ArticleScientific reports2020
Post-translational modification as a response to cellular stress induced by hemoglobin oxidation in sickle cell disease.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 41 citations in OpenAlex.
- Post-translational Modifications in Proteins: Prediction Methods, Biological Functions, and Diseases.MedComm · 2026Review
- Breaking the vicious cycle in sickle cell disease: Redox stress impairs red blood cell rheology and promotes lung vasocongestion.Free radical biology & medicine · 2025Article
- Advances in the Study of Protein Deamidation: Unveiling Its Influence on Aging, Disease Progression, Forensics and Therapeutic Efficacy.Proteomes · 2025Review
- Unraveling the multifaceted roles of peroxiredoxins in sickle cell anemia: implications in redox and inflammation adaptations.Annals of hematology · 2025Article
- Effects of chemical modifications on hemoglobin's toxicity towards human cardiac myocytes.Frontiers in molecular biosciences · 2025Article
- Biopreservation and reversal of oxidative injury during blood storage by a novel curcumin-based gel formulation.Scientific reports · 2024Article
- Top-Down Proteomics Identifies Plasma Proteoform Signatures of Liver Cirrhosis Progression.Molecular & cellular proteomics : MCP · 2024Article
- Biopreservation and Reversal of Oxidative Injury During Blood Storage by a Novel Curcumin-based Gel Formulation.Research square · 2024Article
- Interplay between α-thalassemia and β-hemoglobinopathies: Translating genotype-phenotype relationships into therapies.HemaSphere · 2024Article
- Impact of cold storage on the oxygenation and oxidation reactions of red blood cells.Frontiers in physiology · 2024Article
- Changes in hemoglobin oxidation and band 3 during blood storage impact oxygen sensing and mitochondrial bioenergetic pathways in the human pulmonary arterial endothelial cell model.Frontiers in physiology · 2023Article
- HIF-1α-Dependent Metabolic Reprogramming, Oxidative Stress, and Bioenergetic Dysfunction in SARS-CoV-2-Infected Hamsters.International journal of molecular sciences · 2022Article
- Redox stress in COVID-19: Implications for hematologic disorders.Best practice & research. Clinical haematology · 2022Review
- Mitapivat increases ATP and decreases oxidative stress and erythrocyte mitochondria retention in a SCD mouse model.Blood cells, molecules & diseases · 2022Article
- Measurement of erythrocyte membrane mannoses to assess splenic function.British journal of haematology · 2022Article
- Redox Balance in β-Thalassemia and Sickle Cell Disease: A Love and Hate Relationship.Antioxidants (Basel, Switzerland) · 2022Review
- Hemoglobin Oxidation Reactions in Stored Blood.Antioxidants (Basel, Switzerland) · 2022Article
- Proteomic Analysis of the Role of the Adenylyl Cyclase-cAMP Pathway in Red Blood Cell Mechanical Responses.Cells · 2022Article
- Hemoglobin can Act as a (Pseudo)-PeroxidaseFrontiers in molecular biosciences · 2022Article
- Oxidation reactions of cellular and acellular hemoglobins: Implications for human health.Frontiers in medical technology · 2022Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Intracellular oxidative stress and oxidative modification of sickle hemoglobin (HbS) play a role in sickle cell disease (SCD) pathogenesis. Recently, we reported that Hb-dependent oxidative stress induced post-translational modifications (PTMs) of Hb and red blood cell (RBC) membrane proteins of transgenic SCD mice. To identify the mechanistic basis of these protein modifications, we followed in vitro oxidative changes occurring in intracellular Hb obtained from RBCs and RBC-derived microparticles (MPs) from the blood of 23 SCD patients (HbSS) of which 11 were on, and 12, off hydroxyurea (HU) treatment, and 5 ethnic matched controls. We used mass spectrometry-based proteomics to characterize these oxidative PTMs on a cross-sectional group of these patients (n = 4) and a separate subgroup of patients (n = 2) studied prior to initiation and during HU treatment. Collectively, these data indicated that band-3 and its interaction network involved in MPs formation exhibited more protein phosphorylation and ubiquitination in SCD patients than in controls. HU treatment reversed these oxidative PTMs back to level observed in controls. These PTMs were also confirmed using orthogonal immunoprecipitation experiments. Moreover, we observed specific markers reflective of oxidative stress, including irreversible oxidation of βCys93 and ubiquitination of Hb βLys145 (and βLys96). Overall, these studies strongly suggest that extensive erythrocyte membrane protein phosphorylation and ubiquitination are involved in SCD pathogenesis and provide further insight into the multifaceted effects of HU treatment.
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