ArticleFree radical biology & medicine2006
A new paradigm: manganese superoxide dismutase influences the production of H2O2 in cells and thereby their biological state.
Article in Free radical biology & medicine, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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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.
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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.
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Who cites it
84 citing papers in PubMed, 198 citations in OpenAlex.
- Phase IIb, Randomized, Double-Blind Trial of GC4419 Versus Placebo to Reduce Severe Oral Mucositis Due to Concurrent Radiotherapy and Cisplatin For Head and Neck Cancer.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2019Trial
- Phase 1b/2a Trial of the Superoxide Dismutase Mimetic GC4419 to Reduce Chemoradiotherapy-Induced Oral Mucositis in Patients With Oral Cavity or Oropharyngeal Carcinoma.International journal of radiation oncology, biology, physics · 2018Trial
- Modulation of detoxification enzymes by watercress: in vitro and in vivo investigations in human peripheral blood cells.European journal of nutrition · 2009Trial
- Manganese Superoxide Dismutase: Structure, Function, and Implications in Human Disease.Antioxidants (Basel, Switzerland) · 2025Review
- Association of Tramadol-Induced Ovarian Damage and Reproductive Dysfunction with Adenosine Triphosphate and the Protective Role of Exogenous ATP Treatment.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Does each Component of Reactive Oxygen Species have a Dual Role in the Tumor Microenvironment?Current medicinal chemistry · 2024Review
- Article
- Immunomodulatory activity of manganese dioxide nanoparticles: Promising for novel vaccines and immunotherapeutics.Frontiers in immunology · 2023Review
- Metabolic Features of Brain Function with Relevance to Clinical Features of Alzheimer and Parkinson Diseases.Molecules (Basel, Switzerland) · 2022Review
- Mechanisms of manganese-induced neurotoxicity and the pursuit of neurotherapeutic strategies.Frontiers in pharmacology · 2022Review
- Targeting oxidative stress in disease: promise and limitations of antioxidant therapy.Nature reviews. Drug discovery · 2021Review
- Protective roles of thymoquinone and vildagliptin in manganese-induced nephrotoxicity in adult albino rats.Environmental science and pollution research international · 2021Article
- Avasopasem manganese synergizes with hypofractionated radiation to ablate tumors through the generation of hydrogen peroxide.Science translational medicine · 2021Article
- Intersections Between Mitochondrial Metabolism and Redox Biology Mediate Posttraumatic Osteoarthritis.Current rheumatology reports · 2021Review
- HMedical oncology (Northwood, London, England) · 2021Article
- Endogenous HMaterials (Basel, Switzerland) · 2021Article
- Evaluation of the redox state in mouse organs following radon inhalation.Journal of radiation research · 2021Article
- "Metal elements and pesticides as risk factors for Parkinson's disease - A review".Toxicology reports · 2021Review
- The immunohistochemical and histologic effects of contrast medium on uterus, fallopian tubes and ovaries, given during hysterosalpingography: rat studyJournal of the Turkish German Gynecological Association · 2020Article
- Exposure to Static Magnetic and Electric Fields Treats Type 2 Diabetes.Cell metabolism · 2020Article
24 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The principal source of hydrogen peroxide in mitochondria is thought to be from the dismutation of superoxide via the enzyme manganese superoxide dismutase (MnSOD). However, the nature of the effect of SOD on the cellular production of H(2)O(2) is not widely appreciated. The current paradigm is that the presence of SOD results in a lower level of H(2)O(2) because it would prevent the non-enzymatic reactions of superoxide that form H(2)O(2). The goal of this work was to: a) demonstrate that SOD can increase the flux of H(2)O(2), and b) use kinetic modelling to determine what kinetic and thermodynamic conditions result in SOD increasing the flux of H(2)O(2). We examined two biological sources of superoxide production (xanthine oxidase and coenzyme Q semiquinone, CoQ(*-) that have different thermodynamic and kinetic properties. We found that SOD could change the rate of formation of H(2)O(2) in cases where equilibrium-specific reactions form superoxide with an equilibrium constant (K) less than 1. An example is the formation of superoxide in the electron transport chain (ETC) of the mitochondria by the reaction of ubisemiquinone radical with dioxygen. We measured the rate of release of H(2)O(2) into culture medium from cells with differing levels of MnSOD. We found that the higher the level of SOD, the greater the rate of accumulation of H(2)O(2). Results with kinetic modelling were consistent with this observation; the steady-state level of H(2)O(2) increases if K<1, for example CoQ(*-)+O(2)-->CoQ+O(2)(*-). However, when K>1, e.g. xanthine oxidase forming O(2)(*-), SOD does not affect the steady state-level of H(2)O(2). Thus, the current paradigm that SOD will lower the flux of H(2)O(2) does not hold for the ETC. These observations indicate that MnSOD contributes to the flux of H(2)O(2) in cells and thereby is involved in establishing the cellular redox environment and thus the biological state of the cell.
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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.