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a(CHEBI:methemoglobin)

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Entity

Name
methemoglobin
Namespace
chebi
Namespace Version
20180906
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/chebi-names.belns

Appears in Networks 1

Heme Curation v0.0.1-dev

Mechanistic knowledge surrounding heme

In-Edges 15

a(CHEBI:"hydrogen peroxide") positiveCorrelation a(CHEBI:methemoglobin) View Subject | View Object

However, metHb levels may increase when there is an increase in Hb autoxidation and the concomitant generation of H2O2 that is not scavenged by antioxidant defense enzymes making it more difficult for metHb-reductase to keep up with the metHb produced. PubMed:23215741

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Text Location
Results

a(CHEBI:oxyhemoglobin) increases a(CHEBI:methemoglobin) View Subject | View Object

For example, autooxidation of oxyhemoglobin (HbO2) or oxymyoglobin (MbO2) produces met-Hb or met-Mb, respectively, and superoxide radicals (O2•−, HO2•) via electron transfer [3,4]. PubMed:24486321

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Text Location
Introduction

a(HM:"stored erythrocytes") positiveCorrelation a(CHEBI:methemoglobin) View Subject | View Object

Figures 2A-F show changes in oxyhemoglobin, methemoglobin and free heme in both the intraerythrocytic and supernatant fractions in both d7 and d35 RBC. Significant storage-dependent increases for all species in the cell-free fraction were observed, with no storage-dependent differences observed in the erythrocyte. PubMed:26202471

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a(HM:"stored erythrocytes") positiveCorrelation a(CHEBI:methemoglobin) View Subject | View Object

Consistent with our previous studies [25,36], free oxyHb, metHb, and heme levels were increased after 14 d of RBC storage, being 930 ± 125 μM, 40.3 ± 8.8 μM, and 168 ± 44.7 μM, respectively (mean ± SEM, n = 7). PubMed:29522519

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Text Location
Results

a(MESH:"Blood Transfusion") positiveCorrelation a(CHEBI:methemoglobin) View Subject | View Object

Electron paramagnetic resonance (EPR) spectra of renal tissues from old blood-transfused animals were recorded at 6K and showed a strong signal around g=6, which is indicative of high-spin ferric Hb(Fe3+) (Figure 3a). PubMed:26794659

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Annotations
Cell Ontology (CL)
epithelial cell
MeSH
Kidney
Text Location
Results

a(MESH:"Blood Transfusion") positiveCorrelation a(CHEBI:methemoglobin) View Subject | View Object

First, quantification of high-spin ferric Hb(Fe3+), which is the initial Hb oxidation product resulting from the oxidation of ferrous oxyHb(Fe2+), in the kidneys of the old blood-transfused guinea pigs suggests very high concentrations of ferric Hb can accumulate in renal tissues at 24 h after old blood transfusion. PubMed:26794659

Appears in Networks:
Annotations
Cell Ontology (CL)
epithelial cell
MeSH
Kidney
Text Location
Discussion

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

The second biochemical process relates to the ability of Hb to facilitate oxidative reactions outside of the reducing environment of the RBC, leading to the accumulation of ferric metHb(Fe3+) in tissue.24 PubMed:29610666

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Mitochondria
Text Location
Discussion

complex(a(CHEBI:"iron trichloride"), a(CHEBI:methemoglobin)) hasComponent a(CHEBI:methemoglobin) View Subject | View Object

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complex(a(CHEBI:methemoglobin), p(HGNC:HPX)) hasComponent a(CHEBI:methemoglobin) View Subject | View Object

Appears in Networks:

p(HGNC:HP) negativeCorrelation a(CHEBI:methemoglobin) View Subject | View Object

No high-spin ferric Hb was present in the control tissues or renal tissues of old blood-transfused, Hp-treated guinea pigs. PubMed:26794659

Appears in Networks:
Annotations
Cell Ontology (CL)
epithelial cell
MeSH
Kidney
Text Location
Results

p(MGI:Prdx2) negativeCorrelation a(CHEBI:methemoglobin) View Subject | View Object

As shown in Figure 2, the mean metHb levels were also significantly increased in PRDX2 knockout mice, but not in SOD1 knockout mice compared with control mice. PubMed:23215741

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Annotations
Cell Ontology (CL)
erythrocyte
Text Location
Results

path(MESH:Hemolysis) positiveCorrelation a(CHEBI:methemoglobin) View Subject | View Object

The above-discussed findings provide strong in vivo evidence that high concentrations of ferric Hb(Fe3+) and free heme can accumulate in the renal cortex during hemolysis. PubMed:26794659

Appears in Networks:
Annotations
Cell Ontology (CL)
epithelial cell
MeSH
Kidney Cortex
Text Location
Discussion

rxn(reactants(a(CHEBI:"nitric oxide"), a(CHEBI:oxyhemoglobin)), products(a(CHEBI:methemoglobin), a(CHEBI:nitrate))) hasProduct a(CHEBI:methemoglobin) View Subject | View Object

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rxn(reactants(a(CHEBI:"nitric oxide"), p(HGNC:HBB)), products(a(CHEBI:methemoglobin), a(CHEBI:nitrate))) hasProduct a(CHEBI:methemoglobin) View Subject | View Object

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rxn(reactants(p(HGNC:HBB)), products(a(CHEBI:methemoglobin))) hasProduct a(CHEBI:methemoglobin) View Subject | View Object

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Out-Edges 16

a(CHEBI:methemoglobin) positiveCorrelation a(CHEBI:"hydrogen peroxide") View Subject | View Object

However, metHb levels may increase when there is an increase in Hb autoxidation and the concomitant generation of H2O2 that is not scavenged by antioxidant defense enzymes making it more difficult for metHb-reductase to keep up with the metHb produced. PubMed:23215741

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Text Location
Results

a(CHEBI:methemoglobin) negativeCorrelation p(MGI:Prdx2) View Subject | View Object

As shown in Figure 2, the mean metHb levels were also significantly increased in PRDX2 knockout mice, but not in SOD1 knockout mice compared with control mice. PubMed:23215741

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Text Location
Results

deg(a(CHEBI:methemoglobin)) increases a(CHEBI:heme) View Subject | View Object

Hp bound metHb and prevented heme loss and hemopexin captures any free heme released from metHb during its denaturation. PubMed:24486321

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

a(CHEBI:methemoglobin) increases deg(a(CHEBI:heme)) View Subject | View Object

In subsequent reactions, metHb or metHb-derived heme participates in redox chain reactions that lead to the accumulation of modified lipids and proteins, as well as to heme degradation and to the release of free iron.19,25 PubMed:29610666

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Mitochondria
Text Location
Discussion

a(CHEBI:methemoglobin) positiveCorrelation a(HM:"stored erythrocytes") View Subject | View Object

Figures 2A-F show changes in oxyhemoglobin, methemoglobin and free heme in both the intraerythrocytic and supernatant fractions in both d7 and d35 RBC. Significant storage-dependent increases for all species in the cell-free fraction were observed, with no storage-dependent differences observed in the erythrocyte. PubMed:26202471

Appears in Networks:
Annotations
Text Location
Results

a(CHEBI:methemoglobin) positiveCorrelation a(HM:"stored erythrocytes") View Subject | View Object

Consistent with our previous studies [25,36], free oxyHb, metHb, and heme levels were increased after 14 d of RBC storage, being 930 ± 125 μM, 40.3 ± 8.8 μM, and 168 ± 44.7 μM, respectively (mean ± SEM, n = 7). PubMed:29522519

Appears in Networks:
Annotations
Text Location
Results

a(CHEBI:methemoglobin) positiveCorrelation a(MESH:"Blood Transfusion") View Subject | View Object

Electron paramagnetic resonance (EPR) spectra of renal tissues from old blood-transfused animals were recorded at 6K and showed a strong signal around g=6, which is indicative of high-spin ferric Hb(Fe3+) (Figure 3a). PubMed:26794659

Appears in Networks:
Annotations
Cell Ontology (CL)
epithelial cell
MeSH
Kidney
Text Location
Results

a(CHEBI:methemoglobin) positiveCorrelation a(MESH:"Blood Transfusion") View Subject | View Object

First, quantification of high-spin ferric Hb(Fe3+), which is the initial Hb oxidation product resulting from the oxidation of ferrous oxyHb(Fe2+), in the kidneys of the old blood-transfused guinea pigs suggests very high concentrations of ferric Hb can accumulate in renal tissues at 24 h after old blood transfusion. PubMed:26794659

Appears in Networks:
Annotations
Cell Ontology (CL)
epithelial cell
MeSH
Kidney
Text Location
Discussion

a(CHEBI:methemoglobin) negativeCorrelation p(HGNC:HP) View Subject | View Object

No high-spin ferric Hb was present in the control tissues or renal tissues of old blood-transfused, Hp-treated guinea pigs. PubMed:26794659

Appears in Networks:
Annotations
Cell Ontology (CL)
epithelial cell
MeSH
Kidney
Text Location
Results

a(CHEBI:methemoglobin) positiveCorrelation path(MESH:Hemolysis) View Subject | View Object

The above-discussed findings provide strong in vivo evidence that high concentrations of ferric Hb(Fe3+) and free heme can accumulate in the renal cortex during hemolysis. PubMed:26794659

Appears in Networks:
Annotations
Cell Ontology (CL)
epithelial cell
MeSH
Kidney Cortex
Text Location
Discussion

a(CHEBI:methemoglobin) increases act(a(MESH:"Mitogen-Activated Protein Kinases")) View Subject | View Object

We also found that HbFe21 and HbFe31 activate NF-kB and mitogen-activated protein kinase pathways, as shown by phosphorylation of NF-kB p65 subunit and p44/42, respectively (Figure E3) as noted previously (31). PubMed:26974230

Appears in Networks:
Annotations
MeSH
Alveolar Epithelial Cells
Text Location
Results

a(CHEBI:methemoglobin) increases p(MGI:Hmox1) View Subject | View Object

Exposure to ferric Hb (HbFe31) induced a significant expression in HO-1 protein– (15.1761.04-fold) when compared with HbFe21 (9.3260.76-fold)- induced expression (Figure 2C). PubMed:26974230

Appears in Networks:
Annotations
MeSH
Alveolar Epithelial Cells
Text Location
Results

a(CHEBI:methemoglobin) increases p(MGI:Hmox1) View Subject | View Object

We found a significant enrichment of HO-1 in the mitochondrial, but not in the cytosolic fractions after exposure to HbFe21 and HbFe31 (Figures 3A and 3B). PubMed:26974230

Appears in Networks:
Annotations
MeSH
Mitochondria
Text Location
Results

a(CHEBI:methemoglobin) increases p(MGI:Fth1) View Subject | View Object

Similarly, HbFe31 induced a significant expression H-ferritin protein (60.4062.76-fold) when compared with a 25.25 (61.91)-fold induction by HbFe21 (Figure 2D). PubMed:26974230

Appears in Networks:
Annotations
MeSH
Alveolar Epithelial Cells
Text Location
Results

a(CHEBI:methemoglobin) causesNoChange p(MGI:Cox4i1) View Subject | View Object

Exposure to HbFe21 and HbFe31 did not alter the expression of cytochrome c oxidase IV protein (Figure 3A). PubMed:26974230

Appears in Networks:
Annotations
MeSH
Mitochondria
Text Location
Results

a(CHEBI:methemoglobin) causesNoChange a(CHEBI:"adenosine triphosphate") View Subject | View Object

In contrast, less ATP depletion was observed during exposure to heme-albumin, and no effect could be detected when either cell type was exposed to metHb or oxyHb at concentrations of up to 500 lmolL1, even in the absence of serum. PubMed:29610666

Appears in Networks:
Annotations
Cell Ontology (CL)
neutrophil
MeSH
Human Umbilical Vein Endothelial Cells
Text Location
Results

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BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.