ArticleProceedings of the National Academy of Sciences of the United States of America2004
Targeted disruption of Nrf2 causes regenerative immune-mediated hemolytic anemia.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 121 citations in OpenAlex.
- Non-canonical roles of Keap1/Nrf2 in regulating quiescence and early activation in adult muscle stem cells.Nature communications · 2025Article
- Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases.Redox biology · 2025Review
- Nrf2 Regulates Basal Glutathione Production in Astrocytes.International journal of molecular sciences · 2025Article
- Depletion of miR-144/451 alleviates anemia in β-thalassemic mice.Blood advances · 2024Article
- Nrf2 Plays a Key Role in Erythropoiesis during Aging.Antioxidants (Basel, Switzerland) · 2024Article
- Iron overload induces dysplastic erythropoiesis and features of myelodysplasia in Nrf2-deficient mice.Leukemia · 2024Article
- Iron chelation improves ineffective erythropoiesis and iron overload in myelodysplastic syndrome mice.eLife · 2023Article
- The SWI/SNF chromatin-remodeling subunit DPF2 facilitates NRF2-dependent antiinflammatory and antioxidant gene expression.The Journal of clinical investigation · 2023Article
- Crosstalk betweenGenes · 2023Article
- NRF2 and the Moirai: Life and Death Decisions on Cell Fates.Antioxidants & redox signaling · 2023Review
- Review
- Immunoglobulin G and phosphatidylserine in regenerative and nonregenerative immune-mediated anemias of dogs.Journal of veterinary internal medicine · 2021Article
- Pleckstrin-2 is essential for erythropoiesis in β-thalassemic mice, reducing apoptosis and enhancing enucleation.Communications biology · 2021Article
- Elevated type I interferon responses potentiate metabolic dysfunction, inflammation, and accelerated aging in mtDNA mutator mice.Science advances · 2021Article
- Deficiency of Antioxidative Paraoxonase 2 (Pon2) Leads to Increased Number of Phenotypic LT-HSCs and Disturbed Erythropoiesis.Oxidative medicine and cellular longevity · 2021Article
- High NRF2 Levels Correlate with Poor Prognosis in Colorectal Cancer Patients and with Sensitivity to the Kinase Inhibitor AT9283 In Vitro.Biomolecules · 2020Article
- Cardamonin Inhibits Oxazolone-Induced Atopic Dermatitis by the Induction of NRF2 and the Inhibition of Th2 Cytokine Production.Antioxidants (Basel, Switzerland) · 2020Article
- NRF2 mediates γ-globin gene regulation through epigenetic modifications in a β-YAC transgenic mouse model.Experimental biology and medicine (Maywood, N.J.) · 2020Article
- Nrf2 deficiency in mice attenuates erythropoietic stress-related macrophage hypercellularity.Experimental hematology · 2020Article
- Chronic arsenic exposure induces the time-dependent modulation of inflammation and immunosuppression in spleen.Cell & bioscience · 2020Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
A basic leucine zipper transcription factor, NF-E2-related factor 2 (Nrf2), plays a critical role in the cellular defense mechanism by mediating a coordinate up-regulation of antioxidant responsive element-driven detoxification and antioxidant genes. Here, we report that targeted disruption of Nrf2 causes regenerative immune-mediated hemolytic anemia due to increased sequestration of damaged erythrocytes. Splenomegaly and spleen toxicity in Nrf2(-/-) mice raised a possibility of hemolytic anemia and splenic extramedullary hematopoiesis in Nrf2(-/-) mice. In support of this, hematology analysis revealed that Nrf2(-/-) mice suffer from anemia with abnormal red cell morphologies (i.e., Howell-Jolly bodies, acantocytes, and schistocytes). In addition, Nrf2(-/-) erythrocytes were more sensitive to H(2)O(2)-induced hemolysis, and erythrocyte-bound IgG levels were markedly increased in Nrf2(-/-) mice compared with Nrf2(+/+) mice. Because IgG bound to erythrocytes in the presence of oxidative damage in erythrocytes (regardless of Nrf2 genotype), these data support that Nrf2(-/-) erythrocytes have higher levels of damage compared with Nrf2(+/+) cells. Finally, Nrf2(-/-) mice showed increased levels of erythrocyte-bound IgG compared with Nrf2(+/+) mice after H(2)O(2) injection in vivo, suggesting that the decreased glutathione and increased H(2)O(2) render the Nrf2(-/-) mice more susceptible to toxicity. Taken together, these observations indicate that a chronic increase in oxidative stress due to decreased antioxidant capacity sensitizes erythrocytes and causes hemolytic anemia in Nrf2(-/-) mice, suggesting a pivotal role of Nrf2-antioxidant responsive element pathway in the cellular antioxidant defense system.
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Registered trials
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