ArticleBlood2013
Erythrocyte NADPH oxidase activity modulated by Rac GTPases, PKC, and plasma cytokines contributes to oxidative stress in sickle cell disease.
Article in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 117 papers, 2 of them syntheses that pooled it.
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
117 citing papers in PubMed, 2 syntheses or guidelines pooled it, 203 citations in OpenAlex.
- Pooled it
- Cardiomyopathy With Restrictive Physiology in Sickle Cell Disease.JACC. Cardiovascular imaging · 2016Pooled it
- Association Between Nitric Oxide, Oxidative Stress, Eryptosis, Red Blood Cell Microparticles, and Vascular Function in Sickle Cell Anemia.Frontiers in immunology · 2020Trial
- High titres of IgM-bound circulating immune complexes and erythrocytic oxidative damage are indicators of dengue severity.Clinical and experimental immunology · 2019Trial
- Antibody-Dependent and Antibody-Independent Hemolysis in Sickle Cell Disease.Antibodies (Basel, Switzerland) · 2026Review
- Reactive Oxygen Species in Cardiovascular and Hematological Diseases: Mechanisms and Therapeutic Strategies.Cureus · 2026Review
- Curcumin's Protective Effects Against HMolecules (Basel, Switzerland) · 2026Review
- Angiotensin signaling is essential for stress erythropoiesis but causes retention of dysfunctional mitochondria in RBCs.JCI insight · 2026Article
- Elevated tricuspid regurgitation velocity in adults with sickle cell disease and HbAA controls in Kinshasa, Democratic Republic of the Congo: a comparative cross-sectional study.Annals of hematology · 2026Article
- A novel transdermal curcumin gel shows potential in improving cardiac bioenergetic functions in Berkeley sickle cell mice.Blood vessels, thrombosis & hemostasis · 2026Article
- The diabetic retina-brain axis hypothesis in diabetic cognitive impairment: from pathophysiological mechanisms to therapeutic implications.Frontiers in endocrinology · 2026Review
- MeMAGEN: A Phase IIa/IIb open-label trial of memantine testing safety and tolerability in sickle cell patients.HemaSphere · 2026Article
- Redox Regulation of Complement Pathway Activation in Aging and Related Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- Redefining the concept of erythrocyte senescence: is eryptosis fundamentally different from erythrocyte senescence.GeroScience · 2025Review
- Inhibition of Galectin-3 by ADSC-derived exosomes after cavernous nerve injury ameliorates erectile dysfunction by modulating oxidative stress and inflammatory profibrotic cascades.Stem cell research & therapy · 2025Article
- Redox Homeostasis in Red Blood Cells: From Molecular Mechanisms to Antioxidant Strategies.Current issues in molecular biology · 2025Review
- Article
- Current understanding of eryptosis: mechanisms, physiological functions, role in disease, pharmacological applications, and nomenclature recommendations.Cell death & disease · 2025Review
- NADPH oxidases: redox regulation of cell homeostasis and disease.Physiological reviews · 2025Review
- Crosstalk Between Sickle Cell Disease and Ferroptosis.International journal of molecular sciences · 2025Review
57 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
Chronic inflammation has emerged as an important pathogenic mechanism in sickle cell disease (SCD). One component of this inflammatory response is oxidant stress mediated by reactive oxygen species (ROS) generated by leukocytes, endothelial cells, plasma enzymes, and sickle red blood cells (RBC). Sickle RBC ROS generation has been attributed to sickle hemoglobin auto-oxidation and Fenton chemistry reactions catalyzed by denatured heme moieties bound to the RBC membrane. In this study, we demonstrate that a significant part of ROS production in sickle cells is mediated enzymatically by NADPH oxidase, which is regulated by protein kinase C, Rac GTPase, and intracellular Ca(2+) signaling within the sickle RBC. Moreover, plasma from patients with SCD and isolated cytokines, such as transforming growth factor β1 and endothelin-1, enhance RBC NADPH oxidase activity and increase ROS generation. ROS-mediated damage to RBC membrane components is known to contribute to erythrocyte rigidity and fragility in SCD. Erythrocyte ROS generation, hemolysis, vaso-occlusion, and the inflammatory response to tissue damage may therefore act in a positive-feedback loop to drive the pathophysiology of sickle cell disease. These findings suggest a novel pathogenic mechanism in SCD and may offer new therapeutic targets to counteract inflammation and RBC rigidity and fragility in SCD.
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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.