ArticleThe Journal of biological chemistry2012
Sustained submicromolar H2O2 levels induce hepcidin via signal transducer and activator of transcription 3 (STAT3).
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 75 citations in OpenAlex.
- The Red Blood Cell-Liver Axis: A New Framework for Iron Homeostasis and Liver Biology.Biology · 2026Article
- Direct Ingestion of Oxidized Red Blood Cells (Efferocytosis) by Hepatocytes.Hepatic medicine : evidence and research · 2024Article
- Iron Status and Supplementation during Tuberculosis.Microorganisms · 2023Review
- Targeting iron metabolism in osteosarcoma.Discover oncology · 2023Review
- Soluble Transferrin Receptor, Antioxidant Status and Cardiometabolic Risk in Apparently Healthy Individuals.Antioxidants (Basel, Switzerland) · 2022Article
- Novel Insights into Alcoholic Liver Disease: Iron Overload, Iron Sensing and Hemolysis.Journal of translational internal medicine · 2022Article
- Resistance Training Attenuates Activation of STAT3 and Muscle Atrophy in Tumor-Bearing Mice.Frontiers in oncology · 2022Article
- Direct modulation of hepatocyte hepcidin signaling by iron.World journal of hepatology · 2021Article
- HRedox biology · 2021Article
- Role of hepcidin in oxidative stress and cell death of cultured mouse renal collecting duct cells: protection against iron and sensitization to cadmium.Archives of toxicology · 2021Article
- NOX1-dependent redox signaling potentiates colonic stem cell proliferation to adapt to the intestinal microbiota by linking EGFR and TLR activation.Cell reports · 2021Article
- Cancer Related Anemia: An Integrated Multitarget Approach and Lifestyle Interventions.Nutrients · 2021Review
- Changes in Hepcidin Levels in an Animal Model of Anemia of Chronic Inflammation: Mechanistic Insights Related to Iron Supplementation and Hepcidin Regulation.Oxidative medicine and cellular longevity · 2021Article
- Omega-3 Fatty Acid and Iron Supplementation Alone, but Not in Combination, Lower Inflammation and Anemia of Infection inNutrients · 2020Article
- Scavenging reactive oxygen species selectively inhibits M2 macrophage polarization and their pro-tumorigenic function in part, via Stat3 suppression.Free radical biology & medicine · 2020Article
- IL-1 beta-mediated macrophage-hepatocyte crosstalk upregulates hepcidin under physiological low oxygen levels.Redox biology · 2019Article
- Could Alzheimer's Disease Originate in the Periphery and If So How So?Molecular neurobiology · 2019Review
- Redox Paradox: A Novel Approach to Therapeutics-Resistant Cancer.Antioxidants & redox signaling · 2018Review
- Hypoxia enhances HRedox biology · 2018Article
- Endogenous hepcidin synthesis protects the distal nephron against hemin and hemoglobin mediated necroptosis.Cell death & disease · 2018Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The peptide hormone hepcidin regulates mammalian iron homeostasis by blocking ferroportin-mediated iron export from macrophages and the duodenum. During inflammation, hepcidin is strongly induced by interleukin 6, eventually leading to the anemia of chronic disease. Here we show that hepatoma cells and primary hepatocytes strongly up-regulate hepcidin when exposed to low concentrations of H(2)O(2) (0.3-6 μM), concentrations that are comparable with levels of H(2)O(2) released by inflammatory cells. In contrast, bolus treatment of H(2)O(2) has no effect at low concentrations and even suppresses hepcidin at concentrations of >50 μM. H(2)O(2) treatment synergistically stimulates hepcidin promoter activity in combination with recombinant interleukin-6 or bone morphogenetic protein-6 and in a manner that requires a functional STAT3-responsive element. The H(2)O(2)-mediated hepcidin induction requires STAT3 phosphorylation and is effectively blocked by siRNA-mediated STAT3 silencing, overexpression of SOCS3 (suppressor of cytokine signaling 3), and antioxidants such as N-acetylcysteine. Glycoprotein 130 (gp130) is required for H(2)O(2) responsiveness, and Janus kinase 1 (JAK1) is required for adequate basal signaling, whereas Janus kinase 2 (JAK2) is dispensable upstream of STAT3. Importantly, hepcidin levels are also increased by intracellular H(2)O(2) released from the respiratory chain in the presence of rotenone or antimycin A. Our results suggest a novel mechanism of hepcidin regulation by nanomolar levels of sustained H(2)O(2). Thus, similar to cytokines, H(2)O(2) provides an important regulatory link between inflammation and iron metabolism.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.