CoChat
Sign Up
Cited by 14Iron Metabolism and DisordersNeurological diseases and metabolismTrace Elements in Health

The DOI matches its Crossref record; the references it cites are not checked yet.

Iron regulatory proteins increase neuronal vulnerability to hydrogen peroxide

Open access
F. Regan, Raymond, Li, Zhi, Chen, Mai, Zhang, Xuefeng, Chen-Roetling, Jing·2008·Biochemical and Biophysical Research Communications
DOI 10.1016/j.bbrc.2008.07.061PMC PMC2556571
Open this paper in CoChat — free account

Abstract

Iron regulatory protein (IRP)-1 and IRP2 inhibit ferritin synthesis by binding to an iron responsive element in the 5'-untranslated region of its mRNA. The present study tested the hypothesis that neurons lacking these proteins would be resistant to hydrogen peroxide (H(2)O(2)) toxicity. Wild-type cortical cultures treated with 100-300microM H(2)O(2) sustained widespread neuronal death, as measured by lactate dehydrogenase assay, and a significant increase in malondialdehyde. Both endpoints were reduced by over 85% in IRP2 knockout cultures. IRP1 gene deletion had a weaker and variable effect, with approximately 20% reduction in cell death at 300microM H(2)O(2). Ferritin expression after H(2)O(2) treatment was increased 1.9- and 6.7-fold in IRP1 and IRP2 knockout cultures, respectively, compared with wild-type. These results suggest that iron regulatory proteins, particularly IRP2, increase neuronal vulnerability to oxidative injury. Therapies targeting IRP2 binding to ferritin mRNA may attenuate neuronal loss due to oxidative stress.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.bbrc.2008.07.061

Cites

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

The citation lists haven’t been fetched yet

References 33 · Cited by 14

Research works printed but not linked: 28

  1. Ke, 2003, Iron misregulation in the brain: a primary cause of neurodegenerative disorders, Lancet Neurol., 2, 246, 10.1016/S1474-4422(03)00353-3 · DOI
  2. Potts, 2006, Traumatic injury to the immature brain: inflammation, oxidative injury, and iron-mediated damage as potential therapeutic targets, NeuroRx, 3, 143, 10.1016/j.nurx.2006.01.006 · DOI · Paper page
  3. Stankiewicz, 2007, Iron in chronic brain disorders: imaging and neurotherapeutic implications, Neurotherapeutics, 4, 371, 10.1016/j.nurt.2007.05.006 · DOI
  4. Arosio, 2002, Ferritin, iron homeostasis, and oxidative damage, Free Radic. Biol. Med., 33, 457, 10.1016/S0891-5849(02)00842-0 · DOI
  5. Panahian, 1999, Overexpression of heme oxygenase-1 is neuroprotective in a model of permanent middle cerebral artery occlusion in transgenic mice, J. Neurochem., 72, 1187, 10.1111/j.1471-4159.1999.721187.x · DOI
  6. Wu, 2003, Iron and iron-handling proteins in the brain after intracerebral hemorrhage, Stroke, 34, 2964, 10.1161/01.STR.0000103140.52838.45 · DOI
  7. Koszyca, 2002, Patterns of immunocytochemical staining for ferritin and transferrin in the human spinal cord following traumatic injury, J. Clin. Neurosci., 9, 298, 10.1054/jocn.2001.0969 · DOI
  8. Faucheux, 2002, Lack of up-regulation of ferritin is associated with sustained iron regulatory protein-1 binding activity in the substantia nigra of patients with Parkinson’s disease, J. Neurochem., 83, 320, 10.1046/j.1471-4159.2002.01118.x · DOI · Paper page
  9. Werner, 2008, Proteome analysis of human substantia nigra in Parkinson’s disease, Proteome Sci., 6, 8, 10.1186/1477-5956-6-8 · DOI
  10. Theil, 2000, Targeting mRNA to regulate iron and oxygen metabolism, Biochem. Pharmacol., 59, 87, 10.1016/S0006-2952(99)00300-7 · DOI
  11. Theil, 2006, Integrating iron and oxygen/antioxidant signals via a combinatorial array of DNA—(antioxidant response elements) and mRNA (iron responsive elements) sequences, J. Inorg. Biochem., 100, 2074, 10.1016/j.jinorgbio.2006.09.011 · DOI
  12. Starke, 1985, Ferric iron and superoxide ions are required for the killing of cultured hepatocytes by hydrogen peroxide. Evidence for the participation of hydroxyl radicals formed by an iron-catalyzed Haber–Weiss reaction, J. Biol. Chem., 260, 10099, 10.1016/S0021-9258(17)39218-9 · DOI
  13. LaVaute, 2001, Targeted deletion of the gene encoding iron regulatory protein-2 causes misregulation of iron metabolism and neurodegenerative disease in mice, Nat. Genet., 27, 209, 10.1038/84859 · DOI · Paper page
  14. Rogers, 2003, Heme oxygenase-2 knockout neurons are less vulnerable to hemoglobin toxicity, Free Radic. Biol. Med., 35, 872, 10.1016/S0891-5849(03)00431-3 · DOI
  15. Koh, 1988, Vulnerability of cultured cortical neurons to damage by excitotoxins: differential susceptibility of neurons containing NADPH-diaphorase, J. Neurosci., 8, 2153, 10.1523/JNEUROSCI.08-06-02153.1988 · DOI
  16. Gwag, 1995, Blockade of glutamate receptors unmasks neuronal apoptosis after oxygen–glucose deprivation in vitro, Neuroscience, 68, 615, 10.1016/0306-4522(95)00232-8 · DOI
  17. Regan, 1993, Neurotoxicity of hemoglobin in cortical cell culture, Neurosci. Lett., 153, 219, 10.1016/0304-3940(93)90326-G · DOI
  18. Meyron-Holtz, 2004, Genetic ablations of iron regulatory proteins 1 and 2 reveal why iron regulatory protein 2 dominates iron homeostasis, EMBO J., 23, 386, 10.1038/sj.emboj.7600041 · DOI · Paper page
  19. Starke, 1985, Lysosomal origin of the ferric iron required for cell killing by hydrogen peroxide, Biochem. Biophys. Res. Commun., 133, 371, 10.1016/0006-291X(85)90916-7 · DOI
  20. Balla, 1992, Ferritin: a cytoprotective stratagem of endothelium, J. Biol. Chem., 267, 18148, 10.1016/S0021-9258(19)37165-0 · DOI
  21. Liddell, 2004, Endogenous glutathione and catalase protect cultured rat astrocytes from the iron-mediated toxicity of hydrogen peroxide, Neurosci. Lett., 364, 164, 10.1016/j.neulet.2004.04.042 · DOI
  22. Tibodeau, 2006, The up-regulation of ferritin expression using a small-molecule ligand to the native mRNA, Proc. Natl. Acad. Sci. USA, 103, 253, 10.1073/pnas.0509744102 · DOI
  23. Festa, 2000, Oxalomalate, a competitive inhibitor of aconitase, modulates the RNA-binding activity of iron-regulatory proteins, Biochem. J., 348, 315, 10.1042/bj3480315 · DOI
  24. Santamaria, 2004, Induction of ferritin expression by oxalomalate, Biochim. Biophys. Acta, 1691, 151, 10.1016/j.bbamcr.2004.01.004 · DOI
  25. Wang, 2007, Excess capacity of the iron regulatory protein system, J. Biol. Chem., 282, 24650, 10.1074/jbc.M703167200 · DOI
  26. Regan, 2008, Neurons lacking iron regulatory protein-2 are highly resistant to the toxicity of hemoglobin, Neurobiol. Dis., 31, 242, 10.1016/j.nbd.2008.04.008 · DOI
  27. Garner, 1997, On the cytoprotective role of ferritin in macrophages and its ability to enhance lysosomal stability, Free Radic. Res., 27, 487, 10.3109/10715769709065788 · DOI
  28. Garner, 1998, Endogenous ferritin protects cells with iron-laden lysosomes against oxidative stress, Free. Radic. Res., 29, 103, 10.1080/10715769800300121 · DOI

Metadata

Authors
F. Regan, R., Li, Z., Chen, M., Zhang, X., & Chen-Roetling, J.
Affiliations
Thomas Jefferson University (US)
ORCID
Venue
Biochemical and Biophysical Research Communications
Publisher
Elsevier BV
Published
2008-10
Volume
375
Issue
1
Pages
6-10
ISSN
0006-291X (ISSN-L)
DOI
10.1016/j.bbrc.2008.07.061
PMC
PMC2556571
OpenAlex
W1995617944
Cited by
14
References
33
Citations by year
2020: 1 · 2017: 2 · 2016: 1 · 2014: 1 · 2012: 2
FWCI
1.52
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Biochemical and Biophysical Research Communications (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • American Heart Association
  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke (NS042273, R01NS042273)
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
iron regulatory protein 1, IRP2, hydrogen peroxide toxicity, oxidative stress, neuronal cell death, ferritin, iron-responsive element, malondialdehyde, cortical neurons, oxidative damage
MeSH terms
Animals, Cells, Cultured, Ferritins, Hydrogen Peroxide, Neurons, Mice, Knockout, Oxidative Stress, Iron Regulatory Protein 1, Iron Regulatory Protein 2, Mice

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

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: Iron regulatory proteins increase neuronal vulnerability to hydrogen peroxide. https://app.cochat.ai/papers/10.1016/j.bbrc.2008.07.061
The paper
F. Regan, R., Li, Z., Chen, M., Zhang, X., & Chen-Roetling, J. (2008). Iron regulatory proteins increase neuronal vulnerability to hydrogen peroxide. Biochemical and Biophysical Research Communications. https://doi.org/10.1016/j.bbrc.2008.07.061