ArticleThe Journal of clinical investigation2018
Translational repression of HIF2α expression in mice with Chuvash polycythemia reverses polycythemia.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
- Iron‑sulfur clusters in viral proteins: Exploring their elusive nature, roles and new avenues for targeting infections.Biochimica et biophysica acta. Molecular cell research · 2024Review
- An iron-sulfur cluster in the zinc-binding domain of the SARS-CoV-2 helicase modulates its RNA-binding and -unwinding activities.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Insight into SARS-CoV-2 Omicron variant immune escape possibility and variant independent potential therapeutic opportunities.Heliyon · 2023Review
- TEMPOL inhibits SARS-CoV-2 replication and development of lung disease in the Syrian hamster model.iScience · 2022Article
- Article
- Article
- Disruption of cellular iron homeostasis byBrain communications · 2022Article
- Essential role of systemic iron mobilization and redistribution for adaptive thermogenesis through HIF2-α/hepcidin axis.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Review
- Fe-S cofactors in the SARS-CoV-2 RNA-dependent RNA polymerase are potential antiviral targets.Science (New York, N.Y.) · 2021Article
- Mechanisms of cellular iron sensing, regulation of erythropoiesis and mitochondrial iron utilization.Seminars in hematology · 2021Review
- Article
- Iron-responsive-like elements and neurodegenerative ferroptosis.Learning & memory (Cold Spring Harbor, N.Y.) · 2020Review
- Mechanisms of hypoxia signalling: new implications for nephrology.Nature reviews. Nephrology · 2019Review
- NCOA4 maintains murine erythropoiesis via cell autonomous and non-autonomous mechanisms.Haematologica · 2019Article
- The indispensable role of mammalian iron sulfur proteins in function and regulation of multiple diverse metabolic pathways.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2019Review
- New insights into the links between hypoxia and iron homeostasis.Current opinion in hematology · 2019Review
- Hypoxia, angiogenesis, and metabolism in the hereditary kidney cancers.The Journal of clinical investigation · 2019Review
- Hepatic hepcidin/intestinal HIF-2α axis maintains iron absorption during iron deficiency and overload.The Journal of clinical investigation · 2019Article
- Toward a Novel Therapeutic Option for Polycythemia.HemaSphere · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Chuvash polycythemia is an inherited disease caused by a homozygous germline VHLR200W mutation, which leads to impaired degradation of HIF2α, elevated levels of serum erythropoietin, and erythrocytosis/polycythemia. This phenotype is recapitulated by a mouse model bearing a homozygous VhlR200W mutation. We previously showed that iron-regulatory protein 1-knockout (Irp1-knockout) mice developed erythrocytosis/polycythemia through translational derepression of Hif2α, suggesting that IRP1 could be a therapeutic target to treat Chuvash polycythemia. Here, we fed VhlR200W mice supplemented with Tempol, a small, stable nitroxide molecule and observed that Tempol decreased erythropoietin production, corrected splenomegaly, normalized hematocrit levels, and increased the lifespans of these mice. We attribute the reversal of erythrocytosis/polycythemia to translational repression of Hif2α expression by Tempol-mediated increases in the IRE-binding activity of Irp1, as reversal of polycythemia was abrogated in VhlR200W mice in which Irp1 was genetically ablated. Thus, a new approach to the treatment of patients with Chuvash polycythemia may include dietary supplementation of Tempol, which decreased Hif2α expression and markedly reduced life-threatening erythrocytosis/polycythemia in the VhlR200W mice.
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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.