ArticleFree radical biology & medicine2012
Ascorbate stimulates endothelial nitric oxide synthase enzyme activity by rapid modulation of its phosphorylation status.
Article in Free radical biology & medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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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.
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.
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Who cites it
31 citing papers in PubMed, 52 citations in OpenAlex.
- Intravenous megadose sodium ascorbate normalises elevations in intracranial pressure and restores pressor responsiveness to norepinephrine in ovine Gram-negative sepsis.Scientific reports · 2026Article
- Beetroot Plus Vitamin C for Performance and Recovery: Protocol of a Double-Blind, Placebo-Controlled, Randomized Crossover Trial in Semi-Professional Wrestlers.Health science reports · 2026Article
- Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations.International journal of molecular sciences · 2026Review
- Ascorbate elastomer-coated ePTFE grafts inhibit neointimal hyperplasia and enhance vascular healing.Bioactive materials · 2026Article
- Sodium ascorbate versus ascorbic acid in sepsis: a narrative review of emerging cardiovascular and neurological benefits.Critical care (London, England) · 2026Review
- The Role of Micronutrients in Atherosclerosis: Mechanisms and Clinical Application.Journal of cellular and molecular medicine · 2025Review
- Early, very high-dose, and prolonged vitamin C administration in murine sepsis.Scientific reports · 2025Article
- Replicative Endothelial Cell Senescence May Lead to Endothelial Dysfunction by Increasing the BH2/BH4 Ratio Induced by Oxidative Stress, Reducing BH4 Availability, and Decreasing the Expression of eNOS.International journal of molecular sciences · 2024Article
- Ascorbic Acid vs Calcitriol in Influencing Monocyte Chemoattractant Protein-1, Nitric Oxide, Superoxide Dismutase, as Markers of Endothelial Dysfunction: In Vivo Study in Atherosclerosis Rat Model.Vascular health and risk management · 2023Article
- Nutrition Strategies Promoting Healthy Aging: From Improvement of Cardiovascular and Brain Health to Prevention of Age-Associated Diseases.Nutrients · 2022Review
- Therapeutic potential of megadose vitamin C to reverse organ dysfunction in sepsis and COVID-19.British journal of pharmacology · 2021Review
- Targeting Oxidative Stress in Septic Acute Kidney Injury: From Theory to Practice.Journal of clinical medicine · 2021Review
- Article
- Vitamin C: historical perspectives and heart failure.Heart failure reviews · 2021Review
- Reversal of the Pathophysiological Responses to Gram-Negative Sepsis by Megadose Vitamin C.Critical care medicine · 2021Article
- Vitamin C and Cardiovascular Disease: An Update.Antioxidants (Basel, Switzerland) · 2020Review
- Reactive Species in Huntington Disease: Are They Really the Radicals You Want to Catch?Antioxidants (Basel, Switzerland) · 2020Review
- BRG1 ActivatesFrontiers in cell and developmental biology · 2020Article
- Biochemical basis and metabolic interplay of redox regulation.Redox biology · 2019Review
- Vitamin C, Aging and Alzheimer's Disease.Nutrients · 2017Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Long-term exposure to ascorbate is known to enhance endothelial nitric oxide synthase (eNOS) activity by stabilizing the eNOS cofactor tetrahydrobiopterin (BH4). We investigated acute effects of ascorbate on eNOS function in primary (HUVEC) and immortalized human endothelial cells (EA.hy926), aiming to provide a molecular explanation for the rapid vasodilatation seen in vivo upon administration of ascorbate. Enzymatic activity of eNOS and intracellular BH4 levels were assessed by means of an arginine-citrulline conversion assay and HPLC analysis, respectively. Over a period of 4h, ascorbate steadily increased eNOS activity, although endothelial BH4 levels remained unchanged compared to untreated control cells. Immunoblot analyses revealed that as early as 5 min after treatment ascorbate dose-dependently increased phosphorylation at eNOS-Ser1177 and concomitantly decreased phosphorylation at eNOS-Thr495, a phosphorylation pattern indicative of increased eNOS activity. By employing pharmacological inhibitors, siRNA-mediated knockdown approaches, and overexpression of the catalytic subunit of protein phosphatase 2A (PP2A), we show that this effect was at least partly owing to reduction of PP2A activity and subsequent activation of AMP-activated kinase. In this report, we unravel a novel mechanism for how ascorbate rapidly activates eNOS independent of its effects on BH4 stabilization.
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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.