Targeted gene disruption reveals an essential role for ceruloplasmin in cellular iron efflux
Open accessAbstract
Aceruloplasminemia is an autosomal recessive disorder of iron metabolism. Affected individuals evidence iron accumulation in tissue parenchyma in association with absent serum ceruloplasmin. Genetic studies of such patients reveal inherited mutations in the ceruloplasmin gene. To elucidate the role of ceruloplasmin in iron homeostasis, we created an animal model of aceruloplasminemia by disrupting the murine ceruloplasmin ( Cp ) gene. Although normal at birth, Cp −/− mice demonstrate progressive accumulation of iron such that by one year of age all animals have a prominent elevation in serum ferritin and a 3- to 6-fold increase in the iron content of the liver and spleen. Histological analysis of affected tissues in these mice shows abundant iron stores within reticuloendothelial cells and hepatocytes. Ferrokinetic studies in Cp +/+ and Cp −/− mice reveal equivalent rates of iron absorption and plasma iron turnover, suggesting that iron accumulation results from altered compartmentalization within the iron cycle. Consistent with this concept, Cp −/− mice showed no abnormalities in cellular iron uptake but a striking impairment in the movement of iron out of reticuloendothelial cells and hepatocytes. Our findings reveal an essential physiologic role for ceruloplasmin in determining the rate of iron efflux from cells with mobilizable iron stores.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Coexposure to iron and H2O2 enhances α-synuclein aggregation in vitro.
“Coexposure to iron and H2O2 were shown to enhance α-synuclein aggregation in vitro (126).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [126]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Cloning and characterization of a mammalian proton-coupled metal-ion transporter
Gunshin, H., Mackenzie, B., Berger, U. V., Gunshin, Y., Romero, M. F., Boron, W. F., Nussberger, S., Gollan, J. L., & Hediger, M. A. (1997) · Nature · doi:10.1038/41343 · Cited by 3,166 · see citing works
Neonatal lethality and lymphopenia in mice with a homozygous disruption of the c-abl proto-oncogene
Tybulewicz, V. L. J., Crawford, C. E., Jackson, P. K., Bronson, R. T., & Mulligan, R. C. (1991) · Cell · doi:10.1016/0092-8674(91)90011-m · Cited by 1,281 · see citing works
Microcytic anaemia mice have a mutation in Nramp2, a candidate iron transporter gene
Fleming, M. D., Trenor, C. C., Su, M. A., Foernzler, D., Beier, D. R., Dietrich, W. F., & Andrews, N. C. (1997) · Nature Genetics · doi:10.1038/ng0897-383 · Cited by 1,159 · see citing works
Vulpe, C. D., Kuo, Y.-M., Murphy, T. L., Cowley, L., Askwith, C., Libina, N., Gitschier, J., & Anderson, G. J. (1999) · Nature Genetics · doi:10.1038/5979 · Cited by 1,084 · see citing works
Heme oxygenase 1 is required for mammalian iron reutilization
Poss, K. D., & Tonegawa, S. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.20.10919 · Cited by 1,016 · see citing works
Regulation of Mitochondrial Iron Accumulation by Yfh1p, a Putative Homolog of Frataxin
Babcock, M., de Silva, D., Oaks, R., Davis-Kaplan, S., Jiralerspong, S., Montermini, L., Pandolfo, M., & Kaplan, J. (1997) · Science · doi:10.1126/science.276.5319.1709 · Cited by 921 · see citing works
The possible significance of the ferrous oxidase activity of ceruloplasmin in normal human serum.
Osaki, S., Johnson, D. A., & Frieden, E. (1966) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)96527-0 · Cited by 679 · see citing works
Transferrin receptor is necessary for development of erythrocytes and the nervous system
Levy, J. E., Jin, O., Fujiwara, Y., Kuo, F., & Andrews, N. (1999) · Nature Genetics · doi:10.1038/7727 · Cited by 574 · see citing works
Aceruloplasminemia: molecular characterization of this disorder of iron metabolism.
Harris, Z. L., Takahashi, Y., Miyajima, H., Serizawa, M., MacGillivray, R. T., & Gitlin, J. D. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.7.2539 · Cited by 558 · see citing works
Self-citationFunction and regulation of transferrin and ferritin.
Ponka, P., Beaumont, C., & Richardson, D. R. (1998) · PubMed · Cited by 524 · see citing works
HFE gene knockout produces mouse model of hereditary hemochromatosis
Zhou, X. Y., Tomatsu, S., Fleming, R. E., Parkkila, S., Waheed, A., Jiang, J., Fei, Y., Brunt, E. M., Ruddy, D. A., Prass, C. E., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.5.2492 · Cited by 519 · see citing works
A mutation in the ceruloplasmin gene is associated with systemic hemosiderosis in humans
Yoshida, K., Furihata, K., Takeda, S., Nakamura, A., Yamamoto, K., Morita, H., Hiyamuta, S., Ikeda, S.-I., Shimizu, N., & Yanagisawa, N. (1995) · Nature Genetics · doi:10.1038/ng0395-267 · Cited by 463 · see citing works
Iron metabolism in health and disease
Baldus, W. P. (1995) · Gastroenterology · doi:10.1016/0016-5085(95)90247-3 · Cited by 380 · see citing works
The role of ceruloplasmin in iron metabolism.
Roeser, H. P., Lee, G. R., Nacht, S., & Cartwright, G. E. (1970) · Journal of Clinical Investigation · doi:10.1172/jci106460 · Cited by 365 · see citing works
The X-ray structure of human serum ceruloplasmin at 3.1 Å: nature of the copper centres
Zaitseva, I., Zaitsev, V., Card, G. L., Ka, M., Bax, B. D., Ralph, A. C., & Lindley, P. F. (1996) · JBIC Journal of Biological Inorganic Chemistry · doi:10.1007/s007750050018 · Cited by 355 · see citing works
Patel, B. N., & David, S. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.32.20185 · Cited by 327 · see citing works
Familial apoceruloplasmin deficiency associated with blepharospasm and retinal degeneration
Miyajima, H., Nishimura, Y., Mimguchi, K., Sakamoto, M., Shimizu, T., & Honda, N. (1987) · Neurology · doi:10.1212/wnl.37.5.761 · Cited by 295 · see citing works
The Yeast Frataxin Homologue Mediates Mitochondrial Iron Efflux
Radisky, D. C., Babcock, M. C., & Kaplan, J. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.8.4497 · Cited by 277 · see citing works
Fleming, R. E., Migas, M. C., Zhou, X., Jiang, J., Britton, R. S., Brunt, E. M., Tomatsu, S., Waheed, A., Bacon, B. R., & Sly, W. S. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.6.3143 · Cited by 269 · 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
Iron metabolism in copper-deficient swine
Lee, G. R., Nacht, S., Lukens, J. N., & Cartwright, G. E. (1968) · Journal of Clinical Investigation · doi:10.1172/jci105891 · Cited by 259 · see citing works
Aceruloplasminemia: an inherited neurodegenerative disease with impairment of iron homeostasis
Harris, Z. L., Klomp, L. W. J., & Gitlin, J. (1998) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/67.5.972s · Cited by 253 · see citing works
Self-citationMorita, H., Ikeda, S., Yamamoto, K., Morita, S., Yoshida, K., Nomoto, S., Kato, M., & Yanagisawa, N. (1995) · Annals of Neurology · doi:10.1002/ana.410370515 · Cited by 245 · see citing works
Regulation of Iron Metabolism in Eukaryotes
Rouault, T. A., & Klausner, R. D. (1997) · Current topics in cellular regulation · doi:10.1016/s0070-2137(97)80001-5 · Cited by 239 · see citing works
The Mobilization of Iron from the Perfused Mammalian Liver by a Serum Copper Enzyme, Ferroxidase I
Osaki, S., Johnson, D. A., & Frieden, E. (1971) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)62284-7 · Cited by 236 · see citing works
Crystal, R. G. (1997) · Nature Medicine · doi:10.1038/nm0497-383 · Cited by 204 · see citing works
Role of Ceruloplasmin in Cellular Iron Uptake
Mukhopadhyay, C. K., Attieh, Z. K., & Fox, P. L. (1998) · Science · doi:10.1126/science.279.5351.714 · Cited by 199 · see citing works
Ceruloplasmin gene expression in the murine central nervous system.
Klomp, L. W. J., Farhangrazi, Z. S., Dugan, L. L., & Gitlin, J. D. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118768 · Cited by 194 · see citing works
Self-citationFillet, G., Beguin, Y., & Baldelli, L. (1989) · Blood · doi:10.1182/blood.v74.2.844.844 · Cited by 146 · see citing works
Regulation of Transition Metal Transport across the Yeast Plasma Membrane
Radisky, D. C., & Kaplan, J. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.8.4481 · Cited by 145 · 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
Gitlin, J. D. (1998) · Pediatric Research · doi:10.1203/00006450-199809000-00001 · Cited by 140 · see citing works
Self-citationHereditary caeruloplasmin deficiency, dementia and diabetes mellitus
LOGAN, J. I., HARVEYSON, K. B., WISDOM, G. B., HUGHES, A. E., & ARCHBOLD, G. P. R. (1994) · QJM · doi:10.1093/oxfordjournals.qjmed.a068881 · Cited by 130 · see citing works
Iron Metabolism in Eukaryotes—Mars and Venus at It Again
Kaplan, J., & O’Halloran, T. V. (1996) · Science · doi:10.1126/science.271.5255.1510 · Cited by 124 · see citing works
Using Embryonic Stem Cells to Introduce Mutations into the Mouse Germ Line1
Robertson, E. J. (1991) · Biology of Reproduction · doi:10.1095/biolreprod44.2.238 · Cited by 122 · see citing works
Storage Iron Kinetics. VII. A BIOLOGIC MODEL FOR RETICULOENDOTHELIAL IRON TRANSPORT
Fillet, G., Cook, J. D., & Finch, C. A. (1974) · Journal of Clinical Investigation · doi:10.1172/jci107703 · Cited by 113 · see citing works
Iron Is Hot: An Update on the Pathophysiology of Hemochromatosis
Andrews, N. C., & Levy, J. E. (1998) · Blood · doi:10.1182/blood.v92.6.1845.418k35_1845_1851 · Cited by 85 · see citing works
Yu, J., Yu, Z. K., & Wessling‐Resnick, M. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.52.34675 · Cited by 24 · see citing works
New knowledge of genetic pathogenesis of hemochromatosis and Wilson's disease.
Bacon, B. R., & Schilsky, M. L. (1999) · PubMed · Cited by 21 · see citing works
Expression of autoimmune disease-related antigens by cells of the immune system
Mor, F., Boccaccio, G. L., & Unger, T. (1998) · Journal of Neuroscience Research · doi:10.1002/(sici)1097-4547(19981015)54:2 · Cited by 19 · see citing works
Flagged first, then by citations
Research works printed but not linked: 9
- [1]Ponka P, Beaumont C, Richardson D R. Semin Hematol. 1998;35:35–54. [PubMed] [Google Scholar]
- [3]Andrews N C, Levy J E. Blood. 1998;92:1845–1851. [PubMed] [Google Scholar]
- [4]Bacon B R, Schilsky M L. Adv Intern Med. 1999;44:91–116. [PubMed] [Google Scholar]
- [7]Logan J I, Harveyson K B, Wisdom G B, Hughes A E, Archbold G P R. Q J Med. 1994;87:663–670. [PubMed] [Google Scholar]
- [13]Osaki S, Johnson D A, Freiden E. J Biol Chem. 1971;246:3018–3023. [PubMed] [Google Scholar]
- [20]Osaki S, Johnson D A, Frieden E. J Biol Chem. 1966;241:2746–2751. [PubMed] [Google Scholar]
- [21]Torrance J D, Bothwell T H. In: Methods in Hematology: Iron. Cook J D, editor. New York: Churchill Livingstone; 1980. pp. 104–109. [Google Scholar]
- [24]Fillet G, Beguin Y, Baldelli L. Blood. 1989;74:844–851. [PubMed] [Google Scholar]
- [25]Zaitseva I, Zaitsev V, Cara G, Mojhkov K, Bar B, Lindley P F. J Biol Inorg Chem. 1996;1:15–23. [Google Scholar]
Cited by
Sorted by citations
Iron, brain ageing and neurodegenerative disorders
Zecca, L., Youdim, M. B. H., Riederer, P., Connor, J. R., & Crichton, R. R. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1537 · Cited by 1,801 · see citing works
Hentze, M. W., Muckenthaler, M. U., & Andrews, N. C. (2004) · Cell · doi:10.1016/s0092-8674(04)00343-5 · Cited by 1,736 · see citing works
Mechanisms for copper acquisition, distribution and regulation
Kim, B., Nevitt, T., & Thiele, D. J. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.72 · Cited by 1,598 · see citing works
Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation
Ganz, T. (2003) · Blood · doi:10.1182/blood-2003-03-0672 · Cited by 1,544 · see citing works
Nicolas, G., Bennoun, M., Devaux, I., Beaumont, C., Grandchamp, B., Kahn, A., & Vaulont, S. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.151179498 · Cited by 1,233 · see citing works
Ganz, T. (2013) · Physiological Reviews · doi:10.1152/physrev.00008.2013 · Cited by 1,122 · see citing works
Trace elements in human physiology and pathology. Copper
Tapiero, H., Townsend, D. M., & Tew, K. D. (2003) · Biomedicine & Pharmacotherapy · doi:10.1016/s0753-3322(03)00012-x · Cited by 1,030 · see citing works
C ERULOPLASMIN M ETABOLISM AND F UNCTION
Hellman, N. E., & Gitlin, J. D. (2002) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.22.012502.114457 · Cited by 930 · see citing works
Self-citationThe roles of iron in health and disease
Lieu, P. T., Heiskala, M. K., Peterson, P. A., & Yang, Y. M. (2001) · Molecular Aspects of Medicine · doi:10.1016/s0098-2997(00)00006-6 · Cited by 813 · see citing works
Chemistry and biology of eukaryotic iron metabolism
Aisen, P. (2001) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/s1357-2725(01)00063-2 · Cited by 804 · see citing works
Muckenthaler, M. U., Galy, B., & Hentze, M. W. (2008) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.28.061807.155521 · Cited by 701 · see citing works
Andrews, N. C., & Schmidt, P. J. (2006) · Annual Review of Physiology · doi:10.1146/annurev.physiol.69.031905.164337 · Cited by 640 · see citing works
Drakesmith, H., Nemeth, E., & Ganz, T. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.09.006 · Cited by 638 · see citing works
Copper and iron disorders of the brain
Madsen, E., & Gitlin, J. D. (2007) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.30.051606.094232 · Cited by 557 · see citing works
Self-citationIntracellular iron transport and storage: from molecular mechanisms to health implications
Mackenzie, E. L., Iwasaki, K., & Tsuji, Y. (2008) · Antioxidants & Redox Signaling · doi:10.1089/ars.2007.1893 · Cited by 526 · see citing works
Taylor, A. A., Tsuji, J. S., Garry, M. R., McArdle, M. E., Goodfellow, W. L., Adams, W. J., & Menzie, C. A. (2019) · Environmental Management · doi:10.1007/s00267-019-01234-y · Cited by 518 · see citing works
The molecular mechanisms of copper metabolism and its roles in human diseases
Chen, J., Jiang, Y., Shi, H., Peng, Y., Fan, X., & Li, C. (2020) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-020-02412-2 · Cited by 488 · see citing works
Essential role for mammalian copper transporter Ctr1 in copper homeostasis and embryonic development
Lee, J., Prohaska, J. R., & Thiele, D. J. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.111058698 · Cited by 467 · see citing works
Kozłowski, H., Janicka-Kłos, A., Brasuń, J., Gaggelli, E., Valensin, D., & Valensin, G. (2009) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2009.05.011 · Cited by 467 · see citing works
Regulation of iron acquisition and storage: consequences for iron-linked disorders
De Domenico, I., McVey Ward, D., & Kaplan, J. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2295 · Cited by 464 · see citing works
Overview of iron metabolism in health and disease
Dev, S., & Babitt, J. L. (2017) · Hemodialysis International · doi:10.1111/hdi.12542 · Cited by 469 · see citing works
Brissot, P., Pietrangelo, A., Adams, P. C., de Graaff, B., McLaren, C. E., & Loréal, O. (2018) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2018.16 · Cited by 430 · see citing works
Iron homeostasis: insights from genetics and animal models
Andrews, N. C. (2000) · Nature Reviews Genetics · doi:10.1038/35042073 · Cited by 418 · see citing works
Mechanistic and regulatory aspects of intestinal iron absorption
Gulec, S., Anderson, G. J., & Collins, J. F. (2014) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00348.2013 · Cited by 406 · see citing works
Animal models of age related macular degeneration
Pennesi, M. E., Neuringer, M., & Courtney, R. J. (2012) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2012.06.003 · Cited by 391 · see citing works
Iron homeostasis during pregnancy
Fisher, A. L., & Nemeth, E. (2017) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.117.155812 · Cited by 409 · see citing works
Ceruloplasmin regulates iron levels in the CNS and prevents free radical injury
Patel, B. N., Dunn, R. J., Jeong, S. Y., Zhu, Q., Julien, J.-P., & David, S. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-15-06578.2002 · Cited by 379 · see citing works
Jeong, S. Y., & David, S. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m301988200 · Cited by 377 · see citing works
Iron Toxicity in Diseases of Aging: Alzheimer's Disease, Parkinson's Disease and Atherosclerosis
Altamura, S., & Muckenthaler, M. U. (2009) · Journal of Alzheimer's Disease · doi:10.3233/jad-2009-1010 · Cited by 369 · see citing works
Liver iron sensing and body iron homeostasis
Wang, C.-Y., & Babitt, J. L. (2019) · Blood · doi:10.1182/blood-2018-06-815894 · Cited by 360 · see citing works
Brain iron pathways and their relevance to Parkinson's disease
Berg, D., Gerlach, M., Youdim, M. B. H., Double, K. L., Zecca, L., Riederer, P., & Becker, G. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00608.x · Cited by 362 · see citing works
Metabolic crossroads of iron and copper
Collins, J. F., Prohaska, J. R., & Knutson, M. D. (2010) · Nutrition Reviews · doi:10.1111/j.1753-4887.2010.00271.x · Cited by 352 · see citing works
Iron Metabolism in the Reticuloendothelial System
Knutson, M. D., & Wessling‐Resnick, M. (2003) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/713609210 · Cited by 349 · see citing works
Molecular control of iron transport
Ganz, T. (2007) · Journal of the American Society of Nephrology · doi:10.1681/asn.2006070802 · Cited by 353 · see citing works
Hepcidin, A New Iron Regulatory Peptide
Nicolas, G., Viatte, L., Bennoun, M., Beaumont, C., Kahn, A., & Vaulont, S. (2002) · Blood Cells Molecules and Diseases · doi:10.1006/bcmd.2002.0573 · Cited by 348 · see citing works
Martin, F., Linden, T., Katschinski, D. M., Oehme, F., Flamme, I., Mukhopadhyay, C. K., Eckhardt, K., Tröger, J., Barth, S., Camenisch, G., et al. (2005) · Blood · doi:10.1182/blood-2004-10-3980 · Cited by 340 · see citing works
Iron misregulation in the brain: a primary cause of neurodegenerative disorders
Ke, Y., & Qian, Z. (2003) · The Lancet Neurology · doi:10.1016/s1474-4422(03)00353-3 · Cited by 339 · see citing works
High‐field magnetic resonance imaging of brain iron: birth of a biomarker?
Schenck, J. F., & Zimmerman, E. A. (2004) · NMR in Biomedicine · doi:10.1002/nbm.922 · Cited by 330 · 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
Mechanisms of Brain Iron Transport: Insight into Neurodegeneration and CNS Disorders
Mills, E., Dong, X.-P., Wang, F., & Xu, H. (2010) · Future Medicinal Chemistry · doi:10.4155/fmc.09.140 · Cited by 309 · see citing works
Ceruloplasmin and other copper binding components of blood plasma and their functions: an update
Linder, M. C. (2016) · Metallomics · doi:10.1039/c6mt00103c · Cited by 308 · see citing works
Iron in Chronic Brain Disorders: Imaging and Neurotherapeutic Implications
Stankiewicz, J. M., Panter, S. S., Neema, M., Arora, A., Batt, C. E., & Bakshi, R. (2007) · Neurotherapeutics · doi:10.1016/j.nurt.2007.05.006 · Cited by 301 · see citing works
An overview of molecular basis of iron metabolism regulation and the associated pathologies
Silva, B., & Faustino, P. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.03.011 · Cited by 300 · see citing works
Brain iron uptake and homeostatic mechanisms: An overview
Burdo, J. R., & Connor, J. R. (2003) · BioMetals · doi:10.1023/a:1020718718550 · Cited by 292 · see citing works
Puig, S., Andrés‐Colás, N., Garcia‐Molina, A., & Peñarrubia, L. (2007) · Plant Cell & Environment · doi:10.1111/j.1365-3040.2007.01642.x · Cited by 288 · see citing works
Charting the travels of copper in eukaryotes from yeast to mammals
Nevitt, T., Öhrvik, H., & Thiele, D. J. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2012.02.011 · Cited by 289 · see citing works
Eid, R., Arab, N. T. T., & Greenwood, M. T. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2016.12.002 · Cited by 286 · see citing works
Macrophages and Systemic Iron Homeostasis
Ganz, T. (2012) · Journal of Innate Immunity · doi:10.1159/000336423 · Cited by 281 · see citing works
The multifaceted role of iron in renal health and disease
van Swelm, R. P. L., Wetzels, J. F. M., & Swinkels, D. W. (2019) · Nature Reviews Nephrology · doi:10.1038/s41581-019-0197-5 · Cited by 279 · see citing works
Role of hypoxia-inducible factor-1 in transcriptional activation of ceruloplasmin by iron deficiency
Mukhopadhyay, C. K., Mazumder, B., & Fox, P. L. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m000636200 · Cited by 274 · see citing works
Lelièvre, P., Sancey, L., Coll, J., Deniaud, A., & Busser, B. (2020) · Cancers · doi:10.3390/cancers12123594 · Cited by 273 · see citing works
Importance of Iron Chelation in Free Radical-Induced Oxidative Stress and Human Disease
Jomová, K., & Valko, M. (2011) · Current Pharmaceutical Design · doi:10.2174/138161211798072463 · Cited by 271 · 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
Hahn, P., Qian, Y., Dentchev, T., Chen, L., Beard, J., Harris, Z. L., & Dunaief, J. L. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0405146101 · Cited by 264 · see citing works
Self-citationHahn, P. (2003) · Archives of Ophthalmology · doi:10.1001/archopht.121.8.1099 · Cited by 258 · see citing works
Iron homeostasis and toxicity in retinal degeneration
He, X., Hahn, P., Iacovelli, J., Wong, R., King, C., Bhisitkul, R., Massaro-Giordano, M., & Dunaief, J. L. (2007) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2007.07.004 · Cited by 260 · see citing works
Hepcidin and Its Role in Regulating Systemic Iron Metabolism
Ganz, T. (2006) · Hematology · doi:10.1182/asheducation-2006.1.29 · Cited by 260 · see citing works
Old iron, young copper: from Mars to Venus
Crichton, R. R., & Pierre, J.-L. (2001) · Biometals · doi:10.1023/a:1016710810701 · Cited by 248 · see citing works
Oxidative Stress and the Homeodynamics of Iron Metabolism
Bresgen, N., & Eckl, P. (2015) · Biomolecules · doi:10.3390/biom5020808 · Cited by 247 · see citing works
Copper handling machinery of the brain
Lutsenko, S., Bhattacharjee, A., & Hubbard, A. L. (2010) · Metallomics · doi:10.1039/c0mt00006j · Cited by 244 · see citing works
Brain iron metabolism: Neurobiology and neurochemistry
Ke, Y., & Qian, Z. (2007) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2007.07.009 · Cited by 236 · see citing works
The long history of iron in the Universe and in health and disease
Sheftel, A. D., Mason, A. B., & Ponka, P. (2011) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2011.08.002 · Cited by 235 · see citing works
Pregnancy and iron homeostasis: an update
Cao, C. Q., & O'Brien, K. O. (2013) · Nutrition Reviews · doi:10.1111/j.1753-4887.2012.00550.x · Cited by 235 · see citing works
Role of Iron in Neurodegenerative Disorders
Berg, D., & Youdim, M. B. H. (2006) · Topics in Magnetic Resonance Imaging · doi:10.1097/01.rmr.0000245461.90406.ad · Cited by 227 · see citing works
Galy, B., Ferring–Appel, D., Miñana, B., Bell, O., Janser, H., Muckenthaler, M. U., Schümann, K., & Hentze, M. W. (2005) · Blood · doi:10.1182/blood-2005-04-1365 · Cited by 222 · see citing works
The Yin and Yang of copper during infection
Besold, A. N., Culbertson, E. M., & Culotta, V. C. (2016) · JBIC Journal of Biological Inorganic Chemistry · doi:10.1007/s00775-016-1335-1 · Cited by 215 · see citing works
Iron Metabolism: Iron Deficiency and Iron Overload
Andrews, N. C. (2000) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.1.1.75 · Cited by 209 · see citing works
Structure to function relationships in ceruloplasmin: a 'moonlighting' protein
Bielli, P., & Calabrese, L. (2002) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-002-8519-2 · Cited by 211 · see citing works
Singh, N., Haldar, S., Tripathi, A. K., Horback, K., Wong, J., Sharma, D., Beserra, A., Suda, S., Anbalagan, C., Dev, S., et al. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2012.4931 · Cited by 205 · see citing works
Multi-Copper Oxidases and Human Iron Metabolism
Vashchenko, G., & MacGillivray, R. T. A. (2013) · Nutrients · doi:10.3390/nu5072289 · Cited by 212 · see citing works
Iron Regulation: Macrophages in Control
Sukhbaatar, N., & Weichhart, T. (2018) · Pharmaceuticals · doi:10.3390/ph11040137 · Cited by 201 · see citing works
Understanding iron homeostasis through genetic analysis of hemochromatosis and related disorders
Camaschella, C. (2005) · Blood · doi:10.1182/blood-2005-05-1857 · Cited by 194 · see citing works
Brain iron transport and neurodegeneration
Qian, Z., & Shen, X. (2001) · Trends in Molecular Medicine · doi:10.1016/s1471-4914(00)01910-9 · Cited by 196 · see citing works
Iron metabolism in Parkinsonian syndromes
Berg, D., & Hochstrasser, H. (2006) · Movement Disorders · doi:10.1002/mds.21020 · Cited by 185 · see citing works
Aydemir, T. B., Chang, S.-M., Guthrie, G. J., Maki, A. B., Ryu, M., Karabıyık, A., & Cousins, R. J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0048679 · Cited by 183 · see citing works
Graham, R. M. (2007) · World Journal of Gastroenterology · doi:10.3748/wjg.v13.i35.4725 · Cited by 180 · see citing works
Regulation of Iron Metabolism by Hepcidin under Conditions of Inflammation
Schmidt, P. J. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.r115.650150 · Cited by 181 · see citing works
Zhang, A., Xiong, S., Tsukamoto, H., & Enns, C. A. (2003) · Blood · doi:10.1182/blood-2003-07-2378 · Cited by 174 · see citing works
Iron homeostasis: new tales from the crypt
Roy, C. N., & Enns, C. A. (2000) · Blood · doi:10.1182/blood.v96.13.4020 · Cited by 175 · see citing works
Iron dysregulation in movement disorders
Dušek, P., Jankovic, J. J., & Le, W. (2012) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.12.054 · Cited by 172 · see citing works
Neurodegeneration with brain iron accumulation: update on pathogenic mechanisms
Levi, S., & Finazzi, D. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00099 · Cited by 164 · see citing works
Copper Availability Contributes to Iron Perturbations in Human Nonalcoholic Fatty Liver Disease
Aigner, E. S., Theurl, I., Haufe, H., Seifert, M., Hohla, F., Scharinger, L., Stickel, F., Mourlane, F., Weiß, G., & Datz, C. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.04.007 · Cited by 163 · see citing works
The Regulation of Cellular Iron Metabolism
Chua, A. C. G., Graham, R. M., Trinder, D., & Olynyk, J. K. (2007) · Critical Reviews in Clinical Laboratory Sciences · doi:10.1080/10408360701428257 · Cited by 168 · see citing works
The copper-iron chronicles: The story of an intimate relationship
Fox, P. L. (2003) · BioMetals · doi:10.1023/a:1020799512190 · Cited by 166 · see citing works
Iron and leukemia: new insights for future treatments
Wang, F., Lv, H., Zhao, B., Zhou, L., Wang, S., Luo, J., Liu, J., & Shang, P. (2019) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-019-1397-3 · Cited by 170 · see citing works
Intersection of Iron and Copper Metabolism in the Mammalian Intestine and Liver
Doğuer, Ç., Ha, J., & Collins, J. F. (2018) · Comprehensive physiology · doi:10.1002/cphy.c170045 · Cited by 214 · see citing works
Iron transport proteins: Gateways of cellular and systemic iron homeostasis
Knutson, M. D. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.r117.786632 · Cited by 163 · see citing works
Hephaestin is a ferroxidase that maintains partial activity in sex-linked anemia mice
Chen, H. (2004) · Blood · doi:10.1182/blood-2003-09-3139 · Cited by 165 · see citing works
Ayton, S., & Lei, P. (2014) · BioMed Research International · doi:10.1155/2014/581256 · Cited by 161 · see citing works
Aceruloplasminemia: An Inherited Neurodegenerative Disease with Impairment of Iron Homeostasis
XU, X., PIN, S., GATHINJI, M., FUCHS, R., & HARRIS, Z. L. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1306.024 · Cited by 160 · see citing works
Self-citationUnexpected role of ceruloplasmin in intestinal iron absorption
Cherukuri, S., Potla, R., Sarkar, J., Nurko, S., Harris, Z. L., & Fox, P. L. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.10.003 · Cited by 158 · see citing works
Self-citationNg, S., Norwitz, S. G., & Norwitz, E. R. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20133283 · Cited by 158 · see citing works
Mechanism of Copper Uptake from Blood Plasma Ceruloplasmin by Mammalian Cells
Ramos, D., Mar, D., Ishida, M., Vargas, R. E., Gaite, M., Montgomery, A. P., & Linder, M. C. (2016) · PLoS ONE · doi:10.1371/journal.pone.0149516 · Cited by 156 · see citing works
Molecular basis of inherited microcytic anemia due to defects in iron acquisition or heme synthesis
Iolascon, A., Falco, L. D., & Beaumont, C. (2009) · Haematologica · doi:10.3324/haematol.13619 · Cited by 153 · see citing works
Ceruloplasmin in neurodegenerative diseases
Vassiliev, V. B., Harris, Z. L., & Zatta, P. F. (2005) · Brain Research Reviews · doi:10.1016/j.brainresrev.2005.03.003 · Cited by 148 · see citing works
Self-citationKim, C., Lorenz, W. W., Hoopes, J. T., & Dean, J. F. D. (2001) · Journal of Bacteriology · doi:10.1128/jb.183.16.4866-4875.2001 · Cited by 149 · see citing works
Jeong, S. Y., & David, S. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.2922-06.2006 · Cited by 148 · see citing works
Copper storage diseases: Menkes, Wilson's, and Cancer
Kenyon, G. L. (2004) · Frontiers in bioscience · doi:10.2741/1424 · Cited by 146 · see citing works
Mammalian iron transporters: Families SLC11 and SLC40
Montalbetti, N., Simonin, A., Kovács, G., & Hediger, M. A. (2013) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2013.01.002 · Cited by 147 · see citing works
Basic and Clinical Aspects of Copper
Harris, E. D. (2003) · Critical Reviews in Clinical Laboratory Sciences · doi:10.1080/10408360390250649 · Cited by 154 · see citing works
- Authors
- Harris, Z. L., Durley, A. P., Man, T. K., & Gitlin, J. D.
- Affiliations
- Washington University in St. Louis (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1999-09-14
- Volume
- 96
- Issue
- 19
- Pages
- 10812-10817
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC17965
- OpenAlex
- W2104657893
- Cited by
- 568
- References
- 40
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 10 · 2023: 13 · 2022: 16 · 2021: 17 · 2020: 20 · 2019: 17 · 2018: 20 · 2017: 14 · 2016: 17 · 2015: 14 · 2014: 18 · 2013: 13 · 2012: 24
- FWCI
- 15.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1p30hd033688-01, 5r01hl041536-13, 5k08dk002464-04, DK02464, HL41536)
- National Heart, Lung, and Blood Institute (HL41536)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK02464)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 33688)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Keywords
- ceruloplasmin, aceruloplasminemia, iron efflux, cellular iron homeostasis, iron accumulation, iron metabolism, ferrokinetics, reticuloendothelial cells, hepatocytes, serum ferritin, iron storage
- MeSH terms
- Animals, Apoproteins, Ceruloplasmin, Disease Models, Animal, Homeostasis, Iron, Liver, Metal Metabolism, Inborn Errors, Models, Genetic, Phenotype, Spleen, Time Factors, Mutagenesis, Insertional, Neurodegenerative Diseases, Mice
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
