ArticleFree radical biology & medicine2010
Ascorbate protects endothelial barrier function during septic insult: Role of protein phosphatase type 2A.
Article in Free radical biology & medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03422159 (Outcomes of Metabolic Resuscitation Using Ascorbic Acid, Thiamine, and Glucocorticoids in the Early Treatment of Sepsis.), which is not on this map. Cited by 29 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.
Outcomes of Metabolic Resuscitation Using Ascorbic Acid, Thiamine, and Glucocorticoids in the Early Treatment of Sepsis.
Who cites it
29 citing papers in PubMed, 65 citations in OpenAlex.
- Effect of Intravenous Injection of Vitamin C on Postoperative Pulmonary Complications in Patients Undergoing Cardiac Surgery: A Double-Blind, Randomized Trial.Drug design, development and therapy · 2020Trial
- Sodium ascorbate versus ascorbic acid in sepsis: a narrative review of emerging cardiovascular and neurological benefits.Critical care (London, England) · 2026Review
- Vitamin C as a treatment for organ failure in sepsis.European journal of medical research · 2023Review
- Enhanced Antioxidant Effects of the Anti-Inflammatory Compound Probucol When Released from Mesoporous Silica Particles.Pharmaceutics · 2022Article
- A Cecal Slurry Mouse Model of Sepsis Leads to Acute Consumption of Vitamin C in the Brain.Nutrients · 2020Article
- Vasoplegic syndrome following cardiothoracic surgery-review of pathophysiology and update of treatment options.Critical care (London, England) · 2020Review
- Angiotensin II Decreases Endothelial Nitric Oxide Synthase PhosphorylationFrontiers in physiology · 2020Article
- Structure, Function, and Regulation of the Blood-Brain Barrier Tight Junction in Central Nervous System Disorders.Frontiers in physiology · 2020Review
- Influence of Vitamin C on Antioxidant Capacity of In Vitro Perfused Porcine Kidneys.Nutrients · 2019Article
- Article
- Vitamin C alone does not improve treatment outcomes in mechanically ventilated patients with severe sepsis or septic shock: a retrospective cohort study.Journal of thoracic disease · 2019Article
- Hydrocortisone, Vitamin C and thiamine for the treatment of sepsis and septic shock following cardiac surgery.Indian journal of anaesthesia · 2018Article
- Vitamin C in the critically ill - indications and controversies.World journal of critical care medicine · 2018Review
- Vitamin C to Improve Organ Dysfunction in Cardiac Surgery Patients-Review and Pragmatic Approach.Nutrients · 2018Review
- The association between tidal volume and neurological outcome following in-hospital cardiac arrest.Resuscitation · 2018Observational
- Dual Functioned Pegylated Phospholipid Micelles Containing Cationic Antimicrobial Decapeptide for Treating Sepsis.Theranostics · 2017Article
- Methylphenidate-triggered ROS generation promotes caveolae-mediated transcytosis via Rac1 signaling and c-Src-dependent caveolin-1 phosphorylation in human brain endothelial cells.Cellular and molecular life sciences : CMLS · 2016Article
- Blocking protein phosphatase 2A signaling prevents endothelial-to-mesenchymal transition and renal fibrosis: a peptide-based drug therapy.Scientific reports · 2016Article
- Lipid rafts regulate PCB153-induced disruption of occludin and brain endothelial barrier function through protein phosphatase 2A and matrix metalloproteinase-2.Toxicology and applied pharmacology · 2015Article
- Roles of Serine/Threonine Phosphatases in Low-Dose Endothelial Monocyte-Activating Polypeptide-II-Induced Opening of Blood-Tumor Barrier.Journal of molecular neuroscience : MN · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
Endothelial barrier dysfunction contributes to morbidity in sepsis. We tested the hypothesis that raising the intracellular ascorbate concentration protects the endothelial barrier from septic insult by inhibiting protein phosphatase type 2A. Monolayer cultures of microvascular endothelial cells were incubated with ascorbate, dehydroascorbic acid (DHAA), the NADPH oxidase inhibitors apocynin and diphenyliodonium, or the PP2A inhibitor okadaic acid and then were exposed to septic insult (lipopolysaccharide and interferon-gamma). Under standard culture conditions that depleted intracellular ascorbate, septic insult stimulated oxidant production and PP2A activity, dephosphorylated phosphoserine and phosphothreonine residues in the tight junction-associated protein occludin, decreased the abundance of occludin at cell borders, and increased monolayer permeability to albumin. NADPH oxidase inhibitors prevented PP2A activation and monolayer leak, showing that these changes required reactive oxygen species. Okadaic acid, at a concentration that inhibited PP2A activity and monolayer leak, prevented occludin dephosphorylation and redistribution, implicating PP2A in the response of occludin to septic insult. Incubation with ascorbate or DHAA raised intracellular ascorbate concentrations and mitigated the effects of septic insult. In conclusion, ascorbate acts within microvascular endothelial cells to inhibit septic stimulation of oxidant production by NADPH oxidase and thereby prevents PP2A activation, PP2A-dependent dephosphorylation and redistribution of occludin, and disruption of the endothelial barrier.
Indexed as
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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.