Isoforms of ferritin have a specific cellular distribution in the brain
Abstract
Ferritin is the major iron storage protein and accounts for the majority of the iron in the brain. Thus, ferritin is a key component in protecting the brain from iron induced oxidative damage. The high lipid content, high rate of oxidative metabolism, and high iron content combine to make the brain the organ most susceptible to oxidative stress. The role of oxidative damage and disruption of brain iron homeostasis is considered clinically important to normal aging and a potential pathogenic component of a number of neurologic disorders including Alzheimer's disease and Parkinson's disease. Little is known, however, of the mechanism by which the brain maintains iron homeostasis at either the whole organ or cellular level. In this study we report the cellular distribution of the two isoforms of ferritin in the brain of adult subhuman primates. A subset of neurons immunolabel specifically for the H‐chain ferritin protein, whereas cells resembling microglia are immunolabeled only after exposure to the L‐chain ferritin antibody. Only one cell type immunostains for both H‐and L‐chain ferritin; these cells are morphologically similar and have the same distribution pattern as oligodendrocytes. Neither ferritin isoform is usually detected in astrocytes. These data indicate considerable differences in iron sequestration and use between neurons and glia and among neuronal and glial subtypes. This information will be essential in determining the role of each of these cells in maintaining general brain iron homeostasis and the relative abilities of these cells to withstand oxidative stress. © 1994 Wiley‐Liss, Inc.
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Increased incidence of arthritis is observed in HH.
“Increased incidence of arthritis also is observed in HH (54).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [54]
Cites
Heavy metal intensification of DAB-based HRP reaction product.
Adams, J. C. (1981) · Journal of Histochemistry & Cytochemistry · doi:10.1177/29.6.7252134 · Cited by 1,812 · see citing works
The effect of age on the non-haemin iron in the human brain
Hallgren, B., & Sourander, P. (1958) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1958.tb12607.x · Cited by 1,427 · see citing works
Transition metals, ferritin, glutathione, and ascorbic acid in parkinsonian brains
Riederer, P., Sofic, E., Rausch, W., Schmidt, B., Reynolds, G. P., Jellinger, K., & Youdim, M. B. H. (1989) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1989.tb09150.x · Cited by 1,383 · see citing works
Ferritin: a cytoprotective antioxidant strategem of endothelium.
Balla, G., Jacob, H., Balla, J., Rosenberg, M. E., Nath, K. A., Apple, F., Eaton, J. W., & Vercellotti, G. M. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)37165-0 · Cited by 1,097 · see citing works
Eng, L. F. (1985) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(85)80063-1 · Cited by 737 · see citing works
The regional distribution and cellular localization of iron in the rat brain
Hill, J. M., & Switzer, R. C. (1984) · Neuroscience · doi:10.1016/0306-4522(84)90046-0 · Cited by 486 · see citing works
Cellular distribution of transferrin, ferritin, and iron in normal and aged human brains
Connor, J. R., Menzies, S. L., Martin, S. M. S., & Mufson, E. J. (1990) · Journal of Neuroscience Research · doi:10.1002/jnr.490270421 · Cited by 472 · see citing works
Self-citationA histochemical study of iron, transferrin, and ferritin in Alzheimer's diseased brains
Connor, J. R., Menzies, S. L., Martin, S. M. S., & Mufson, E. J. (1992) · Journal of Neuroscience Research · doi:10.1002/jnr.490310111 · Cited by 468 · see citing works
Self-citationConnor, J. R., Snyder, B. S., Beard, J. L., Fine, R. E., & Mufson, E. J. (1992) · Journal of Neuroscience Research · doi:10.1002/jnr.490310214 · Cited by 374 · see citing works
Self-citationDecreased ferritin levels in brain in Parkinson's disease
Dexter, D. T., Carayon, A., Vidailhet, M., Ruberg, M., Agid, F., Agid, Y., Lees, A. J., Wells, F. R., Jenner, P., & Marsden, C. D. (1990) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1990.tb08814.x · Cited by 258 · see citing works
Ferritin, transferrin, and iron in selected regions of the adult and aged rat brain
Benkovic, S. A., & Connor, J. R. (1993) · The Journal of Comparative Neurology · doi:10.1002/cne.903380108 · Cited by 238 · see citing works
Self-citationIron regulation in the brain: Histochemical, biochemical, and molecular considerations
Connor, J. R., & Benkovic, S. A. (1992) · Annals of Neurology · doi:10.1002/ana.410320710 · Cited by 178 · see citing works
Self-citationFerritin immunohistochemistry as a marker for microglia
Kaneko, Y., Kitamoto, T., Tateishi, J., & Yamaguchi, K. (1989) · Acta Neuropathologica · doi:10.1007/bf00294369 · Cited by 153 · see citing works
Ferritin: isolation of aluminum-ferritin complex from brain.
Fleming, J. T., & Joshi, J. G. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.22.7866 · Cited by 149 · see citing works
Iron uptake and utilization by mammalian cells. I: Cellular uptake of transferrin and iron
Octave, J., Schneider, Y., Trouet, A., & Crichton, R. R. (1983) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(83)90217-7 · Cited by 136 · see citing works
Dallman, P. R., & Spirito, R. A. (1977) · Journal of Nutrition · doi:10.1093/jn/107.6.1075 · Cited by 126 · see citing works
Dedman, D., Treffry, A., Candy, J., Taylor, G. A., Morris, C. M., Bloxham, C. A., Perry, R. H., Edwardson, J. A., & Harrison, P. M. (1992) · Biochemical Journal · doi:10.1042/bj2870509 · Cited by 121 · see citing works
Immunochemical characterization of human liver and heart ferritins with monoclonal antibodies
Luzzago, A., Arosio, P., Iacobello, C., Ruggeri, G., Capucci, L., Brocchi, E., Simone, F., Gamba, D., Gabri, E., Levi, S., et al. (1986) · Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology · doi:10.1016/0167-4838(86)90147-0 · Cited by 93 · see citing works
Experimental Superficial Siderosis of the Central Nervous System. I. Morphological Observations
Koeppen, A. H., & Borke, R. C. (1991) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199109000-00005 · Cited by 91 · see citing works
Human Ferritin Gene Expression
Drysdale, J. W. (1988) · Progress in nucleic acid research and molecular biology · doi:10.1016/s0079-6603(08)60612-1 · Cited by 55 · see citing works
Cairo, G., Rappocciolo, E., Tacchini, L., & Schiaffonati, L. (1991) · Biochemical Journal · doi:10.1042/bj2750813 · Cited by 54 · see citing works
Ferritin: An expanded role in metabolic regulation
Joshi, J. G., & Zimmerman, A. (1988) · Toxicology · doi:10.1016/0300-483x(88)90055-8 · Cited by 45 · see citing works
Structural and Functional Studies of Human Ferritin H and L Chains1
Arosio, P., Levi, S., Santambrogio, P., et al. (2015) · Current studies in hematology and blood transfusion · doi:10.1159/000419350 · Cited by 39 · see citing works
Biotechnology of Plasma Proteins
Lundblad, R. L. (2012) · CRC Press eBooks · doi:10.1201/b12368 · Cited by 37 · see citing works
Identification of two human ferritin H genes on the short arm of chromosome 6
Dugast, I., Papadopoulos, P., Zappone, E., Jones, C., Theriault, K., Handelman, G. J., Bénarous, R., & Drysdale, J. (1990) · Genomics · doi:10.1016/0888-7543(90)90558-c · Cited by 25 · see citing works
Cammer, W., Sacchi, R., Kahn, S., & Sapirstein, V. S. (1985) · Journal of Neuroscience Research · doi:10.1002/jnr.490140303 · Cited by 25 · see citing works
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Swain, R. A., Harris, A. B., Wiener, E. C., Dutka, M. V., Morris, H. D., Theien, B. E., Konda, S., Engberg, K., Lauterbur, P. C., & Greenough, W. T. (2003) · Neuroscience · doi:10.1016/s0306-4522(02)00664-4 · Cited by 655 · see citing works
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Kaur, D., Yantiri, F., Rajagopalan, S., Kumar, J., Mo, J. Q., Boonplueang, R., Viswanath, V., Jacobs, R., Yang, L., Beal, M. F., et al. (2003) · Neuron · doi:10.1016/s0896-6273(03)00126-0 · Cited by 620 · see citing works
Rogers, J. T., Randall, J. D., Cahill, C. M., Eder, P. S., Huang, X., Gunshin, H., Leiter, L., McPhee, J., Sarang, S. S., Utsuki, T., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m207435200 · Cited by 551 · see citing works
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Connor, J. R., Boyer, P. J., Menzies, S. L., Dellinger, B., Allen, R. P., Ondo, W. G., & Earley, C. J. (2003) · Neurology · doi:10.1212/01.wnl.0000078887.16593.12 · Cited by 548 · see citing works
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Mackenzie, E. L., Iwasaki, K., & Tsuji, Y. (2008) · Antioxidants & Redox Signaling · doi:10.1089/ars.2007.1893 · Cited by 526 · see citing works
Zecca, L., Gallorini, M., Schünemann, V., Trautwein, A. X., Gerlach, M., Riederer, P., Vezzoni, P., & Tampellini, D. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00186.x · Cited by 401 · 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
Lopes, K. O., Sparks, D. L., & Streit, W. J. (2008) · Glia · doi:10.1002/glia.20678 · Cited by 262 · see citing works
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Oakley, A. E., Collingwood, J. F., Dobson, J., Love, G., Perrott, H. R., Edwardson, J. A., Elstner, M., & Morris, C. M. (2007) · Neurology · doi:10.1212/01.wnl.0000262033.01945.9a · Cited by 273 · see citing works
Zecca, L., Berg, D., Arzberger, T., Ruprecht, P., Rausch, W. D., Musicco, M., Tampellini, D., Riederer, P., Gerlach, M., & Becker, G. (2005) · Movement Disorders · doi:10.1002/mds.20550 · Cited by 214 · see citing works
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Meadowcroft, M. D., Connor, J. R., & Yang, Q. X. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00255 · Cited by 51 · see citing works
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Self-citation
- Authors
- Connor, J. R., Boeshore, K. L., Benkovic, S. A., & Menzies, S. L.
- Affiliations
- Pennsylvania State University (US)
- Corresponding author
- Connor, J. R.
- Venue
- Journal of Neuroscience Research
- Publisher
- Wiley
- Published
- 1994-03
- Volume
- 37
- Issue
- 4
- Pages
- 461-465
- ISSN
- 0360-4012 (ISSN-L)
- 1097-4547
- OpenAlex
- W2077740413
- Cited by
- 179
- References
- 26
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 8 · 2023: 8 · 2022: 3 · 2021: 7 · 2020: 6 · 2019: 4 · 2018: 2 · 2017: 3 · 2016: 6 · 2015: 7 · 2014: 3 · 2013: 6 · 2012: 4
- FWCI
- 2.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuroscience Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ag009063-03)
- U.S. Public Health Service
- National Institute on Aging (AG09063)
- 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
- ferritin, brain iron homeostasis, iron storage, oxidative stress, neurons, microglia, oligodendrocytes, astrocytes, subhuman primates, neurodegenerative diseases, Alzheimer's disease, Parkinson's disease
- MeSH terms
- Animals, Antibodies, Monoclonal, Brain, Brain Chemistry, Ferritins, Homeostasis, Iron, Macaca, Nerve Tissue Proteins, Neurons, Oligodendroglia, Organ Specificity, Microglia
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