ArticleToxicological sciences : an official journal of the Society of Toxicology2012
Elevated hepatic iron activates NF-E2-related factor 2-regulated pathway in a dietary iron overload mouse model.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 30 citations in OpenAlex.
- Role of Ferroptosis in ALD: Focusing on Hepcidin and Besides Hepcidin.Current medicinal chemistry · 2025Review
- The dual role of autophagy in suppressing and promoting hepatocellular carcinoma.Frontiers in cell and developmental biology · 2024Review
- 6-(7-Nitro-2,1,3-benzoxadiazol-4-ylthio) Hexanol Inhibits Proliferation and Induces Apoptosis of Endometriosis by Regulating Glutathione S-Transferase Mu Class 4.Reproductive sciences (Thousand Oaks, Calif.) · 2023Article
- Supplementation with High or Low Iron Reduces Colitis Severity in an AOM/DSS Mouse Model.Nutrients · 2022Article
- Effects of acute iron overload on Nrf2-related glutathione metabolism in rat brain.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2021Article
- Article
- Nrf2 controls iron homeostasis in haemochromatosis and thalassaemia via Bmp6 and hepcidin.Nature metabolism · 2019Article
- Iron-Induced Liver Injury: A Critical Reappraisal.International journal of molecular sciences · 2019Review
- Comparative Evaluation of U.S. Brand and Generic Intravenous Sodium Ferric Gluconate Complex in Sucrose Injection: Biodistribution after Intravenous Dosing in Rats.Nanomaterials (Basel, Switzerland) · 2017Article
- Spatiotemporal expression and transcriptional regulation of heme oxygenase and biliverdin reductase genes in zebrafish (Danio rerio) suggest novel roles during early developmental periods of heightened oxidative stress.Comparative biochemistry and physiology. Toxicology & pharmacology : CBP · 2017Article
- Characterization of heme oxygenase and biliverdin reductase gene expression in zebrafish (Danio rerio): Basal expression and response to pro-oxidant exposures.Toxicology and applied pharmacology · 2016Article
- Plasma total antioxidant capacity and peroxidation biomarkers in psoriasis.Journal of biomedical science · 2016Review
- Tucum-Do-Cerrado (Bactris setosa Mart.) Consumption Modulates Iron Homeostasis and Prevents Iron-Induced Oxidative Stress in the Rat Liver.Nutrients · 2016Article
- Hyperglycemia mediates a shift from cap-dependent to cap-independent translation via a 4E-BP1-dependent mechanism.Diabetes · 2013Article
- Inhibiting heme oxygenase-1 attenuates rat liver fibrosis by removing iron accumulation.World journal of gastroenterology · 2013Article
- Dietary iron concentration may influence aging process by altering oxidative stress in tissues of adult rats.PloS one · 2013Article
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9 authors at 2 institutions in 2 countries.
Funding
Abstract
Hepatic iron overload has been associated classically with the genetic disorder hereditary hemochromatosis. More recently, it has become apparent that mild-to-moderate degrees of elevated hepatic iron stores observed in other liver diseases also have clinical relevance. The goal was to use a mouse model of dietary hepatic iron overload and isobaric tag for relative and absolute quantitation proteomics to identify, at a global level, differentially expressed proteins in livers from mice fed a control or 3,5,5-trimethyl-hexanoyl-ferrocene (TMHF) supplemented diet for 4 weeks. The expression of 74 proteins was altered by ≥ ±1.5-fold, showing that the effects of iron on the liver proteome were extensive. The top canonical pathway altered by TMHF treatment was the NF-E2-related factor 2 (NRF2-)-mediated oxidative stress response. Because of the long-standing association of elevated hepatic iron with oxidative stress, the remainder of the study was focused on NRF2. TMHF treatment upregulated 25 phase I/II and antioxidant proteins previously categorized as NRF2 target gene products. Immunoblot analyses showed that TMHF treatment increased the levels of glutathione S-transferase (GST) M1, GSTM4, glutamate-cysteine ligase (GCL) catalytic subunit, GCL modifier subunit, glutathione synthetase, glutathione reductase, heme oxygenase 1, epoxide hydrolase 1, and NAD(P)H dehydrogenase quinone 1. Immunofluorescence, carried out to determine the cellular localization of NRF2, showed that NRF2 was detected in the nucleus of hepatocytes from TMHF-treated mice and not from control mice. We conclude that elevated hepatic iron in a mouse model activates NRF2, a key regulator of the cellular response to oxidative stress.
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