ArticleFree radical biology & medicine2017
The mechanism of formation, structure and physiological relevance of covalent hemoglobin attachment to the erythrocyte membrane.
Article in Free radical biology & medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 87 citations in OpenAlex.
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- Main events and mechanism of human erythrocyte ageing.Expert reviews in molecular medicine · 2026Review
- Redox Homeostasis in Red Blood Cells: From Molecular Mechanisms to Antioxidant Strategies.Current issues in molecular biology · 2025Review
- Biopreservation and reversal of oxidative injury during blood storage by a novel curcumin-based gel formulation.Scientific reports · 2024Article
- Effect of ozonation on the phytochemicals of black seed oil and its anti-microbial, anti-oxidant, anti-inflammatory, and anti-neoplastic activities in vitro.Scientific reports · 2024Article
- Taming hemoglobin chemistry-a new hemoglobin-based oxygen carrier engineered with both decreased rates of nitric oxide scavenging and lipid oxidation.Experimental & molecular medicine · 2024Article
- Chloride Gradient Is Involved in Ammonium Influx in Human Erythrocytes.International journal of molecular sciences · 2024Article
- Hemoglobin Binding to the Red Blood Cell (RBC) Membrane Is Associated with Decreased Cell Deformability.International journal of molecular sciences · 2024Article
- Catalase, Glutathione Peroxidase, and Peroxiredoxin 2 in Erythrocyte Cytosol and Membrane in Hereditary Spherocytosis, Sickle Cell Disease, and β-Thalassemia.Antioxidants (Basel, Switzerland) · 2024Article
- Biopreservation and Reversal of Oxidative Injury During Blood Storage by a Novel Curcumin-based Gel Formulation.Research square · 2024Article
- Factors Influencing Venous Remodeling in the Development of Varicose Veins of the Lower Limbs.International journal of molecular sciences · 2024Review
- Impact of cold storage on the oxygenation and oxidation reactions of red blood cells.Frontiers in physiology · 2024Article
- The Impact of CaCells · 2023Article
- Oxidative Stress in Healthy and Pathological Red Blood Cells.Biomolecules · 2023Review
- The Effect of Polyene Antibiotic Amphotericin B on Erythrocyte Cytoarchitectonics and Osmotic Resistance.Bulletin of experimental biology and medicine · 2023Article
- Molecular Basis and Genetic Modifiers of Thalassemia.Hematology/oncology clinics of North America · 2023Review
- Ultraviolet light oxidation of fresh hemoglobin eliminates aggregate formation seen in commercially sourced hemoglobin.Blood cells, molecules & diseases · 2023Article
- 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
- Hemoglobin can Act as a (Pseudo)-PeroxidaseFrontiers in molecular biosciences · 2022Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Covalent hemoglobin binding to membranes leads to band 3 (AE1) clustering and the removal of erythrocytes from the circulation; it is also implicated in blood storage lesions. Damaged hemoglobin, with the heme being in a redox and oxygen-binding inactive hemichrome form, has been implicated as the binding species. However, previous studies used strong non-physiological oxidants. In vivo hemoglobin is constantly being oxidised to methemoglobin (ferric), with around 1% of hemoglobin being in this form at any one time. In this study we tested the ability of the natural oxidised form of hemoglobin (methemoglobin) in the presence or absence of the physiological oxidant hydrogen peroxide to initiate membrane binding. The higher the oxidation state of hemoglobin (from Fe(III) to Fe(V)) the more binding was observed, with approximately 50% of this binding requiring reactive sulphydryl groups. The hemoglobin bound was in a high molecular weight complex containing spectrin, ankyrin and band 4.2, which are common to one of the cytoskeletal nodes. Unusually, we showed that hemoglobin bound in this way was redox active and capable of ligand binding. It can initiate lipid peroxidation showing the potential to cause cell damage. In vivo oxidative stress studies using extreme endurance exercise challenges showed an increase in hemoglobin membrane binding, especially in older cells with lower levels of antioxidant enzymes. These are then targeted for destruction. We propose a model where mild oxidative stress initiates the binding of redox active hemoglobin to the membrane. The maximum lifetime of the erythrocyte is thus governed by the redox activity of the cell; from the moment of its release into the circulation the timer is set.
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Registered trials
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