ArticleFree radical biology & medicine2013
Manganese superoxide dismutase depletion in murine hematopoietic stem cells perturbs iron homeostasis, globin switching, and epigenetic control in erythrocyte precursor cells.
Article in Free radical biology & medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 39 citations in OpenAlex.
- Implantable Bioresorbable Scaffold with Fucosylated Chondroitin Sulfate as a Promising Device for Delayed Stimulation of Hematopoiesis.Marine drugs · 2025Article
- A U-Shaped Relationship Between Blood Manganese Levels and Anemia in Patients With CKD: A Cross-Sectional Analysis from National Health and Nutrition Examination Survey 2015 to 2018.Kidney medicine · 2025Article
- Increased Mitochondrial Superoxide Level Is Partially Associated With Vemurafenib-Induced Renal Tubular Toxicity.Basic & clinical pharmacology & toxicology · 2025Article
- A system-level model reveals that transcriptional stochasticity is required for hematopoietic stem cell differentiation.NPJ systems biology and applications · 2024Article
- Effect of Whole Blood Dietary Mineral Concentrations on Erythrocytes: Selenium, Manganese, and Chromium: NHANES Data.Nutrients · 2024Article
- Emerging mitochondrial signaling mechanisms in cardio-oncology: beyond oxidative stress.American journal of physiology. Heart and circulatory physiology · 2022Review
- Mitochondria signaling to the epigenome: A novel role for an old organelle.Free radical biology & medicine · 2021Review
- The epigenetic and morphogenetic effects of molecular oxygen and its derived reactive species in development.Free radical biology & medicine · 2021Article
- An IDH1-vitamin C crosstalk drives human erythroid development by inhibiting pro-oxidant mitochondrial metabolism.Cell reports · 2021Article
- Serum trace metal association with response to erythropoiesis stimulating agents in incident and prevalent hemodialysis patients.Scientific reports · 2020Article
- Succinate Accumulation Links Mitochondrial MnSOD Depletion to Aberrant Nuclear DNA Methylation and Altered Cell Fate.Journal of Experimental Pathology · 2020Article
- Enrichment of superoxide dismutase 2 in glioblastoma confers to acquisition of temozolomide resistance that is associated with tumor-initiating cell subsets.Journal of biomedical science · 2019Article
- Mitochondrial superoxide disrupts the metabolic and epigenetic landscape of CD4Redox biology · 2019Article
- A case-control study of trace-element status and lung cancer in Appalachian Kentucky.PloS one · 2019Article
- Article
- Mouse Models of Erythropoiesis and Associated Diseases.Methods in molecular biology (Clifton, N.J.) · 2018Review
- Excess iron: considerations related to development and early growth.The American journal of clinical nutrition · 2017Review
- On the Origin of Superoxide Dismutase: An Evolutionary Perspective of Superoxide-Mediated Redox Signaling.Antioxidants (Basel, Switzerland) · 2017Review
- Potential role of mitochondrial superoxide decreasing ferrochelatase and heme in coronary artery soluble guanylate cyclase depletion by angiotensin II.American journal of physiology. Heart and circulatory physiology · 2016Article
- Mitochondrial Superoxide Signaling Contributes to Norepinephrine-Mediated T-Lymphocyte Cytokine Profiles.PloS one · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Heme synthesis partially occurs in the mitochondrial matrix; thus there is a high probability that enzymes and intermediates important in the production of heme will be exposed to metabolic by-products including reactive oxygen species. In addition, the need for ferrous iron for heme production, Fe/S coordination, and other processes occurring in the mitochondrial matrix suggests that aberrant fluxes of reactive oxygen species in this compartment might perturb normal iron homeostasis. Manganese superoxide dismutase (Sod2) is an antioxidant enzyme that governs steady-state levels of the superoxide in the mitochondrial matrix. Using hematopoietic stem cell-specific conditional Sod2 knockout mice we observed increased superoxide concentrations in red cell progeny, which caused significant pathologies including impaired erythrocytes and decreased ferrochelatase activity. Animals lacking Sod2 expression in erythroid precursors also displayed extramedullary hematopoiesis and systemic iron redistribution. Additionally, the increase in superoxide flux in erythroid precursors caused abnormal gene regulation of hematopoietic transcription factors, globins, and iron-response genes. Moreover, the erythroid precursors also displayed evidence of global changes in histone posttranslational modifications, a likely cause of at least some of the aberrant gene expression noted. From a therapeutic translational perspective, mitochondrially targeted superoxide-scavenging antioxidants partially rescued the observed phenotype. Taken together, our findings illuminate the superoxide sensitivity of normal iron homeostasis in erythrocyte precursors and suggest a probable link between mitochondrial redox metabolism and epigenetic control of nuclear gene regulation during mammalian erythropoiesis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.