Chan et al., 1992; Thorstensen et al., 1995), and…”
BackgroundCOMPARATIVE NUTRITIONOF IRON AND COPPER
Winzerling, J. J., & Law, A. J. H. (1997) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.17.1.501 · Cited by 65 · see citing works
Oshiro, S., Kawahara, M., Kuroda, Y., Zhang, C., Cai, Y., Kitajima, S., & Shirao, M. (2000) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/s0925-4439(00)00065-x · Cited by 64 · see citing works
Tinoco, A. D., Saxena, M., Sharma, S., Noinaj, N., Delgado, Y., González, E. P. Q., Conklin, S. E., Zambrana, N., Loza-Rosas, S. A., & Parks, T. B. (2016) · Journal of the American Chemical Society · doi:10.1021/jacs.6b01966 · Cited by 65 · see citing works
Iron uptake and Nramp2/DMT1/DCT1 in human bronchial epithelial cells
Wang, X., Ghio, A. J., Yang, F., Dolan, K. G., Garrick, M. D., & Piantadosi, C. A. (2002) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00253.2001 · Cited by 74 · see citing works
“Pretreatment of BEAS-2B cells with iron-containing compounds increased NTBI transport, whereas chelator pretreatment had no effect.”
BackgroundInfluentialRole of ceruloplasmin and ascorbate in cellular iron release
Richardson, D. R. (1999) · Journal of Laboratory and Clinical Medicine · doi:10.1016/s0022-2143(99)90166-x · Cited by 61 · see citing works
Neuroprotection by tempol in a model of iron-induced oxidative stress in acute ischemic stroke
Mehta, S. H., Webb, R. C., Ergul, A., Tawak, A., & Dorrance, A. M. (2004) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00446.2002 · Cited by 59 · see citing works
“However, in case of stroke, free plasma iron could leak across the damaged BBB, and this iron would be taken up by cells in a Tf-independent manner (14).”
BackgroundInfluentialParkes, J. G., Randell, E. W., Olivieri, N. F., & Templeton, D. M. (1995) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/0304-4165(94)00162-q · Cited by 58 · see citing works
Lane, D. J. R., & Lawen, A. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m800713200 · Cited by 56 · see citing works
Lee, D.-H., & Jacobs, D. R. (2004) · Medical Hypotheses · doi:10.1016/s0306-9877(03)00344-x · Cited by 54 · see citing works
Hémadi, M., Miquel, G., Kahn, P. H., & El Hage Chahine, J.-M. (2003) · Biochemistry · doi:10.1021/bi020627p · Cited by 60 · see citing works
Correnti, C., Richardson, V., Sia, A. K., Bandaranayake, A. D., Ruiz, M., Rahmanto, Y. S., Kovačević, Ž., Clifton, M. C., Holmes, M. A., Kaiser, B. K., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0043696 · Cited by 52 · see citing works
“The greater uptake of (59)Fe from (59)FeCl3 than (59)FeEnt by cells can be attributed to the presence of specific transporters on HeLa cells that are known to transport low Mr iron [21,22].”
BackgroundAlternate iron transport pathway. Mobilferrin and integrin in K562 cells.
Conrad, M. E., Umbreit, J. N., Moore, E., Uzel, C., & Berry, M. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)37263-0 · Cited by 53 · see citing works
Saxena, M., Loza-Rosas, S. A., Gaur, K., Sharma, S., Otero, S. C. P., & Tinoco, A. D. (2018) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2018.03.006 · Cited by 51 · see citing works
Regulatory effects of gallium on transferrin-independent iron uptake by human leukemic HL60 cells
Chitambar, C., & Sax, D. (1992) · Blood · doi:10.1182/blood.v80.2.505.505 · Cited by 51 · see citing works
Richardson, D. R., & Ponka, P. (1995) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/0167-4889(95)00096-b · Cited by 50 · see citing works
Iliev, P. T., & Georgieva, T. M. (2018) · BULGARIAN JOURNAL OF VETERINARY MEDICINE · doi:10.15547/bjvm.1050 · Cited by 49 · see citing works
“According to Broch et al. (1987), Kaplan et al. (1991) and Gkouvatsos et al. (2012), iron chelation by transferrin has some important functions such as maintaining Fe3+ in soluble form under physiological conditions; supporting iron transport and cellular uptake; maintaining Fe3+ in a redox-inert…”
BackgroundTang, S. C. W., Lai, K. N., Chan, T. M., Lan, H. Y., Ho, S. K., & Sacks, S. H. (2001) · American Journal of Kidney Diseases · doi:10.1053/ajkd.2001.20593 · Cited by 49 · see citing works
Olakanmi, O., Schlesinger, L., Ahmed, A., & Britigan, B. (2004) · Infection and Immunity · doi:10.1128/iai.72.4.2022-2028.2004 · Cited by 48 · see citing works
Iron crosses the endosomal membrane by a carrier-mediated process
Qian, Z. M., Tang, P. L., & Wang, Q. L. (1997) · Progress in Biophysics and Molecular Biology · doi:10.1016/s0079-6107(97)00009-6 · Cited by 49 · see citing works
Transferrin-independent iron uptake supports B lymphocyte growth
Seligman, P. A., Kovar, J., Schleicher, R. B., & Gelfand, E. W. (1991) · Blood · doi:10.1182/blood.v78.6.1526.1526 · Cited by 48 · see citing works
Oxidative injury in neonatal erythrocytes
Perrone, S., Tataranno, M. L., Stazzoni, G., Vecchio, A. D., & Buonocore, G. (2012) · The Journal of Maternal-Fetal & Neonatal Medicine · doi:10.3109/14767058.2012.715471 · Cited by 47 · see citing works
“extracellular space, its uptake by cells is enhanced by intracellular calcium and paradoxically also by increased levels of intracellular iron [49].”
BackgroundCardiac function and cytotoxic aldehyde production in a murine model of chronic iron-overload
Bartfay, W. J. (1999) · Cardiovascular Research · doi:10.1016/s0008-6363(99)00040-1 · Cited by 47 · see citing works
Sorond, F. A., & Ratan, R. R. (2000) · Antioxidants and Redox Signaling · doi:10.1089/15230860050192206 · Cited by 46 · see citing works
“In this scenario, iron would be directly taken up by cells in a manner that is independent of Tf, and the “free” iron would be quite redox active (Kaplan et al. , 1991).”
Role of the clathrin adaptor PICALM in normal hematopoiesis and polycythemia vera pathophysiology
Ishikawa, Y., Maeda, M., Pasham, M. R., Aguet, F., Tacheva-Grigorova, S. K., Masuda, T., Yi, H. F., Lee, S.-U., Xu, J., Teruya‐Feldstein, J., et al. (2014) · Haematologica · doi:10.3324/haematol.2014.119537 · Cited by 44 · see citing works
“Ferric ammonium citrate incorporates into cells through “TfR-independent” mechanisms.(24) Importantly, treatment with ferric ammonium citrate dose-dependently restored development of Picalmdeficient mature erythroblasts (Figure 6G), indicating that lack of TfR-mediated iron uptake is the primary cause of erythroid def…”
Oshiro, S., Kawamura, K., Zhang, C., Sone, T., Morioka, M. S., Kobayashi, S., & Nakajima, K. (2008) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2007.12.002 · Cited by 43 · see citing works
Lane, D. J. R., Bae, D.-H., Siafakas, A. R., Rahmanto, Y. S., Al-Akra, L., Jansson, P. J., Casero, R. A., & Richardson, D. R. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2018.05.007 · Cited by 41 · see citing works
“Cells were incubated with control medium, or this medium containing the well-characterized iron chelators, 311 (25 μM), or DFO (100 μM) [15, 16, 29, 40], or the cellular iron donor, FAC (100 μg/mL) [46, 56, 57]), for 24 or 48 h/37°C (Figs.”
BackgroundDifferential accumulation of non-transferrin-bound iron by cardiac myocytes and fibroblasts
Liu, Y. (2003) · Journal of Molecular and Cellular Cardiology · doi:10.1016/s0022-2828(03)00072-5 · Cited by 42 · see citing works
Characterization of Fe2+ and Fe3+ transport by iron-loaded cardiac myocytes
Parkes, J. G. (1997) · Toxicology · doi:10.1016/s0300-483x(96)03566-4 · Cited by 42 · see citing works
Regulation of Oxidant Production in Acute Lung Injury
Sanders, K. A., Huecksteadt, T. P., Xu, P., Sturrock, A., & Hoidal, J. R. (1999) · CHEST Journal · doi:10.1378/chest.116.suppl_1.56s · Cited by 41 · see citing works
Oshiro, S., Kawahara, M., Mika, S. S., Muramoto, K., Kobayashi, K., Ishige, R., Nozawa, K., Hori, M., Yung, C., Kitajima, S., et al. (1998) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a021914 · Cited by 41 · see citing works
“is observed in human skin fibroblasts (3).”
BackgroundOshiro, S., Nakajima, H., Markello, T. C., Krasnewich, D. M., Bernardini, I. M., & Gahl, W. A. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)80581-x · Cited by 41 · see citing works
Sánchez‐López, R., & Haldar, K. (1992) · Molecular and Biochemical Parasitology · doi:10.1016/0166-6851(92)90122-z · Cited by 40 · see citing works
Intracellular and Extracellular Labile Iron Pools
Cabantchik, Z. I., Kakhlon, O., Epsztejn, S., Zanninelli, G., & Breuer, W. V. (2002) · Advances in experimental medicine and biology · doi:10.1007/978-1-4615-0593-8_4 · Cited by 39 · see citing works
Influence of Copper Depletion on Iron Uptake Mediated by SFT, a Stimulator of Fe Transport
Yu, J., & Wessling‐Resnick, M. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.12.6909 · Cited by 38 · see citing works
Transferrin receptor expression in myelin deficient (md)rats
Roskams, A. J., & Connor, J. R. (1992) · Journal of Neuroscience Research · doi:10.1002/jnr.490310304 · Cited by 39 · see citing works
Chaudhary, A., & Poonia, K. (2021) · Inorganic Chemistry Communications · doi:10.1016/j.inoche.2021.109044 · Cited by 39 · see citing works
The role of iron and iron binding proteins in lymphocyte physiology and pathology
Kemp, J. D. (1993) · Journal of Clinical Immunology · doi:10.1007/bf00919264 · Cited by 37 · see citing works
Ghio, A. J., Soukup, J. M., Dailey, L. A., & Madden, M. C. (2020) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2020.02.007 · Cited by 39 · see citing works
Characterisation of citrate and iron citrate uptake by cultured rat hepatocytes
Graham, R. M., Morgan, E. H., & Baker, E. (1998) · Journal of Hepatology · doi:10.1016/s0168-8278(98)80156-6 · Cited by 36 · see citing works
Aluminum exposure affects transferrin-dependent and -independent iron uptake by K562 cells
Pérez, G., Pregi, N., Vittori, D. C., Risio, C. D., Garbossa, G., & Nesse, A. B. (2005) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2004.12.002 · Cited by 35 · see citing works
“The mechanisms that can be proposed to explain NTBI uptake modulation in response to Al exposure may involve the appearance of previously cryptic carriers [10] or the increase in the synthesis of transport proteins since Al proved to be able to translocate into the nucleus and interact with genetic material [29,30].”
BackgroundEtiologies, Consequences, and Treatment of Iron Overload
Gordeuk, V. R., McLaren, G. D., Samowitz, W. S., & Rouault, T. A. (1994) · Critical Reviews in Clinical Laboratory Sciences · doi:10.3109/10408369409084674 · Cited by 35 · see citing works
Brown, J. X., Buckett, P. D., & Wessling‐Resnick, M. (2004) · Chemistry & Biology · doi:10.1016/j.chembiol.2004.02.016 · Cited by 33 · see citing works
New Perspectives on Iron Uptake in Eukaryotes
Sherman, H. G., Jovanovic, C., Stolnik, S., Baronian, K. H. R., Downard, A. J., & Rawson, F. J. (2018) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2018.00097 · Cited by 31 · see citing works
“It was stated that to deal with increases in extracellular iron, this upregulation of non-transferrin transport was required (Kaplan et al., 1991).”
BackgroundMRI Susceptibility Changes Suggestive of Iron Deposition in the Thalamus after Ischemic Stroke
van Etten, E. S., van der Grond, J., Dumas, E. M., van den Bogaard, S. J. A., van Buchem, M. A., & Wermer, M. J. H. (2015) · Cerebrovascular Diseases · doi:10.1159/000433560 · Cited by 32 · see citing works
- Authors
- Kaplan, J., Jordan, I., & Sturrock, A.
- Affiliations
- University of Utah (US)
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1991-02
- Volume
- 266
- Issue
- 5
- Pages
- 2997-3004
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1587837383
- Cited by
- 198
- References
- 26
- Citations by year
- 2026: 2 · 2024: 1 · 2023: 1 · 2021: 1 · 2020: 2 · 2019: 2 · 2018: 8 · 2016: 3 · 2015: 3 · 2014: 4 · 2013: 8 · 2012: 5
- FWCI
- 6.12
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01dk020630-22)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK20630, DK30534)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Micronutrient Interactions and Effects
- Keywords
- iron uptake regulation, transferrin receptor, extracellular iron, copper, zinc, intracellular calcium, iron accumulation, cultured cells
- MeSH terms
- Biological Transport, Cadmium, Calcium, Copper, Cycloheximide, Ferritins, HeLa Cells, Humans, Iron, Manganese, Transferrin, Zinc
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
