Sustained Hydrogen Peroxide Induces Iron Uptake by Transferrin Receptor-1 Independent of the Iron Regulatory Protein/Iron-responsive Element Network
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Local and systemic inflammatory conditions are characterized by the intracellular deposition of excess iron, which may promote tissue damage via Fenton chemistry. Because the Fenton reactant H(2)O(2) is continuously released by inflammatory cells, a tight regulation of iron homeostasis is required. Here, we show that exposure of cultured cells to sustained low levels of H(2)O(2) that mimic its release by inflammatory cells leads to up-regulation of transferrin receptor 1 (TfR1), the major iron uptake protein. The increase in TfR1 results in increased transferrin-mediated iron uptake and cellular accumulation of the metal. Although iron regulatory protein 1 is transiently activated by H(2)O(2), this response is not sufficient to stabilize TfR1 mRNA and to repress the synthesis of the iron storage protein ferritin. The induction of TfR1 is also independent of transcriptional activation via hypoxia-inducible factor 1alpha or significant protein stabilization. In contrast, pulse experiments with (35)S-labeled methionine/cysteine revealed an increased rate of TfR1 synthesis in cells exposed to sustained low H(2)O(2) levels. Our results suggest a novel mechanism of iron accumulation by sustained H(2)O(2), based on the translational activation of TfR1, which could provide an important (patho) physiological link between iron metabolism and inflammation.
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Low levels of H2O2 increase TfR1 expression.
“Recently, low levels of H2O2 were shown to increase TfR1 expression (8).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [8]
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Chen‐Roetling, J., Liu, W., & Regan, R. F. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.08.021 · Cited by 13 · see citing works
Increased iron in HCV infection: Collateral damage or antiviral defense?
Mueller, S. (2010) · Journal of Hepatology · doi:10.1016/j.jhep.2010.08.003 · Cited by 9 · see citing works
Self-citationSikorska, K., Romanowski, T., & Bielawski, K. P. (2014) · Biotechnologia · doi:10.5114/bta.2011.46517 · Cited by 8 · see citing works
Rahman, M. A., Amirkhani, A., Mempin, M., Ahn, S. B., Deva, A. K., Baker, M. S., Vickery, K., & Hu, H. (2024) · Proteomes · doi:10.3390/proteomes12030022 · Cited by 6 · see citing works
Padovani, D., & Galardon, E. (2022) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.1c00313 · Cited by 6 · see citing works
Physicians' practices regarding management of antituberculosis drug-induced hepatotoxicity.
Thongraung, W., Lertphongpiroon, W., Pungrassami, P., & Ratanajamit, C. (2012) · PubMed · Cited by 3 · see citing works
Mueller, S., Mueller, J. H., Li, S., Zheng, C., & Chen, C. (2023) · Springer eBooks · doi:10.1007/978-3-031-32483-3_57 · Cited by 2 · see citing works
Self-citationThe Role of Oxidative Stress in Hepatocarcinogenesis
Seitz, H. K., & Mueller, S. (2015) · Oxidative stress in applied basic research and clinical practice · doi:10.1007/978-3-319-15539-5_21 · Cited by 1 · see citing works
Self-citationThe role of iron in rheumatoid arthritis
Al-Qenaei, A. (2008) · The University of Bath Online Publications Store (The University of Bath)
- Authors
- Andriopoulos, B., Hegedüsch, S., Mangin, J., Riedel, H.-D., Hebling, U., Wang, J., Pantopoulos, K., & Mueller, S.
- Affiliations
- Heidelberg University (DE)
- Jewish General Hospital (CA)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Mueller, Sebastian
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2007-07
- Volume
- 282
- Issue
- 28
- Pages
- 20301-20308
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2086246137
- Cited by
- 48
- References
- 61
- Citations by year
- 2024: 3 · 2023: 3 · 2022: 2 · 2018: 3 · 2017: 2 · 2016: 1 · 2015: 2 · 2014: 2 · 2013: 4 · 2012: 2
- FWCI
- 3.62
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- hydrogen peroxide, transferrin receptor 1, iron absorption, iron homeostasis, iron regulatory protein 1, iron-responsive element, inflammation, ferritin, Fenton reaction, translational activation, hypoxia-inducible factor-1α, protein synthesis
- MeSH terms
- Ferritins, HeLa Cells, Homeostasis, Humans, Hydrogen Peroxide, Inflammation, Iron, Receptors, Transferrin, Transferrin, Protein Biosynthesis, Transcriptional Activation, Antigens, CD, Up-Regulation, Response Elements, Iron-Regulatory Proteins
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