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Ceruloplasmin Regulates Iron Levels in the CNS and Prevents Free Radical Injury
Open accessAbstract
Ceruloplasmin is a ferroxidase that oxidizes toxic ferrous iron to its nontoxic ferric form. We have previously reported that a glycosylphosphatidylinositol-anchored form of ceruloplasmin is expressed in the mammalian CNS. To better understand the role of ceruloplasmin in iron homeostasis in the CNS, we generated a ceruloplasmin gene-deficient (Cp(-/-)) mouse. Adult Cp(-/-) mice showed increased iron deposition in several regions of the CNS such as the cerebellum and brainstem. Increased lipid peroxidation was also seen in some CNS regions. Cerebellar cells from neonatal Cp(-/-) mice were also more susceptible to oxidative stress in vitro. Cp(-/-) mice showed deficits in motor coordination that were associated with a loss of brainstem dopaminergic neurons. These results indicate that ceruloplasmin plays an important role in maintaining iron homeostasis in the CNS and in protecting the CNS from iron-mediated free radical injury. Therefore, the antioxidant effects of ceruloplasmin could have important implications for various neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease in which iron deposition is known to occur.
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In the citing paper
“Ceruloplasmin dysfunction might be associated with Parkinson’s disease.135,136”
From The role of iron in brain ageing and neurodegenerative disorders (2014) · cites this paper as [135]
In the citing paper
“Ferritin H is induced by NF-κB in response to TNF-α treatment, resulting in suppression of ROS and inhibition of apoptosis (243).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [243]
In the citing paper
“NF-κB is activated by TNF-α and has been shown to induce mouse and human ferritin H (171, 243).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [243]
In the citing paper
“Ferritin H was found as a TNF-α– or IL-1–inducible gene (171, 243, 294).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [243]
In the citing paper
“Apoptosis induced by TNF-α was inhibited by NF-κB”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [243]
In the citing paper
“Many studies set a precedent of ferritin in cytoprotection against free-iron–catalyzed production of ROS (227, 243, 301).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [243]
In the citing paper
“Ferritin was identified as the downstream mediator of the antioxidant and protective activities of NF-κB in response to TNF-α signaling in inflammation and apoptosis (243, 294).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [243]
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Citations
Cites
Hansen, M., Nielsen, S. E., & Berg, K. (1989) · Journal of Immunological Methods · doi:10.1016/0022-1759(89)90397-9 · Cited by 3,488
Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter
Donovan, A., Brownlie, A., Zhou, Y., Shepard, J., Pratt, S. J., Moynihan, J., Paw, B. H., Drejer, A., Barut, B., Zapata, A., et al. (2000) · Nature · doi:10.1038/35001596 · Cited by 1,667
McKie, A. T., Marciani, P., Rolfs, A., Brennan, K., Wehr, K., Barrow, D., Miret, S., Bomford, A., Peters, T. J., Farzaneh, F., et al. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)80425-6 · Cited by 1,422
Toxicity of iron and hydrogen peroxide: the Fenton reaction
Winterbourn, C. C. (1995) · Toxicology Letters · doi:10.1016/0378-4274(95)03532-x · Cited by 1,415
Iron accumulation in Alzheimer disease is a source of redox-generated free radicals
Smith, M. A., Harris, P. L. R., Sayre, L. M., & Perry, G. L. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.18.9866 · Cited by 1,365
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
A radical hypothesis for neurodegeneration
Olanow, C. W. (1993) · Trends in Neurosciences · doi:10.1016/0166-2236(93)90070-3 · Cited by 722
Altered Brain Metabolism of Iron as a Cause of Neurodegenerative Diseases?
Gerlach, M., Ben‐Shachar, D., Riederer, P. F., & Youdim, M. B. H. (1994) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1994.63030793.x · Cited by 704
Frey, D., Schneider, C., Xu, L., Borg, J., Spooren, W. P. J. M., & Caroni, P. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-07-02534.2000 · Cited by 683
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
Gene Targeting: A Practical Approach
Hirst, M. C. (1994) · Journal of Medical Genetics · doi:10.1136/jmg.31.10.821-a · Cited by 587
Gene targeting: a practical approach.
Joyner, A. L. (1993) · Cited by 575
Targeted gene disruption reveals an essential role for ceruloplasmin in cellular iron efflux
Harris, Z. L., Durley, A. P., Man, T. K., & Gitlin, J. D. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.19.10812 · Cited by 568
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 · cited 2×
“The iron deposition seen in these mice is similar in some respects to that observed in patients with aceruloplasminemia, because these patients also display iron accumulation in the brainstem, cerebellum, and retina (Miyajima et al., 1987; Harris et al., 1995; Morita et al., 1995; Yoshida et al., 1995).”
ResultCellular Construction of a Circadian Clock: Period Determination in the Suprachiasmatic Nuclei
Liu, C., Weaver, D. R., Strogatz, S. H., & Reppert, S. M. (1997) · Cell · doi:10.1016/s0092-8674(00)80473-0 · Cited by 508
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
Hyslop, P. A., Zhang, Z., Pearson, D. V., & Phebus, L. A. (1995) · Brain Research · doi:10.1016/0006-8993(94)01291-o · Cited by 338
Patel, B. N., & David, S. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.32.20185 · Cited by 327
Self-citationFamilial 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
Andrews, N. C. (1999) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/s1357-2725(99)00065-5 · Cited by 251
Morita, 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
Torrance, J. D. (1980) · Medical Entomology and Zoology · Cited by 234
Ousman, S. S., & David, S. (2000) · Glia · doi:10.1002/(sici)1098-1136(200003)30:1 · Cited by 209
Self-citationPatel, B. N., Dunn, R. J., & David, S. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.6.4305 · Cited by 202
Self-citationCeruloplasmin 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
Iron and oxygen radicals in brain
Gutteridge, J. M. C. (1992) · Annals of Neurology · doi:10.1002/ana.410320705 · Cited by 191
Hussain, S. M., Slikker, W., & Ali, S. F. (1995) · International Journal of Developmental Neuroscience · doi:10.1016/0736-5748(95)00071-2 · Cited by 186
Bowie, A., Moynagh, P. N., & O'Neill, L. A. J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.41.25941 · Cited by 185
Molecular mechanisms of iron uptake in eukaryotes
de Silva, D. M., Askwith, C. C., & Kaplan, J. (1996) · Physiological Reviews · doi:10.1152/physrev.1996.76.1.31 · Cited by 182
Klomp, L. W. J. (1996) · Human Molecular Genetics · doi:10.1093/hmg/5.12.1989 · Cited by 161
Gitlin, J. D. (1998) · Pediatric Research · doi:10.1203/00006450-199809000-00001 · Cited by 140
Fleming, R. E., & Gitlin, J. D. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)39171-9 · Cited by 138
Existing and emerging mechanisms for transport of iron and manganese to the brain
Malecki, E. A., Devenyi, A. G., Beard, J. L., & Connor, J. R. (1999) · Journal of Neuroscience Research · doi:10.1002/(sici)1097-4547(19990415)56:2 · Cited by 138
Frazer, D. M., Vulpe, C. D., McKie, A. T., Wilkins, S. J., Trinder, D., Cleghorn, G. J., & Anderson, G. J. (2001) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.2001.281.4.g931 · Cited by 137
Hereditary ceruloplasmin deficiency with hemosiderosis
Okamoto, N., Wada, S., Oga, T., Kawabata, Y., Baba, Y., Habu, D., Takeda, Z., & Wada, Y. (1996) · Human Genetics · doi:10.1007/bf02346185 · Cited by 112
Surai, P. F., Speake, B. K., Noble, R. C., & Sparks, N. H. C. (1999) · Biological Trace Element Research · doi:10.1007/bf02784397 · Cited by 103
Ceruloplasmin levels in the human superior temporal gyrus in aging and Alzheimer's disease
Connor, J. R., Tucker, P., Johnson, M. J., & Snyder, B. S. (1993) · Neuroscience Letters · doi:10.1016/0304-3940(93)90805-u · Cited by 95
Reduced ferroxidase activity in the cerebrospinal fluid from patients with Parkinson's disease
Boll, M.-C., Sotelo, J., Otero, E., Alcaraz-Zubeldia, M., & Rios, C. (1999) · Neuroscience Letters · doi:10.1016/s0304-3940(99)00221-9 · Cited by 92
Biochemical Analysis of a Missense Mutation in Aceruloplasminemia
Hellman, N. E., Kono, S., Miyajima, H., & Gitlin, J. D. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109123200 · Cited by 84
Borg, D. C., & Schaich, K. M. (1986) · Journal of Free Radicals in Biology & Medicine · doi:10.1016/s0748-5514(86)80004-6 · Cited by 70
Manganese uptake into rat brain during development and aging
Takeda, A., Ishiwatari, S., & Okada, S. (1999) · Journal of Neuroscience Research · doi:10.1002/(sici)1097-4547(19990401)56:1 · Cited by 69
Role 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
Ceruloplasmin, transferrin and apotransferrin facilitate iron release from human liver cells
Young, S. P., Fahmy, M., & Golding, S. (1997) · FEBS Letters · doi:10.1016/s0014-5793(97)00478-x · Cited by 57
Regulation and developmental expression of the divalent metal-ion transporter in the rat brain.
Williams, K. E., Ma, W., & Bressler, J. P. (2000) · PubMed · Cited by 48
Fragmentation of human ceruloplasmin induced by hydrogen peroxide
Choi, S.-W. (2000) · Biochimie · doi:10.1016/s0300-9084(00)00380-1 · Cited by 47
Expression of ceruloplasmin in the retina: induction after optic nerve crush.
Levin, L. A., & Geszvain, K. (1998) · PubMed · Cited by 43
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
Characterization of “plasma proteins” secreted by cultured rat macroglial cells
Zahs, K. R., Bigornia, V., & Deschepper, C. F. (1993) · Glia · doi:10.1002/glia.440070202 · Cited by 30
Iron deficiency alters H- and L-ferritin expression in rat brain.
Han, J., Day, J. R., Thomson, K. A., Connor, J. R., & Beard, J. L. (2000) · PubMed · Cited by 30
Using Genetic Mutations to Study the Neural Basis of Behavior
Steele, P. M., Medina, J. F., Nores, W. L., & Mauk, M. D. (1998) · Cell · doi:10.1016/s0092-8674(00)81712-2 · Cited by 24
Hereditary ceruloplasmin deficiency with hemosiderosis
Okamoto, N., Wada, S., Oga, T., et al. (1996) · Human Genetics · doi:10.1007/s004390050132 · Cited by 21
Mittal, B., & David, S. (1994) · Molecular and Cellular Neuroscience · doi:10.1006/mcne.1994.1006 · Cited by 12
Self-citation
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Ward, R. J., Zucca, F. A., Duyn, J. H., Crichton, R. R., & Zecca, L. (2014) · The Lancet Neurology · doi:10.1016/s1474-4422(14)70117-6 · Cited by 1,819
Current research on acute phase proteins in veterinary diagnosis: an overview
Murata, H., Shimada, N., & Yoshioka, M. (2003) · The Veterinary Journal · doi:10.1016/s1090-0233(03)00119-9 · Cited by 1,108
Duce, J. A., Tsatsanis, A., Cater, M. A., James, S., Robb, E. L., Wikhe, K., Leong, S. L., Perez, K. A., Johanssen, T., Greenough, M. A., et al. (2010) · Cell · doi:10.1016/j.cell.2010.08.014 · Cited by 695
Iron neurochemistry in Alzheimer's disease and Parkinson's disease: targets for therapeutics
Belaidi, A. A., & Bush, A. I. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13425 · Cited by 594
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
Metadata
- Authors
- Patel, B. N., Dunn, R. J., Jeong, S. Y., Zhu, Q., Julien, J.-P., & David, S.
- Affiliations
- Montreal General Hospital (CA)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2002-08-01
- Volume
- 22
- Issue
- 15
- Pages
- 6578-6586
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6758125
- OpenAlex
- W1595395957
- Cited by
- 379
- References
- 51
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 10 · 2023: 12 · 2022: 16 · 2021: 14 · 2020: 12 · 2019: 11 · 2018: 22 · 2017: 17 · 2016: 11 · 2015: 24 · 2014: 24 · 2013: 15 · 2012: 22
- FWCI
- 10.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Parkinson's Disease Foundation
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Keywords
- ceruloplasmin, iron homeostasis, central nervous system, ferroxidase, oxidative damage, oxidative stress, lipid peroxidation, cerebellum, brainstem, dopaminergic neurons, motor coordination deficits, neurodegenerative diseases, Parkinson's disease, Alzheimer's disease, iron accumulation
- MeSH terms
- Animals, Astrocytes, Brain Stem, Cell Survival, Cells, Cultured, Central Nervous System, Ceruloplasmin, Disease Models, Animal, Free Radicals, Iron, Liver, Neurons, Transferrin, Lipid Peroxidation, Mice, Knockout, Oxidative Stress, Gene Targeting, Motor Skills Disorders, Mice
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