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p(MGI:Slc40a1)

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Entity

Name
Slc40a1
Namespace
mgi
Namespace Version
20181021
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/f2f993e599694ab5ce989cc39d789a499f75db99/external/mgi-names.belns

Appears in Networks 1

Heme Curation v0.0.1-dev

Mechanistic knowledge surrounding heme

In-Edges 23

a(CHEBI:"desferrioxamine B") decreases p(MGI:Slc40a1) View Subject | View Object

Expectedly, and in line with previous report (13), treatment of macrophages with DFO abolished ferroportin and ferritin induction by heme, whereas TfR1 expression was lowered upon heme and combined treatment with heme and DFO (Fig. 7D). PubMed:29212341

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Cell Ontology (CL)
macrophage
Text Location
Results

a(CHEBI:"iron(2+)") positiveCorrelation p(MGI:Slc40a1) View Subject | View Object

These data suggested that during severe hemolysis, heme mediated ferroportin induction and low hepcidin in HbS mice (11) served to elevate systemic iron availability, required to sustain high erythropoietic demands in these mice. PubMed:29212341

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Cell Ontology (CL)
macrophage
Text Location
Results

a(CHEBI:acetylcysteine) decreases p(MGI:Slc40a1) View Subject | View Object

We showed that NAC treatment scavenged ROS production and, more importantly, it counteracted ferroportin induction by heme (Fig. 8B, C). PubMed:29212341

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Cell Ontology (CL)
macrophage
Text Location
Results

a(CHEBI:heme) increases p(MGI:Slc40a1) View Subject | View Object

Heme induced the expression of Ho1 and Blvrb as well as Slc40a1, which encodes the mammalian iron exporter (Figure 5A), in agreement with previous reports (Delaby et al., 2008). PubMed:24630724

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Text Location
Results

a(CHEBI:heme) positiveCorrelation p(MGI:Slc40a1) View Subject | View Object

High ferroportin levels were measured in macrophages upon heme overload and erythrophagocytosis (12, 13, 31, 32, 37) and in hemolytic murine models of b-thalassemia and phenylhydrazineinduced hemolytic anemia (11, 22, 34). PubMed:29212341

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
Text Location
Introduction

a(CHEBI:heme) positiveCorrelation p(MGI:Slc40a1) View Subject | View Object

These data suggested that during severe hemolysis, heme mediated ferroportin induction and low hepcidin in HbS mice (11) served to elevate systemic iron availability, required to sustain high erythropoietic demands in these mice. PubMed:29212341

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

a(CHEBI:heme) positiveCorrelation p(MGI:Slc40a1) View Subject | View Object

Our in vivo observations could be recapitulated in isolated macrophages, which upon stimulation with heme (25 lM; 16 h) demonstrated increased ferroportin mRNA and protein expression (Fig. 4A, B) and a significant decrease in the intracellular iron pool (2.2-fold; p < 0.01) (Fig. 4C). PubMed:29212341

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

a(CHEBI:heme) positiveCorrelation p(MGI:Slc40a1) View Subject | View Object

So far, our results established that in the conditions of acute and chronic heme overload, macrophages acquired high ferroportin expression and an efficient iron export. PubMed:29212341

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

a(CHEBI:heme) positiveCorrelation p(MGI:Slc40a1) View Subject | View Object

Under heme overload conditions, macrophages acquire an iron phenotype characterized by low intracellular iron and high ferroportin expression. PubMed:29212341

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Cell Ontology (CL)
macrophage
Text Location
Discussion

a(CHEBI:lipopolysaccharide) negativeCorrelation p(MGI:Slc40a1) View Subject | View Object

We showed that simulation of macrophages with LPS resulted in significant reduction in ferroportin mRNA and protein expression and enhanced intracellular iron deposition throughout all time points tested (Fig. 5A–D). PubMed:29212341

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Cell Ontology (CL)
macrophage
Text Location
Results

a(CHEBI:lipopolysaccharide) negativeCorrelation p(MGI:Slc40a1) View Subject | View Object

This dramatically contrasts the iron phenotype that develops in response to LPS, hallmarked by high intracellular iron levels and low ferroportin expression (10, 20, 48). PubMed:29212341

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Cell Ontology (CL)
macrophage
Text Location
Discussion

a(CHEBI:protoporphyrin) causesNoChange p(MGI:Slc40a1) View Subject | View Object

By contrast, treatment of macrophages with PPIX failed to increase the ROS production and ferroportin expression, implying that iron within the heme moiety was required for the observed effects (Fig. 7B). PubMed:29212341

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Annotations
Cell Ontology (CL)
macrophage
Text Location
Results

a(HM:erythrophagocytosis) positiveCorrelation p(MGI:Slc40a1) View Subject | View Object

High ferroportin levels were measured in macrophages upon heme overload and erythrophagocytosis (12, 13, 31, 32, 37) and in hemolytic murine models of b-thalassemia and phenylhydrazineinduced hemolytic anemia (11, 22, 34). PubMed:29212341

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
Text Location
Introduction

act(a(MESH:"NADPH Oxidase")) positiveCorrelation p(MGI:Slc40a1) View Subject | View Object

Our study provides evidence that the increase in cellular oxidant levels, as a result of NADPH oxidase activity, was responsible for ferroportin induction by heme. PubMed:29212341

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

a(MESH:"Reactive Oxygen Species") increases p(MGI:Slc40a1) View Subject | View Object

We show that heme, in a concentration range found during hemolytic episodes, increases intracellular ROS production and consequentially signals for ferroportin induction and subsequent iron export from the macrophages. PubMed:29212341

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Annotations
Cell Ontology (CL)
macrophage
Text Location
Discussion

complex(a(CHEBI:acetylcysteine), a(CHEBI:heme)) decreases p(MGI:Slc40a1) View Subject | View Object

We showed that increase in ferroportin mRNA and protein expression by heme was effectively prevented in mice receiving combined treatment of NAC and heme (Fig. 8D, E). PubMed:29212341

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

complex(a(CHEBI:allopurinol), a(CHEBI:heme)) decreases p(MGI:Slc40a1) View Subject | View Object

We showed that cotreatment of macrophages with heme and apocynin (Fig. 7E), as well as with heme and allopurinol (Fig. 7F), fully prevented ferroportin induction by heme. These data revealed that inhibiting superoxide at its production site is an effective way to counteract heme-mediated ferroportin induction. PubMed:29212341

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

complex(a(CHEBI:apocynin), a(CHEBI:heme)) decreases p(MGI:Slc40a1) View Subject | View Object

We showed that cotreatment of macrophages with heme and apocynin (Fig. 7E), as well as with heme and allopurinol (Fig. 7F), fully prevented ferroportin induction by heme. These data revealed that inhibiting superoxide at its production site is an effective way to counteract heme-mediated ferroportin induction. PubMed:29212341

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

p(MGI:Hpx) decreases p(MGI:Slc40a1) View Subject | View Object

Moreover, in CMs the heme-mediated induction of the iron exporter Ferroportin (Fpn) was abrogated by Hx treatment while the down-regulation of the iron importer Transferrin receptor 1 (TfR1) was significantly reduced by Hx (see Figure 3 in [37]) further indicating that Hx limits heme-iron accumulation within the cell. PubMed:28400318

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Cell Ontology (CL)
regular cardiac myocyte
Text Location
Results

complex(p(MGI:Hamp), p(MGI:Slc40a1)) hasComponent p(MGI:Slc40a1) View Subject | View Object

Appears in Networks:

complex(p(MGI:Hamp), p(MGI:Slc40a1)) increases deg(p(MGI:Slc40a1)) View Subject | View Object

In addition, ferroportin undergoes post-translational control by the systemic iron regulator, hepcidin, whereby binding of hepcidin to ferroportin causes its internalization and degradation, leading to iron retention within the cells (21, 41). PubMed:29212341

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
Text Location
Introduction

path(MESH:"Porphyria, Erythropoietic") positiveCorrelation p(MGI:Slc40a1) View Subject | View Object

In addition, we observed an increase of ferroportin protein expression in duodenal enterocytes (Figure 3E and F). PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
bone marrow cell
MeSH
Duodenum
MeSH
Porphyria, Erythropoietic
Text Location
Results

path(MESH:"Porphyria, Erythropoietic") positiveCorrelation p(MGI:Slc40a1) View Subject | View Object

In addition, despite an increase in ferritin expression, ferroportin expression was also induced in the liver of CEP mice (Figure 4E), suggesting an increase of iron release in the circulation to satisfy the high iron demand. PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Porphyria, Erythropoietic
Text Location
Results

Out-Edges 12

p(MGI:Slc40a1) positiveCorrelation path(MESH:"Porphyria, Erythropoietic") View Subject | View Object

In addition, we observed an increase of ferroportin protein expression in duodenal enterocytes (Figure 3E and F). PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
bone marrow cell
MeSH
Duodenum
MeSH
Porphyria, Erythropoietic
Text Location
Results

p(MGI:Slc40a1) positiveCorrelation path(MESH:"Porphyria, Erythropoietic") View Subject | View Object

In addition, despite an increase in ferritin expression, ferroportin expression was also induced in the liver of CEP mice (Figure 4E), suggesting an increase of iron release in the circulation to satisfy the high iron demand. PubMed:28143953

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Porphyria, Erythropoietic
Text Location
Results

p(MGI:Slc40a1) positiveCorrelation a(CHEBI:heme) View Subject | View Object

High ferroportin levels were measured in macrophages upon heme overload and erythrophagocytosis (12, 13, 31, 32, 37) and in hemolytic murine models of b-thalassemia and phenylhydrazineinduced hemolytic anemia (11, 22, 34). PubMed:29212341

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
Text Location
Introduction

p(MGI:Slc40a1) positiveCorrelation a(CHEBI:heme) View Subject | View Object

These data suggested that during severe hemolysis, heme mediated ferroportin induction and low hepcidin in HbS mice (11) served to elevate systemic iron availability, required to sustain high erythropoietic demands in these mice. PubMed:29212341

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

p(MGI:Slc40a1) positiveCorrelation a(CHEBI:heme) View Subject | View Object

Our in vivo observations could be recapitulated in isolated macrophages, which upon stimulation with heme (25 lM; 16 h) demonstrated increased ferroportin mRNA and protein expression (Fig. 4A, B) and a significant decrease in the intracellular iron pool (2.2-fold; p < 0.01) (Fig. 4C). PubMed:29212341

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

p(MGI:Slc40a1) positiveCorrelation a(CHEBI:heme) View Subject | View Object

So far, our results established that in the conditions of acute and chronic heme overload, macrophages acquired high ferroportin expression and an efficient iron export. PubMed:29212341

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

p(MGI:Slc40a1) positiveCorrelation a(CHEBI:heme) View Subject | View Object

Under heme overload conditions, macrophages acquire an iron phenotype characterized by low intracellular iron and high ferroportin expression. PubMed:29212341

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

p(MGI:Slc40a1) positiveCorrelation a(HM:erythrophagocytosis) View Subject | View Object

High ferroportin levels were measured in macrophages upon heme overload and erythrophagocytosis (12, 13, 31, 32, 37) and in hemolytic murine models of b-thalassemia and phenylhydrazineinduced hemolytic anemia (11, 22, 34). PubMed:29212341

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
Text Location
Introduction

p(MGI:Slc40a1) positiveCorrelation a(CHEBI:"iron(2+)") View Subject | View Object

These data suggested that during severe hemolysis, heme mediated ferroportin induction and low hepcidin in HbS mice (11) served to elevate systemic iron availability, required to sustain high erythropoietic demands in these mice. PubMed:29212341

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

p(MGI:Slc40a1) negativeCorrelation a(CHEBI:lipopolysaccharide) View Subject | View Object

We showed that simulation of macrophages with LPS resulted in significant reduction in ferroportin mRNA and protein expression and enhanced intracellular iron deposition throughout all time points tested (Fig. 5A–D). PubMed:29212341

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

p(MGI:Slc40a1) negativeCorrelation a(CHEBI:lipopolysaccharide) View Subject | View Object

This dramatically contrasts the iron phenotype that develops in response to LPS, hallmarked by high intracellular iron levels and low ferroportin expression (10, 20, 48). PubMed:29212341

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

p(MGI:Slc40a1) positiveCorrelation act(a(MESH:"NADPH Oxidase")) View Subject | View Object

Our study provides evidence that the increase in cellular oxidant levels, as a result of NADPH oxidase activity, was responsible for ferroportin induction by heme. PubMed:29212341

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

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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.