The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
Analysis of the biologic functions of H- and L-ferritins in HeLa cells by transfection with siRNAs and cDNAs: evidence for a proliferative role of L-ferritin
Open accessAbstract
We describe the use of small interfering RNAs (siRNAs) to down-regulate H- and L-ferritin levels in HeLa cells. siRNAs repressed H- and L-ferritin expression to about 20% to 25% of the background level in both stable and transient transfections. HeLa cells transfected with H- and L-ferritin cDNAs were analyzed in parallel to compare the effects of ferritin up- and down-regulation. We found that large modifications of L-ferritin levels did not affect iron availability in HeLa cells but positively affected cell proliferation rate in an iron-independent manner. The transient down-regulation of H-ferritin modified cellular iron availability and resistance to oxidative damage, as expected. In contrast, the stable suppression of H-ferritin in HeLa cell clones transfected with siRNAs did not increase cellular iron availability but made cells less resistant to iron supplementation and chelation. The results indicate that L-ferritin has no direct effects on cellular iron homeostasis in HeLa cells, while it has new, iron-unrelated functions. In addition, they suggest that H-ferritin function is to act as an iron buffer.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
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?
In the citing paper
“In addition, HeLa cells that express mutant ferritin L chains exhibited a phenotype of iron loading (61).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [61]
In the citing paper
“Studies with recombinant mutant ferritin L showed that, although it was able to assemble into 24-subunit ferritin shells, the efficiency of assembly and capacity to incorporate iron were both decreased in vitro (61).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [61]
Citations
Cites
A System for Stable Expression of Short Interfering RNAs in Mammalian Cells
Brummelkamp, T. R., Bernards, R., & Agami, R. (2002) · Science · doi:10.1126/science.1068999 · Cited by 4,295
The ferritins: molecular properties, iron storage function and cellular regulation
Harrison, P. M., & Arosio, P. (1996) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(96)00022-9 · Cited by 2,667
Self-citationHentze, M. W., & Kühn, L. C. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.16.8175 · Cited by 1,292
Killing the messenger: short RNAs that silence gene expression
Dykxhoorn, D. M., Novina, C. D., & Sharp, P. A. (2003) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1129 · Cited by 1,185
Mineralization in ferritin: an efficient means of iron storage
Chasteen, N. D., & Harrison, P. M. (1999) · Journal of Structural Biology · doi:10.1006/jsbi.1999.4118 · Cited by 815
Solving the structure of human H ferritin by genetically engineering intermolecular crystal contacts
Lawson, D. M., Artymiuk, P. J., Yewdall, S. J., Smith, J. M. A., Livingstone, J. C., Treffry, A., Luzzago, A., Levi, S., Arosio, P., Cesareni, G., et al. (1991) · Nature · doi:10.1038/349541a0 · Cited by 777
Self-citationArosio, P., & Levi, S. (2002) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(02)00842-0 · Cited by 553
Self-citationCurtis, A. R. J., Fey, C., Morris, C. M., Bindoff, L. A., Ince, P. G., Chinnery, P. F., Coulthard, A., Jackson, M. J., Jackson, A. P., McHale, D. P., et al. (2001) · Nature Genetics · doi:10.1038/ng571 · Cited by 537
Ferritin and the response to oxidative stress
ORINO, K., LEHMAN, L., TSUJI, Y., AYAKI, H., TORTI, S. V., & TORTI, F. M. (2001) · Biochemical Journal · doi:10.1042/bj3570241 · Cited by 535
A human mitochondrial ferritin encoded by an intronless gene
Levi, S., Corsi, B., Bosisio, M., Invernizzi, R., Volz, A., Sanford, D., Arosio, P., & Drysdale, J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.c100141200 · Cited by 400
Self-citationBeaumont, C., Leneuve, P., Devaux, I., Scoazec, J.-Y., Berthier, M., Loiseau, M.-N., Grandchamp, B., & Bonneau, D. (1995) · Nature Genetics · doi:10.1038/ng1295-444 · Cited by 293
RNA interference in mammalian cells using siRNAs synthesized with T7 RNA polymerase
Donzé, O. (2002) · Nucleic Acids Research · doi:10.1093/nar/30.10.e46 · Cited by 275
Overexpression of Wild Type and Mutated Human Ferritin H-chain in HeLa Cells
Cozzi, A., Corsi, B., Levi, S., Santambrogio, P., Albertini, A., & Arosio, P. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m003797200 · Cited by 242
Self-citationFerritin: At the Crossroads of Iron and Oxygen Metabolism
Theil, E. C. (2003) · Journal of Nutrition · doi:10.1093/jn/133.5.1549s · Cited by 240
Edbauer, D., Winkler, E., Haass, C., & Steiner, H. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.132277899 · Cited by 224
White, K., & Munro, H. N. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)68398-x · Cited by 208
Role for NF-κB in the regulation of ferritin H by tumor necrosis factor-α
Kwak, E. L., Larochelle, D. A., Beaumont, C., Torti, S. V., & Torti, F. M. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.25.15285 · Cited by 189
Cook, T. A., Gebelein, B. A., Mesa, K., Mladek, A. C., & Urrutia, R. A. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.40.25929 · Cited by 189
The Role of the L-Chain in Ferritin Iron Incorporation
Levi, S., Santambrogio, P., Cozzi, A., Rovida, E., Corsi, B., Tamborini, E., Spada, S., Albertini, A., & Arosio, P. (1994) · Journal of Molecular Biology · doi:10.1006/jmbi.1994.1325 · Cited by 180
Self-citationMitochondrial Ferritin: A New Player in Iron Metabolism
Drysdale, J., Arosio, P., Invernizzi, R., Cazzola, M., Volz, A., Corsi, B., Biasiotto, G., & Levi, S. (2002) · Blood Cells, Molecules, and Diseases · doi:10.1006/bcmd.2002.0577 · Cited by 180
Self-citationCombinatorial mRNA Regulation: Iron Regulatory Proteins and Iso-iron-responsive Elements (Iso-IREs)
Theil, E. C., & Eisenstein, R. S. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.r000019200 · Cited by 162
Multiple Pathways for Mineral Core Formation in Mammalian Apoferritin. The Role of Hydrogen Peroxide
Zhao, G., Bou‐Abdallah, F., Arosio, P., Levi, S., Janus-Chandler, C., & Chasteen, N. D. (2003) · Biochemistry · doi:10.1021/bi027357v · Cited by 155
Self-citationKulp, K. S., Green, S. L., & Vulliet, P. R. (1996) · Experimental Cell Research · doi:10.1006/excr.1996.0343 · Cited by 103
Kakhlon, O., Gruenbaum, Y., & Cabantchik, Z. I. (2001) · Blood · doi:10.1182/blood.v97.9.2863 · Cited by 97
Levi, S., Girelli, D., Perrone, F., Pasti, M., Beaumont, C., Corrocher, R., Albertini, A., & Arosio, P. (1998) · Blood · doi:10.1182/blood.v91.11.4180 · Cited by 96
Self-citationH ferritin knockout mice: a model of hyperferritinemia in the absence of iron overload
Ferreira, C., Santambrogio, P., Martin, M.-E., Andrieu, V., Feldmann, G., Hénin, D., & Beaumont, C. (2001) · Blood · doi:10.1182/blood.v98.3.525 · Cited by 89
Self-citationPicard, V., Renaudie, F., Porcher, C., Hentze, M. W., Grandchamp, B., & Beaumont, C. (1996) · Blood · doi:10.1182/blood.v87.5.2057.2057 · Cited by 89
Activation of Caspase Pathways during Iron Chelator-mediated Apoptosis
Greene, B. T., Thorburn, J., Willingham, M. C., Thorburn, A. M., Planalp, R. P., Brechbiel, M. W., Jennings‐Gee, J. E., Wilkinson, J. C., Torti, F. M., & Torti, S. V. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m110345200 · Cited by 77
Role of iron and ferritin in TNFα‐induced apoptosis in HeLa cells
Cozzi, A., Levi, S., Corsi, B., Santambrogio, P., Campanella, A., Gerardi, G., & Arosio, P. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)00114-5 · Cited by 76
Self-citationGirelli, D., Bozzini, C., Zecchina, G., Tinazzi, E., Bosio, S., Piperno, A., Ramenghi, U., Peters, J., Levi, S., Camaschella, C., et al. (2001) · British Journal of Haematology · doi:10.1046/j.1365-2141.2001.03116.x · Cited by 69
Self-citationMumford, A. D. (2000) · British Journal of Ophthalmology · doi:10.1136/bjo.84.7.697 · Cited by 60
Repression of the heavy ferritin chain increases the labile iron pool of human K562 cells
Kakhlon, O., Gruenbaum, Y., & Cabantchik, Z. I. (2001) · Biochemical Journal · doi:10.1042/0264-6021:3560311 · Cited by 59
The IRE (iron regulatory element) family: structures which regulate mRNA translation or stability.
Theil, E. C. (1993) · PubMed · Cited by 57
Iron Prevents Ferritin Turnover in Hepatic Cells
Truty, J., Malpe, R., & Linder, M. C. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m105392200 · Cited by 49
Conditional Derepression of Ferritin Synthesis in Cells Expressing a Constitutive IRP1 Mutant
Wang, J., & Pantopoulos, K. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.13.4638-4651.2002 · Cited by 49
Kakhlon, O., Gruenbaum, Y., & Cabantchik, Z. I. (2002) · Biochemical Journal · doi:10.1042/0264-6021:3630431 · Cited by 44
Cremonesi, L., Cozzi, A., Girelli, D., Ferrari, F., Fermo, I., Foglieni, B., Levi, S., Bozzini, C., Camparini, M., Ferrari, M., et al. (2004) · Journal of Medical Genetics · doi:10.1136/jmg.2003.011718 · Cited by 43
Self-citationTransient overexpression of human H- and L-ferritin chains in COS cells
Corsi, B., Perrone, F., Bourgeois, M., Beaumont, C., Panzeri, M. C., Cozzi, A., Sangregorio, R., Santambrogio, P., Albertini, A., Arosio, P., et al. (1998) · Biochemical Journal · doi:10.1042/bj3300315 · Cited by 42
Self-citationRepression of the heavy ferritin chain increases the labile iron pool of human K562 cells
Kakhlon, O., Gruenbaum, Y., & Cabantchik, Z. I. (2001) · Biochemical Journal · doi:10.1042/bj3560311 · Cited by 37
Cozzi, A., Levi, S., Bazzigaluppi, E., Ruggeri, G., & Arosio, P. (1989) · Clinica Chimica Acta · doi:10.1016/0009-8981(89)90052-1 · Cited by 34
Self-citationModel for intermediate steps in monocytic differentiation: c-myc, c-fms, and ferritin as markers.
Cayre, Y. E., Raynal, M. C., Darżynkiewicz, Z., & Dörner, M. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.21.7619 · Cited by 33
Kakhlon, O., Gruenbaum, Y., & Cabantchik, Z. I. (2002) · Biochemical Journal · doi:10.1042/bj3630431 · Cited by 30
Kikyo, N., Masahiro, S. U. D. A., Kikyo, N., Hagiwara, K., Yasukawa, K., Fujisawa, M., Yazaki, Y., & Okabe, T. (1994) · PubMed · Cited by 19
Ruggeri, G., Santambrogio, P., Bonfiglio, F., Levi, S., Bugari, G., Verardi, R., Cazzola, M., Invernizzi, R., Zambell, L. M., Albertini, A., et al. (1992) · British Journal of Haematology · doi:10.1111/j.1365-2141.1992.tb08183.x · Cited by 13
Self-citationStimulation of growth of neuroblastoma cells by ferritin in vitro.
Blatt, J., & Wharton, V. (1992) · PubMed · Cited by 10
Cited by
Sorted by citations
Iron and cancer: more ore to be mined
Torti, S. V., & Torti, F. M. (2013) · Nature Reviews Cancer · doi:10.1038/nrc3495 · Cited by 1,621
Ferritins: A family of molecules for iron storage, antioxidation and more
Arosio, P., Ingrassia, R., & Cavadini, P. (2009) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2008.09.004 · Cited by 886
Self-citationPham, C. G., Bubici, C., Zazzeroni, F., Papa, S., Jones, J., Alvarez, K., Jayawardena, S., De Smaele, E., Cong, R., Beaumont, C., et al. (2004) · Cell · doi:10.1016/j.cell.2004.10.017 · Cited by 663
Mechanisms of mammalian iron homeostasis
Pantopoulos, K., Porwal, S. K., Tartakoff, A., & Devireddy, L. (2012) · Biochemistry · doi:10.1021/bi300752r · Cited by 598
Intracellular 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
“Indeed, over-expression or knockdown of ferritin expression in mammalian cells has proven the cytoprotective role of ferritin under proox-idative conditions (59, 60, 78, 159, 227, 243).”
Metadata
- Authors
- Cozzi, A., Corsi, B., Levi, S., Santambrogio, P., Biasiotto, G., & Arosio, P.
- Affiliations
- IRCCS San Raffaele Roma (IT)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2004-03-15
- Volume
- 103
- Issue
- 6
- Pages
- 2377-2383
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W1519013154
- Cited by
- 132
- References
- 43
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 7 · 2022: 3 · 2021: 2 · 2020: 6 · 2019: 5 · 2018: 1 · 2017: 3 · 2016: 4 · 2015: 7 · 2014: 9 · 2013: 21 · 2012: 4
- FWCI
- 3.07
- Type
- journal article
- Language
- en
- Open access
- Licence
- other-oa
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Ferroptosis and cancer prognosis
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- H-ferritin, L-ferritin, HeLa cells, cell proliferation, iron homeostasis, iron availability, iron supplementation, chelation, siRNA knockdown
- MeSH terms
- Quaternary Ammonium Compounds, Buffers, Cell Division, Ferric Compounds, Ferritins, HeLa Cells, Humans, Iron, Transfection, Down-Regulation, Up-Regulation, Gene Expression, DNA, Complementary, Oxidative Stress, RNA, Small Interfering
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