ArticleFEBS open bio2016
Differential heme release from various hemoglobin redox states and the upregulation of cellular heme oxygenase-1.
Article in FEBS open bio, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 68 citations in OpenAlex.
- The Role of Cytochrome P450 Holoenzyme Metabolism in the Origin of Neuropathologies.International journal of molecular sciences · 2026Review
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- Oxidized Cell-Free Hemoglobin Induces Mitochondrial Dysfunction by Activation of the Mitochondrial Permeability Transition Pore in the Pulmonary Microvasculature.Microcirculation (New York, N.Y. : 1994) · 2025Article
- Extremophilic hemoglobins: The structure of Shewanella benthica truncated hemoglobin N.The Journal of biological chemistry · 2025Article
- Precise Engineering and Efficient Biosynthesis of Robust and High-Activity Human Haemoglobin for Artificial Oxygen Carriers.Microbial biotechnology · 2025Article
- Effects of chemical modifications on hemoglobin's toxicity towards human cardiac myocytes.Frontiers in molecular biosciences · 2025Article
- Coadministration of PEGylated apohemoglobin and haptoglobin can limit vascular dysfunction in the microcirculation and prevent acute inflammation.Journal of applied physiology (Bethesda, Md. : 1985) · 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
- The Key Role of GSH in Keeping the Redox Balance in Mammalian Cells: Mechanisms and Significance of GSH in Detoxification via Formation of Conjugates.Antioxidants (Basel, Switzerland) · 2023Review
- Interactions of reactive sulfur species with metalloproteins.Redox biology · 2023Review
- Oxidized hemoglobin triggers polyreactivity and autoreactivity of human IgG via transfer of heme.Communications biology · 2023Article
- Ultraviolet light oxidation of fresh hemoglobin eliminates aggregate formation seen in commercially sourced hemoglobin.Blood cells, molecules & diseases · 2023Article
- Glutathione-Hemin/Hematin Adduct Formation to Disintegrate Cytotoxic Oxidant Hemin/Hematin in Human K562 Cells and Red Blood Cells' Hemolysates: Impact of Glutathione on the Hemolytic Disorders and Homeostasis.Antioxidants (Basel, Switzerland) · 2022Article
- New Insights into Hemopexin-Binding to Hemin and Hemoglobin.International journal of molecular sciences · 2022Article
- Melatonin: Regulation of Prion Protein Phase Separation in Cancer Multidrug Resistance.Molecules (Basel, Switzerland) · 2022Review
- Low grade intravascular hemolysis associates with peripheral nerve injury in type 2 diabetes.PloS one · 2022Article
- Stealthy microbes: HowFrontiers in cellular and infection microbiology · 2022Review
- Ten years of FEBS Open Bio.FEBS open bio · 2021Article
- A Slam-dependent hemophore contributes to heme acquisition in the bacterial pathogen Acinetobacter baumannii.Nature communications · 2021Article
- Oxidation of Hemoglobin Drives a Proatherogenic Polarization of Macrophages in Human Atherosclerosis.Antioxidants & redox signaling · 2021Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite advances in our understanding of the oxidative pathways mediated by free hemoglobin (Hb), the precise contribution of its highly reactive redox forms to tissue and organ toxicities remains ambiguous. Heme, a key degradation byproduct of Hb oxidation, has recently been recognized as a damage-associated molecular pattern (DAMP) molecule, able to trigger inflammatory responses. Equally damaging is the interaction of the highly redox active forms of Hb with other biological molecules. We determined the kinetics of heme loss from individual Hb redox states-ferrous (Fe(2+)), ferric (Fe(3+)), and ferryl (Fe(4+))-using two different heme receptor proteins: hemopexin (Hxp), a naturally occurring heme scavenger in plasma, and a double mutant (H64Y/V86F), apomyoglobin (ApoMb), which avidly binds heme released from Hb. We show for the first time that ferric Hb (Fe(3+)) loses heme at rates substantially higher than that of ferryl Hb (Fe(4+)). This was also supported by a higher expression of heme oxygenase-1 (HO-1) when ferric Hb was added to cultured lung alveolar epithelial cells (E10). The reported cytotoxicity of Hb may therefore be attributed to a combination of accelerated heme loss from the ferric form and protein radical formation associated with ferryl Hb. Targeted therapeutic interventions can therefore be designed to curb specific oxidative pathways of Hb in hemolytic anemias and when Hb is used as an oxygen-carrying therapeutic.
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