The role of redox-dependent mechanisms in heme release from hemoglobin and erythrocyte hemolysates

Oh, Joo–Yeun; Williams, Austin; Patel, Rakesh P.

doi:10.1016/j.abb.2018.12.005

Cited by 14 publications

(16 citation statements)

References 41 publications

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“…Heme loss was studied from the ferric Hb as this rate is far greater than the loss from the ferrous redox state 51 and is likely to be the physiologically relevant rate for an HBOC in vivo. 51,52 The effect of mutations on the rate of globin autoxidation is less well characterized than effects on oxygen affinity. 40,42 Although some globins with high oxygen affinity have very low autoxidation rates, 53 no Hb mutations that would be able to mirror these effects have been engineered.…”

Section: Biomaterials Sciencementioning

confidence: 99%

Engineering hemoglobin to enable homogenous PEGylation without modifying protein functionality

et al. 2020

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Section: Biomaterials Sciencementioning

confidence: 99%

Engineering hemoglobin to enable homogenous PEGylation without modifying protein functionality

et al. 2020

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“…Under normal physiological conditions, Hb is encapsulated in red blood cells, which is widely acknowledged. Intravascular hemolysis can occur in a pathological state, such as during tissue injury, stored RBC transfusions, or hemolytic microbe infection ( 2 , 33 ). Exposure to high levels of free Hb or heme occurs in several disease states (such as sickle cell disease and kidney injury-associated diseases), which is widely studied in mammal models.…”

Section: Discussionmentioning

confidence: 99%

“…Hemoglobin (Hb) is an iron-containing metalloprotein whose main biological function is oxygen transport. Under normal circumstances, it is sequestered in the erythrocytes by a highly efficient antioxidant system to prevent vasculature or other tissues from exposure to this pro-oxidative and proinflammatory protein (1,2). However, the extent of hemolysis at the different treatment time points was evaluated using plasma (2)(3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

“…Under normal circumstances, it is sequestered in the erythrocytes by a highly efficient antioxidant system to prevent vasculature or other tissues from exposure to this pro-oxidative and proinflammatory protein (1,2). However, the extent of hemolysis at the different treatment time points was evaluated using plasma (2)(3)(4)(5). Due to the Fenton reaction and pseudoperoxidase (POX) activity [triggered synergistically by microbial proteases and pathogen-associated molecular patterns (PAMPs), such as lipopolysaccharide (LPS) and lipoteichoic acid (LTA)], ferrous Hb-Fe 2+ is prone to auto-oxidation to ferric Hb-Fe 3+ (also referred to as methemoglobin) and to ferryl Hb-Fe 4+ , with the oxidized Hb also releasing heme (which is highly redox-reactive and induces oxidative stress) into plasma or tissues (4), leading to the formation of superoxide anion and other reactive derivatives such as hydroxyl radical and hypohalous acid (6)(7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

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The Oxidative Injury of Extracellular Hemoglobin Is Associated With Reactive Oxygen Species Generation of Grass Carp (Ctenopharyngodon idella)

Qin

Yang

et al. 2022

Front. Immunol.

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Intravascular hemolysis is a fundamental feature of hemorrhagic venereal infection or tissue and releases the endogenous damage-associated molecular pattern hemoglobin (Hb) into the plasma or tissues, which results in systemic inflammation, vasomotor dysfunction, thrombophilia, and proliferative vasculopathy. However, how the cytotoxic Hb affects the tissues of grass carp remains unclear. Here, we established a hemolysis model in grass carp by injecting phenylhydrazine (PHZ). The data revealed that the PHZ-induced hemolysis increased the content of Hb and activated the antioxidant system in plasma. The histopathology analysis data showed that the PHZ-induced hemolysis increased the accumulation of Hb and iron both in the head and middle kidney. The results of quantitative real-time PCR (qRT-PCR) detection suggested that the hemolysis upregulated the expressions of iron metabolism-related genes. In addition, the immunofluorescence and immunohistochemistry data revealed that the hemolysis caused an obvious deposition of collagen fiber, malondialdehyde (MDA), and 4-hydroxynonenal (4-HNE) accumulation and increased the content of oxidative-related enzymes such as β-galactosidase (β-GAL), lipid peroxide (LPO), and MDA in both the head and middle kidney. Furthermore, the PHZ-induced hemolysis significantly increased the production of reactive oxygen species (ROS), which resulted in apoptosis and modulated the expressions of cytokine-related genes. Taken together, excess of Hb released from hemolysis caused tissue oxidative damage, which may be associated with ROS and inflammation generation.

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“…Globin radicals are reactive intermediates which react with each other in which reactions with the unpaired electrons located on the globin chains form new covalent bonds between the Hb subunits yielding covalently crosslinked Hb forms (reviewed in [3]). Importantly, Hb oxidation is associated with remarkable conformational distortion weakening the noncovalent globin-heme interaction, eventually leading to the release of the heme moiety [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Formation and Detection of Highly Oxidized Hemoglobin Forms in Biological Fluids during Hemolytic Conditions

Nyakundi

Erdei

Tóth

et al. 2020

Oxidative Medicine and Cellular Longevity

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Hemolytic diseases are characterized by an accelerated breakdown of red blood cells (RBCs) and the release of hemoglobin (Hb). Following, RBC lysis Hb oxidation occurs with the formation of different redox states of Hb (metHb and ferrylHb) and the release of heme. ferrylHb is unstable and decomposes to metHb with the concomitant formation of globin radicals and eventually covalently crosslinked Hb multimers. The goal of the present study was to determine the concentrations of the different redox states of Hb in biological samples during hemolytic conditions. We used plasma and urine samples of mice with intravascular hemolysis and human cerebrospinal fluid (CSF) samples following intraventricular hemorrhage. Because ferrylHb is highly unstable, we also addressed the fate of this species. metHb and free heme time-dependently accumulate in plasma and CSF samples following intravascular hemolysis and intraventricular hemorrhage, respectively. ferrylHb is hardly detectable in the biological samples during hemolytic conditions. Under in vitro conditions, ferrylHb decomposes quickly to metHb, which process is associated with the formation of covalently crosslinked Hb multimers. We detected these covalently crosslinked Hb multimers in plasma, urine, and CSF samples during hemolytic conditions. Because globin modification is specific for these Hb forms, we propose to call this heterogeneous form of Hb produced during ferrylHb decomposition as globin-modified oxidized Hb (gmoxHb). Understanding the formation and the contribution of gmoxHb species to the pathogenesis of hemolytic conditions could have therapeutic implications in the treatment of hemolytic diseases.

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The role of redox-dependent mechanisms in heme release from hemoglobin and erythrocyte hemolysates

Cited by 14 publications

References 41 publications

Engineering hemoglobin to enable homogenous PEGylation without modifying protein functionality

Engineering hemoglobin to enable homogenous PEGylation without modifying protein functionality

The Oxidative Injury of Extracellular Hemoglobin Is Associated With Reactive Oxygen Species Generation of Grass Carp (Ctenopharyngodon idella)

Formation and Detection of Highly Oxidized Hemoglobin Forms in Biological Fluids during Hemolytic Conditions

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