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PubMed: 28088643

Title
Molecular mechanisms of bio-catalysis of heme extraction from hemoglobin.
Journal
Redox biology
Volume
11
Issue
None
Pages
516-523
Date
2017-04-01
Authors
Kurnikova MG | Rafikov R | Rafikova O | Sakipov S

Evidence 515eae18bc
JSON

Extracellular hemoglobin and its degradation products, free heme and iron, are highly toxic due to oxidative stress induction and decrease in nitric oxide availability.

a(CHEBI:"iron(2+)") positiveCorrelation bp(MESH:"Oxidative Stress") View Subject | View Object

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MeSH
Erythrocytes
MeSH
Anemia, Sickle Cell
Text Location
Abstract

a(CHEBI:"iron(2+)") decreases a(CHEBI:"nitric oxide") View Subject | View Object

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MeSH
Erythrocytes
MeSH
Anemia, Sickle Cell
Text Location
Abstract

a(CHEBI:heme) decreases a(CHEBI:"nitric oxide") View Subject | View Object

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MeSH
Erythrocytes
MeSH
Anemia, Sickle Cell
Text Location
Abstract

a(CHEBI:heme) increases bp(MESH:"Oxidative Stress") View Subject | View Object

Appears in Networks:
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MeSH
Erythrocytes
MeSH
Anemia, Sickle Cell
Text Location
Abstract

bp(MESH:"Oxidative Stress") positiveCorrelation a(CHEBI:"iron(2+)") View Subject | View Object

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MeSH
Erythrocytes
MeSH
Anemia, Sickle Cell
Text Location
Abstract

p(HGNC:HBB) increases a(CHEBI:heme) View Subject | View Object

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MeSH
Erythrocytes
MeSH
Anemia, Sickle Cell
Text Location
Abstract

p(HGNC:HBB) decreases a(CHEBI:"nitric oxide") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Erythrocytes
MeSH
Anemia, Sickle Cell
Text Location
Abstract

p(HGNC:HBB) increases bp(MESH:"Oxidative Stress") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Erythrocytes
MeSH
Anemia, Sickle Cell
Text Location
Abstract

p(HGNC:HBB) increases a(CHEBI:"iron(2+)") View Subject | View Object

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Annotations
MeSH
Erythrocytes
MeSH
Anemia, Sickle Cell
Text Location
Abstract

Evidence 915bbc63d2
JSON

Hb and its degradation products – free heme and iron - perpetuate oxidative stress, and together with decreased NO availability promote many SCD complications.

a(CHEBI:"iron(2+)") positiveCorrelation bp(MESH:"Oxidative Stress") View Subject | View Object

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Annotations
MeSH
Erythrocytes
MeSH
Anemia, Sickle Cell
Text Location
Introduction

a(CHEBI:"iron(2+)") decreases a(CHEBI:"nitric oxide") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Erythrocytes
MeSH
Anemia, Sickle Cell
Text Location
Introduction

a(CHEBI:heme) decreases a(CHEBI:"nitric oxide") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Erythrocytes
MeSH
Anemia, Sickle Cell
Text Location
Introduction

a(CHEBI:heme) increases bp(MESH:"Oxidative Stress") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Erythrocytes
MeSH
Anemia, Sickle Cell
Text Location
Introduction

bp(MESH:"Oxidative Stress") positiveCorrelation a(CHEBI:"iron(2+)") View Subject | View Object

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MeSH
Erythrocytes
MeSH
Anemia, Sickle Cell
Text Location
Introduction

Evidence 17aad0988f
JSON

It is well known that in the presence of H2O2 hemoglobin exhibits a peroxidase-like activity, catalyzed by the heme moiety.

a(CHEBI:heme) increases act(a(CHEBI:Peroxidase)) View Subject | View Object

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MeSH
Liver
MeSH
Macrophages
MeSH
Anemia, Sickle Cell
Text Location
Results

Evidence f5137e5b93
JSON

Macrophages and liver cells capture large HP-Hb complexes clearing the plasma from free hemoglobin.

a(MESH:"haptoglobin-hemoglobin complex") decreases p(HGNC:HBB) View Subject | View Object

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MeSH
Liver
MeSH
Macrophages
MeSH
Anemia, Sickle Cell
Text Location
Introduction

Evidence 7b81b97a3b
JSON

Red blood cell hemolysis in sickle cell disease (SCD) releases free hemoglobin.

p(HGNC:HBB) positiveCorrelation path(MESH:Hemolysis) View Subject | View Object

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MeSH
Erythrocytes
MeSH
Anemia, Sickle Cell
Text Location
Abstract

path(MESH:Hemolysis) positiveCorrelation p(HGNC:HBB) View Subject | View Object

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MeSH
Erythrocytes
MeSH
Anemia, Sickle Cell
Text Location
Abstract

Evidence fd488072f9
JSON

Extracellular Hb exhibits a highly toxic nature by scavenging Nitric Oxide (NO) that reduces its bioavailability [1].

p(HGNC:HBB) decreases a(CHEBI:"nitric oxide") View Subject | View Object

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MeSH
Erythrocytes
MeSH
Anemia, Sickle Cell
Text Location
Introduction

Evidence fb442397b6
JSON

However, no changes in peroxidase activity were observed after incubation with haptoglobin or hemopexin (Fig. 2).

p(HGNC:HPX) causesNoChange act(a(CHEBI:Peroxidase)) View Subject | View Object

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MeSH
Liver
MeSH
Macrophages
MeSH
Anemia, Sickle Cell
Text Location
Results

p(HGNC:HP) causesNoChange act(a(CHEBI:Peroxidase)) View Subject | View Object

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Annotations
MeSH
Liver
MeSH
Macrophages
MeSH
Anemia, Sickle Cell
Text Location
Results

Evidence b9f5266f34
JSON

At the same time, heme bound to NEAT does not catalyze the peroxidase reaction due to inability to interact with H2O2.

complex(a(CHEBI:heme), p(INTERPRO:"NEAT domain")) decreases act(a(CHEBI:Peroxidase)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Liver
MeSH
Macrophages
MeSH
Anemia, Sickle Cell
Text Location
Results

Evidence cc61c1c088
JSON

This ability of NEAT can decrease the level of NO scavenging and oxidative stress in SCD.

complex(a(CHEBI:heme), p(INTERPRO:"NEAT domain")) increases a(CHEBI:"nitric oxide") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Liver
MeSH
Macrophages
MeSH
Anemia, Sickle Cell
Text Location
Discussion

complex(a(CHEBI:heme), p(INTERPRO:"NEAT domain")) decreases bp(MESH:"Oxidative Stress") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Liver
MeSH
Macrophages
MeSH
Anemia, Sickle Cell
Text Location
Discussion

Evidence 9d013162f6
JSON

Our data demonstrate a significant decrease in peroxidase activity of hemoglobin incubated with NEATHP, indicating heme transfer.

p(INTERPRO:"NEAT domain") decreases act(a(CHEBI:Peroxidase)) View Subject | View Object

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MeSH
Liver
MeSH
Macrophages
MeSH
Anemia, Sickle Cell
Text Location
Results

Evidence 58a0248162
JSON

Therefore, we demonstrated that an active scavenging of heme by NEAT can reduce peroxidase activity of hemoglobin, whereas passive scavengers cannot.

p(INTERPRO:"NEAT domain") decreases act(a(CHEBI:Peroxidase)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Liver
MeSH
Macrophages
MeSH
Anemia, Sickle Cell
Text Location
Results

p(INTERPRO:"NEAT domain") decreases a(CHEBI:heme) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Liver
MeSH
Macrophages
MeSH
Anemia, Sickle Cell
Text Location
Results

Evidence cd7114d713
JSON

It is seen in Fig. 2 that after incubation with NEAT-HP, Hb has decreased the heme content by 85%, which confirms heme removal ability of NEAT-HP construct.

complex(p(HGNC:HP), p(INTERPRO:"NEAT domain")) decreases a(CHEBI:heme) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Liver
MeSH
Macrophages
MeSH
Anemia, Sickle Cell
Text Location
Results

Evidence 8c7482303d
JSON

Moreover, heme scavenging by NEAT-HP markedly decreased hemoglobin-mediated peroxidase activity (Fig. 2), whereas haptoglobin was capable of only a small attenuation of peroxidase activity and hemopexin did not affect it at all.

complex(p(HGNC:HP), p(INTERPRO:"NEAT domain")) decreases act(a(CHEBI:Peroxidase)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Liver
MeSH
Macrophages
MeSH
Anemia, Sickle Cell
Text Location
Discussion

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