ArticleRedox biology2016
Oxidative instability of hemoglobin E (β26 Glu→Lys) is increased in the presence of free α subunits and reversed by α-hemoglobin stabilizing protein (AHSP): Relevance to HbE/β-thalassemia.
Article in Redox biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- The Role of Cytochrome P450 Holoenzyme Metabolism in the Origin of Neuropathologies.International journal of molecular sciences · 2026Review
- Multiomics analysis of red blood cells reveals thalassemia severity beyond globin gene mutations.Blood advances · 2026Article
- Recombinant Hemoglobin rHb0.1 with Cross-Linked Alpha Subunits Preferentially Crystallizes in the βACS omega · 2026Article
- Hemoglobin Variants as Targets for Stabilizing Drugs.Molecules (Basel, Switzerland) · 2025Review
- βCysteine 93 in human hemoglobin: a gateway to oxidative stability in health and disease.Laboratory investigation; a journal of technical methods and pathology · 2021Review
- Hemoglobin oxidation generates globin-derived peptides in atherosclerotic lesions and intraventricular hemorrhage of the brain, provoking endothelial dysfunction.Laboratory investigation; a journal of technical methods and pathology · 2020Article
- Alpha-hemoglobin-stabilizing protein (AHSP): a modulatory factor in β-thalassemia.International journal of hematology · 2020Review
- Melting of Hemoglobin in Native Solutions as measured by IMS-MS.Analytical chemistry · 2020Article
- Impacts of low concentration surfactant on red blood cell dielectrophoretic responses.Biomicrofluidics · 2019Article
- Oxidative pathways in the sickle cell and beyond.Blood cells, molecules & diseases · 2018Review
- Exploring Oxidative Reactions in Hemoglobin Variants Using Mass Spectrometry: Lessons for Engineering Oxidatively Stable Oxygen Therapeutics.Antioxidants & redox signaling · 2017Review
- HbE/β-Thalassemia and Oxidative Stress: The Key to Pathophysiological Mechanisms and Novel Therapeutics.Antioxidants & redox signaling · 2017Review
- Determination of extinction coefficients of human hemoglobin in various redox states.Analytical biochemistry · 2017Article
- Oxidized Mutant Human Hemoglobins S and E Induce Oxidative Stress and Bioenergetic Dysfunction in Human Pulmonary Endothelial Cells.Frontiers in physiology · 2017Article
- Differential heme release from various hemoglobin redox states and the upregulation of cellular heme oxygenase-1.FEBS open bio · 2016Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
When adding peroxide (H2O2), β subunits of hemoglobin (Hb) bear the burden of oxidative changes due in part to the direct oxidation of its Cys93. The presence of unpaired α subunits within red cells and/or co-inheritance of another β subunit mutant, HbE (β26 Glu→Lys) have been implicated in the pathogenesis and severity of β thalassemia. We have found that although both HbA and HbE autoxidize at initially comparable rates, HbE loses heme at a rate almost 2 fold higher than HbA due to unfolding of the protein. Using mass spectrometry and the spin trap, DMPO, we were able to quantify irreversible oxidization of βCys93 to reflect oxidative instability of β subunits. In the presence of free α subunits and H2O2, both HbA and HbE showed βCys93 oxidation which increased with higher H2O2 concentrations. In the presence of Alpha-hemoglobin stabilizing protein (AHSP), which stabilizes the α-subunit in a redox inactive hexacoordinate conformation (thus unable to undergo the redox ferric/ferryl transition), Cys93 oxidation was substantially reduced in both proteins. These experiments establish two important features that may have relevance to the mechanistic understanding of these two inherited hemoglobinopathies, i.e. HbE/β thalassemia: First, a persistent ferryl/ferryl radical in HbE is more damaging to its own β subunit (i.e., βCys93) than HbA. Secondly, in the presence of excess free α-subunit and under the same oxidative conditions, these events are substantially increased for HbE compared to HbA, and may therefore create an oxidative milieu affecting the already unstable HbE.
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