ArticleJCI insight2018
Hemoglobin oxidation-dependent reactions promote interactions with band 3 and oxidative changes in sickle cell-derived microparticles.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 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.
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
45 citing papers in PubMed, 68 citations in OpenAlex.
- Trial
- Association Between Nitric Oxide, Oxidative Stress, Eryptosis, Red Blood Cell Microparticles, and Vascular Function in Sickle Cell Anemia.Frontiers in immunology · 2020Trial
- Sickle cell vaso-occlusive episodes correlate with the magnetic heterogeneity of red blood cells.Blood advances · 2026Article
- A novel transdermal curcumin gel shows potential in improving cardiac bioenergetic functions in Berkeley sickle cell mice.Blood vessels, thrombosis & hemostasis · 2026Article
- Urinary Proteomic Signatures in Sickle Cell Disease: Search for Biomarkers Associated With Underlying Molecular Pathways.Advances in hematology · 2026Article
- Breaking the vicious cycle in sickle cell disease: Redox stress impairs red blood cell rheology and promotes lung vasocongestion.Free radical biology & medicine · 2025Article
- Article
- Inflammation and Iron Profile in Children With Sickle Cell Disease in Cameroon: Frequency and Associated Factors, an Analytical Cross-Sectional Study.Health science reports · 2025Article
- Crosstalk Between Sickle Cell Disease and Ferroptosis.International journal of molecular sciences · 2025Review
- The Redox Process in Red Blood Cells: Balancing Oxidants and Antioxidants.Antioxidants (Basel, Switzerland) · 2024Review
- Biopreservation and reversal of oxidative injury during blood storage by a novel curcumin-based gel formulation.Scientific reports · 2024Article
- Biopreservation and Reversal of Oxidative Injury During Blood Storage by a Novel Curcumin-based Gel Formulation.Research square · 2024Article
- Deciphering mTheranostics · 2024Article
- Impact of cold storage on the oxygenation and oxidation reactions of red blood cells.Frontiers in physiology · 2024Article
- Ferroptosis as an emerging target in sickle cell disease.Current research in toxicology · 2024Article
- Erythroid anion transport, nitric oxide, and blood pressure.Frontiers in physiology · 2024Article
- Oxidative Stress in Healthy and Pathological Red Blood Cells.Biomolecules · 2023Review
- Sickle red blood cell-derived extracellular vesicles activate endothelial cells and enhance sickle red cell adhesion mediated by von Willebrand factor.British journal of haematology · 2023Article
- Different-sized extracellular vesicles derived from stored red blood cells package diverse cargoes and cause distinct cellular effects.Transfusion · 2023Article
- Mitochondria: Emerging Consequential in Sickle Cell Disease.Journal of clinical medicine · 2023Review
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
The contribution of intracellular hemoglobin (Hb) oxidation to RBC-derived microparticle (MP) formation is poorly defined in sickle cell disease (SCD). Here we report that sickle Hb (HbS) oxidation, coupled with changes in cytosolic antioxidative proteins, is associated with membrane alterations and MP formation in homozygous Townes-sickle cell (Townes-SS) mice. Photometric and proteomic analyses confirmed the presence of high levels of Hb oxidation intermediates (ferric/ferryl) and consequent β-globin posttranslational modifications, including the irreversible oxidation of βCys93 and the ubiquitination of βLys96 and βLys145. This is the first report to our knowledge to link the UPS (via ubiquitinated Hb and other proteins) to oxidative stress. Ferryl Hb also induced complex formation with band 3 and RBC membrane proteins. Incubation of Townes-SS MPs with human endothelial cells caused greater loss of monolayer integrity, apoptotic activation, heme oxygenase-1 induction, and concomitant bioenergetic imbalance compared with control Townes-AA MPs. MPs obtained from Townes-SS mice treated with hydroxyurea produced fewer posttranslational Hb modifications. In vitro, hydroxyurea reduced the levels of ferryl Hb and shielded its target residue, βCys93, by a process of S-nitrosylation. These mechanistic analyses suggest potential antioxidative therapeutic modalities that may interrupt MP heme-mediated pathophysiology in SCD patients.
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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.