ArticleBlood2011
Vitamin C is dispensable for oxygen sensing in vivo.
Article in Blood, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 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
42 citing papers in PubMed, 76 citations in OpenAlex.
- Metabolomics-driven elucidation of the synergistic therapeutic mechanism of a novel SGLT-2/PPAR-γ dual receptor supramolecular system for treatment diabetes and obesity.Journal of pharmaceutical analysis · 2025Article
- Maternal Vitamin C Deficiency and Genetic Risk Factors Contribute to Congenital Defects through Dysregulation of DNA Methylation.bioRxiv : the preprint server for biology · 2025Article
- MicroRNA-210 Enhances Cell Survival and Paracrine Potential for Cardiac Cell Therapy While Targeting Mitophagy.Journal of functional biomaterials · 2025Article
- Mechanisms of Vitamins Inhibiting Ferroptosis.Antioxidants (Basel, Switzerland) · 2024Review
- Linear ubiquitination regulates the KSHV replication and transcription activator protein to control infection.Nature communications · 2024Article
- Vitamin C: From nutrition to oxygen sensing and epigenetics.Redox biology · 2023Article
- Article
- Ascorbate Is a Primary Antioxidant in Mammals.Molecules (Basel, Switzerland) · 2022Review
- Fount, fate, features, and function of renal erythropoietin-producing cells.Pflugers Archiv : European journal of physiology · 2022Review
- High-Dose Vitamin C Supplementation as a Legitimate Anti-SARS-CoV-2 Prophylaxis in Healthy Subjects-Yes or No?Nutrients · 2022Review
- The regulation of Hypoxia-Inducible Factor-1 (HIF-1alpha) expression by Protein Disulfide Isomerase (PDI).PloS one · 2021Article
- 2-Oxoglutarate-dependent dioxygenases in cancer.Nature reviews. Cancer · 2020Review
- Roles of vitamins in stem cells.Cellular and molecular life sciences : CMLS · 2020Review
- The Emerging Role of Vitamin C as a Treatment for Sepsis.Nutrients · 2020Review
- Mechanisms of hypoxia signalling: new implications for nephrology.Nature reviews. Nephrology · 2019Review
- Vitamin C and immune cell function in inflammation and cancer.Biochemical Society transactions · 2018Review
- Ascorbic acid metabolism and functions: A comparison of plants and mammals.Free radical biology & medicine · 2018Review
- Metabolic zonation of the liver: The oxygen gradient revisited.Redox biology · 2017Review
- Oxygen availability and metabolic adaptations.Nature reviews. Cancer · 2016Review
- Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Prolyl-4-hydroxylation is necessary for proper structural assembly of collagens and oxygen-dependent protein stability of hypoxia-inducible transcription factors (HIFs). In vitro function of HIF prolyl-4-hydroxylase domain (PHD) enzymes requires oxygen and 2-oxoglutarate as cosubstrates with iron(II) and vitamin C serving as cofactors. Although vitamin C deficiency is known to cause the collagen-disassembly disease scurvy, it is unclear whether cellular oxygen sensing is similarly affected. Here, we report that vitamin C-deprived Gulo(-/-) knockout mice show normal HIF-dependent gene expression. The systemic response of Gulo(-/-) animals to inspiratory hypoxia, as measured by plasma erythropoietin levels, was similar to that of animals supplemented with vitamin C. Hypoxic HIF induction was also essentially normal under serum- and vitamin C-free cell-culture conditions, suggesting that vitamin C is not required for oxygen sensing in vivo. Glutathione was found to fully substitute for vitamin C requirement of all 3 PHD isoforms in vitro. Consistently, glutathione also reduced HIF-1α protein levels, transactivation activity, and endogenous target gene expression in cells exposed to CoCl(2). A Cys201Ser mutation in PHD2 increased basal hydroxylation rates and conferred resistance to oxidative damage in vitro, suggesting that this surface-accessible PHD2 cysteine residue is a target of antioxidative protection by vitamin C and glutathione.
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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.