ArticleThe Journal of biological chemistry2015
Sickle Cell Hemoglobin in the Ferryl State Promotes βCys-93 Oxidation and Mitochondrial Dysfunction in Epithelial Lung Cells (E10).
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Relevance of Plasma Homocysteine and Methylenetetrahydrofolate Reductase 677TT Genotype in Sickle Cell Disease: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2022Pooled it
- The Role of Cytochrome P450 Holoenzyme Metabolism in the Origin of Neuropathologies.International journal of molecular sciences · 2026Review
- Recombinant Hemoglobin rHb0.1 with Cross-Linked Alpha Subunits Preferentially Crystallizes in the βACS omega · 2026Article
- A novel transdermal curcumin gel shows potential in improving cardiac bioenergetic functions in Berkeley sickle cell mice.Blood vessels, thrombosis & hemostasis · 2026Article
- Article
- The involvement of mitochondria in erythrocyte pathology and diseases: from mechanisms to therapeutic strategies.Clinical and experimental medicine · 2025Review
- Crosstalk Between Sickle Cell Disease and Ferroptosis.International journal of molecular sciences · 2025Review
- Effects of chemical modifications on hemoglobin's toxicity towards human cardiac myocytes.Frontiers in molecular biosciences · 2025Article
- Ferroptosis as an emerging target in sickle cell disease.Current research in toxicology · 2024Article
- Mitochondria: Emerging Consequential in Sickle Cell Disease.Journal of clinical medicine · 2023Review
- Oxidative Reactions Catalyzed by Hydrogen Peroxide Produced by Streptococcus pneumoniae and Other Streptococci Cause the Release and Degradation of Heme from Hemoglobin.Infection and immunity · 2022Article
- Temporal brain transcriptome analysis reveals key pathological events after germinal matrix hemorrhage in neonatal rats.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Review
- Association of sickle cell trait with β-cell dysfunction and physical activity in adults living with and without HIV in Tanzania.APMIS : acta pathologica, microbiologica, et immunologica Scandinavica · 2022Article
- Oxidation reactions of cellular and acellular hemoglobins: Implications for human health.Frontiers in medical technology · 2022Review
- Hemoglobin can Act as a (Pseudo)-PeroxidaseFrontiers in molecular biosciences · 2022Article
- Caffeic acid: an antioxidant with novel antisickling properties.FEBS open bio · 2021Article
- Sickle Cell Disease: Role of Oxidative Stress and Antioxidant Therapy.Antioxidants (Basel, Switzerland) · 2021Review
- βCysteine 93 in human hemoglobin: a gateway to oxidative stability in health and disease.Laboratory investigation; a journal of technical methods and pathology · 2021Review
- The Providence Mutation (βK82D) in Human Hemoglobin Substantially Reduces βCysteine 93 Oxidation and Oxidative Stress in Endothelial Cells.International journal of molecular sciences · 2020Article
- Effects of α subunit substitutions on the oxidation of βCys93 and the stability of sickle cell hemoglobin.Redox report : communications in free radical research · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Polymerization of intraerythrocytic deoxyhemoglobin S (HbS) is the primary molecular event that leads to hemolytic anemia in sickle cell disease (SCD). We reasoned that HbS may contribute to the complex pathophysiology of SCD in part due to its pseudoperoxidase activity. We compared oxidation reactions and the turnover of oxidation intermediates of purified human HbS and HbA. Hydrogen peroxide (H2O2) drives a catalytic cycle that includes the following three distinct steps: 1) initial oxidation of ferrous (oxy) to ferryl Hb; 2) autoreduction of the ferryl intermediate to ferric (metHb); and 3) reaction of metHb with an additional H2O2 molecule to regenerate the ferryl intermediate. Ferrous and ferric forms of both proteins underwent initial oxidation to the ferryl heme in the presence of H2O2 at equal rates. However, the rate of autoreduction of ferryl to the ferric form was slower in the HbS solutions. Using quantitative mass spectrometry and the spin trap, 5,5-dimethyl-1-pyrroline-N-oxide, we found more irreversibly oxidized βCys-93in HbS than in HbA. Incubation of the ferric or ferryl HbS with cultured lung epithelial cells (E10) induced a drop in mitochondrial oxygen consumption rate and impairment of cellular bioenergetics that was related to the redox state of the iron. Ferryl HbS induced a substantial drop in the mitochondrial transmembrane potential and increases in cytosolic heme oxygenase (HO-1) expression and mitochondrial colocalization in E10 cells. Thus, highly oxidizing ferryl Hb and heme, the product of oxidation, may be central to the evolution of vasculopathy in SCD and may suggest therapeutic modalities that interrupt heme-mediated inflammation.
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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.