The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
Overexpression of Wild Type and Mutated Human Ferritin H-chain in HeLa Cells
Open accessAbstract
Transfectant HeLa cells were generated that expressed human ferritin H-chain wild type and an H-chain mutant with inactivated ferroxidase activity under the control of the tetracycline-responsive promoter (Tet-off). The clones accumulated exogenous ferritins up to levels 14-16-fold over background, half of which were as H-chain homopolymers. This had no evident effect in the mutant ferritin clone, whereas it induced an iron-deficient phenotype in the H-ferritin wild type clone, manifested by approximately 5-fold increase of IRPs activity, approximately 2.5-fold increase of transferrin receptor, approximately 1.8-fold increase in iron-transferrin iron uptake, and approximately 50% reduction of labile iron pool. Overexpression of the H-ferritin, but not of the mutant ferritin, strongly reduced cell growth and increased resistance to H(2)O(2) toxicity, effects that were reverted by prolonged incubation in iron-supplemented medium. The results show that in HeLa cells H-ferritin regulates the metabolic iron pool with a mechanism dependent on the functionality of the ferroxidase centers, and this affects, in opposite directions, cellular growth and resistance to oxidative damage. This, and the finding that also in vivo H-chain homopolymers are much less efficient than the H/L heteropolymers in taking up iron, indicate that functional activity of H-ferritin in HeLa cells is that predicted from the in vitro data.
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“Accumulating evidence shows that ferritin acts as an antioxidant protein (59, 60, 78, 159, 227, 243).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [60]
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“ferritin H disruption by siRNA sensitized the cells to H2O2-induced oxidative stress (60)”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [60]
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“overexpression or knockdown of ferritin expression in mammalian cells has proven the cytoprotective role of ferritin under prooxidative conditions (59, 60, 78, 159, 227, 243).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [60]
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Metadata
- Authors
- Cozzi, A., Corsi, B., Levi, S., Santambrogio, P., Albertini, A., & Arosio, P.
- Affiliations
- IRCCS Ospedale San Raffaele (IT)
- University of Brescia (IT)
- Corresponding author
- Arosio, Paolo
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2000-08
- Volume
- 275
- Issue
- 33
- Pages
- 25122-25129
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2030928461
- Cited by
- 242
- References
- 36
- Citations by year
- 2025: 4 · 2024: 5 · 2023: 8 · 2022: 4 · 2021: 8 · 2020: 9 · 2019: 7 · 2018: 3 · 2017: 8 · 2016: 7 · 2015: 8 · 2014: 14 · 2013: 9 · 2012: 10
- FWCI
- 6.27
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Ferroptosis and cancer prognosis
- Keywords
- ferroxidase activity, iron metabolism, iron regulatory proteins, transferrin receptor, iron absorption, labile iron pool, oxidative stress resistance, cell growth, HeLa cells, tetracycline-responsive promoter
- MeSH terms
- Anti-Bacterial Agents, Apoferritins, Cell Division, Ceruloplasmin, Doxycycline, Enzyme-Linked Immunosorbent Assay, Ferritins, HeLa Cells, Humans, Hydrogen Peroxide, Iron, Mutation, Plasmids, Precipitin Tests, Promoter Regions, Genetic, Tetracycline, Time Factors, Transfection, Immunoblotting, Mutagenesis, DNA, Complementary, Oxidative Stress
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