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p(HGNC:HPX)

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Entity

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

Appears in Networks 1

Heme Curation v0.0.1-dev

Mechanistic knowledge surrounding heme

In-Edges 13

a(CHEBI:ATP) positiveCorrelation p(HGNC:HPX) View Subject | View Object

This ATP depletion was prevented by the addition of the heme scavenger, hemopexin (Figure 5b). PubMed:26794659

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

bp(HM:"macrophage M1 polarization") negativeCorrelation p(HGNC:HPX) View Subject | View Object

Treatment with Hx or DFO diminished the increase of some M1 polarization markers in BMDMs following treatment with hemolytic RBCs (supplemental Figure 14). PubMed:26675351

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

bp(MESH:"Blood Pressure") negativeCorrelation p(HGNC:HPX) View Subject | View Object

Correlation analysis using Pearson’s correlation coefficient showed statistically significant inverse correlation between Hpx and blood pressure, both systolic (r = -0.511, pvalue< 0.00001, n = 145) and diastolic (r = -0,520, p-value<0.00001, n = 145)(Fig 3). PubMed:26368565

Appears in Networks:
Annotations
Cell Ontology (CL)
hepatocyte
MeSH
Plasma
MeSH
Pre-Eclampsia
Text Location
Results

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

p(HGNC:ARG1) positiveCorrelation p(HGNC:HPX) View Subject | View Object

In addition, Hx and DFO prevented the heme- and ironmediated induction of the M1 markers MHCII, CD86, CD14, and TNFα and the decrease of some M2 markers, such as CD206, IL-10, and Arginase-1 (the last for FeNTA only) in M0 BMDMs (Figure 6A; supplemental Figure 15A). PubMed:26675351

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

p(HGNC:IL10) positiveCorrelation p(HGNC:HPX) View Subject | View Object

In addition, Hx and DFO prevented the heme- and ironmediated induction of the M1 markers MHCII, CD86, CD14, and TNFα and the decrease of some M2 markers, such as CD206, IL-10, and Arginase-1 (the last for FeNTA only) in M0 BMDMs (Figure 6A; supplemental Figure 15A). PubMed:26675351

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

p(HGNC:MRC1) positiveCorrelation p(HGNC:HPX) View Subject | View Object

In addition, Hx and DFO prevented the heme- and ironmediated induction of the M1 markers MHCII, CD86, CD14, and TNFα and the decrease of some M2 markers, such as CD206, IL-10, and Arginase-1 (the last for FeNTA only) in M0 BMDMs (Figure 6A; supplemental Figure 15A). PubMed:26675351

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

path(MESH:"Anemia, Sickle Cell") negativeCorrelation p(HGNC:HPX) View Subject | View Object

Studies of sickle cell anemia patients have reported decreased levels of Hpx following hemolysis [68]. PubMed:26368565

Appears in Networks:
Annotations
Cell Ontology (CL)
hepatocyte
MeSH
Plasma
MeSH
Pre-Eclampsia
Text Location
Discussion

path(MESH:"Pre-Eclampsia") negativeCorrelation p(HGNC:HPX) View Subject | View Object

Analysis of the intravascular heme-scavenger protein Hpx showed a statistically significant decrease in plasma Hpx concentration of women with PE (p-value<0.0001) as compared to the controls (Table 3). PubMed:26368565

Appears in Networks:
Annotations
Cell Ontology (CL)
hepatocyte
MeSH
Plasma
MeSH
Pre-Eclampsia
Text Location
Results

path(MESH:Hemolysis) negativeCorrelation p(HGNC:HPX) View Subject | View Object

In cases of extensive and chronic hemolysis, levels of haptoglobin and hemopexin in plasma decrease markedly [20,21]. PubMed:26875449

Appears in Networks:
Annotations
Text Location
Review

path(MESH:Hemolysis) negativeCorrelation p(HGNC:HPX) View Subject | View Object

Plasma haptoglobin and hemopexin levels are often depleted in SCD patients and mice due to chronic intravascular hemolysis [21±24]. PubMed:29694434

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

Out-Edges 34

p(HGNC:HPX) decreases a(HM:"oxidative modification of atheroma lipid") View Subject | View Object

Moreover, the heme-binding protein, hemopexin, also suppressed the oxidation of lipid by ferro- and ferrihemoglobin, indicating the necessity for heme release from ferrihemoglobin for this oxidative process. PubMed:20378845

Appears in Networks:
Annotations
Cell Ontology (CL)
endothelial cell
MeSH
Plaque, Atherosclerotic
Text Location
Results

p(HGNC:HPX) decreases a(HM:"oxidative modification of atheroma lipid") View Subject | View Object

Both the hemoglobin-binding protein, haptoglobin,27 and the heme-binding protein, hemopexin, inhibited such oxidative modification of lipids indicating the importance of heme loss and scission in hemoglobin-provoked oxidation of lipids derived from atheromatous lesions. PubMed:20378845

Appears in Networks:
Annotations
Cell Ontology (CL)
endothelial cell
MeSH
Atherosclerosis
Text Location
Discussion

p(HGNC:HPX) decreases bp(MESH:"Lipid Peroxidation") View Subject | View Object

Inhibition of lipid oxidation by either haptoglobin or hemopexin reduced the cytotoxicity (Fig 4B) and HO-1 induction caused by sublethal amounts of pretreated atheromatous lesion lipids (Fig 4C and D). PubMed:20378845

Appears in Networks:
Annotations
Cell Ontology (CL)
endothelial cell
MeSH
Plaque, Atherosclerotic
Text Location
Results

p(HGNC:HPX) decreases a(HM:"oxidative reactions") View Subject | View Object

The heme-binding protein, hemopexin, which likely prevents heme:lipid interactions and blocks the oxidative scission of heme,26 significantly inhibited the oxidative reactions. PubMed:20378845

Appears in Networks:
Annotations
Cell Ontology (CL)
endothelial cell
MeSH
Atherosclerosis
Text Location
Discussion

p(HGNC:HPX) decreases path(HM:"Endothelial dysfunction") View Subject | View Object

We have found that atheroma lipids when oxidized by heme are highly cytotoxic to human endothelial cells, and hemopexin reduced this cytotoxicity. PubMed:20378845

Appears in Networks:
Annotations
Cell Ontology (CL)
endothelial cell
MeSH
Atherosclerosis
Text Location
Discussion

p(HGNC:HPX) decreases a(CHEBI:heme) View Subject | View Object

Importantly, heme b interaction with heme oxygenase (HO; Lad et al., 2003), the enzyme responsible for heme intracellular catabolism, and hemopexin (Hx; Paoli et al., 1999), a plasmatic heme scavenger, is essential for the regulation of free heme availability and Fe recycling (Kovtunovych et al., 2010; Tolosano et al., 2010). PubMed:24904418

Appears in Networks:
Annotations
Text Location
Review

p(HGNC:HPX) decreases a(CHEBI:heme) View Subject | View Object

Based on clinical observations the Hb and heme scavenger proteins haptoglobin (Hp) and hemopexin (Hx) have been characterized as a sequential defense system with Hp as the primary protector and Hx as a backup when all Hp is depleted during more severe intravascular hemolysis. PubMed:26475040

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

p(HGNC:HPX) decreases a(CHEBI:heme) View Subject | View Object

Recently, we demonstrated that Hx controls hepatic heme uptake and thus limits heme accumulation in extrahepatic tissues, such as the vessel wall and the heart, preventing heme-induced toxicity and tissue injury. PubMed:26675351

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

p(HGNC:HPX) decreases a(CHEBI:heme) View Subject | View Object

Taken together, these data demonstrate that Hx limits macrophage heme overload and prevents the prooxidant and proinflammatory effects triggered by heme in cellular assays and in vivo. PubMed:26675351

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

p(HGNC:HPX) decreases a(CHEBI:heme) View Subject | View Object

Thus, the interactions of hemoglobin with haptoglobin, and of heme with hemopexin, ensure safe disposal of potentially dangerous molecules [6,7,15–19] PubMed:26875449

Appears in Networks:
Annotations
Text Location
Review

p(HGNC:HPX) decreases a(CHEBI:heme) View Subject | View Object

Heme released from cell-free hemoglobin on oxidation is bound by hemopexin and degraded by hepatocytes in the liver [12]. PubMed:29956069

Appears in Networks:
Annotations
Cell Ontology (CL)
hepatocyte
MeSH
Liver
MeSH
Sepsis
Text Location
Review

p(HGNC:HPX) decreases a(CHEBI:heme) View Subject | View Object

Of the biological components known to bind hemin, Hpx is by far the most efficient with a dissociation constant (Kd) lower than 1 x 10–13 M; as a result, after binding, the transfer of hemin from Hpx to other proteins or lipids is not possible [24]. PubMed:30281034

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Anemia, Sickle Cell
MeSH
beta-Thalassemia
Text Location
Review

p(HGNC:HPX) decreases a(CHEBI:heme) View Subject | View Object

On the extracellular level, within the circulation, haptoglobin (Hp) and hemopexin (Hpx) are two of the most prominent scavenger proteins, with antioxidative properties through their capacity to remove cell-free Hb (by Hp) and heme (by Hpx). PubMed:30505280

Appears in Networks:
Annotations
MeSH
Knee
MeSH
Osteoarthritis, Knee
Text Location
Introduction

p(HGNC:HPX) decreases bp(GO:"heme oxidation") View Subject | View Object

Hx inhibits the oxidative property of heme (Eskew et al., 1999) and mediates heme transportation to intracellular compartments through the macrophage receptor CD91 (Hvidberg et al., 2005), a critical step on heme catabolism. PubMed:24904418

Appears in Networks:
Annotations
Text Location
Review

p(HGNC:HPX) decreases path(MESH:Inflammation) View Subject | View Object

In fact, hemolysis or heme injection in Hx−/− mice cause increased inflammation and severe renal damage compared to wild type (WT) mice (Tolosano et al., 1999; Vinchi et al., 2008). PubMed:24904418

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

p(HGNC:HPX) decreases path(MESH:"Kidney Diseases") View Subject | View Object

In fact, hemolysis or heme injection in Hx−/− mice cause increased inflammation and severe renal damage compared to wild type (WT) mice (Tolosano et al., 1999; Vinchi et al., 2008). PubMed:24904418

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

p(HGNC:HPX) negativeCorrelation path(MESH:"Pre-Eclampsia") View Subject | View Object

Analysis of the intravascular heme-scavenger protein Hpx showed a statistically significant decrease in plasma Hpx concentration of women with PE (p-value<0.0001) as compared to the controls (Table 3). PubMed:26368565

Appears in Networks:
Annotations
Cell Ontology (CL)
hepatocyte
MeSH
Plasma
MeSH
Pre-Eclampsia
Text Location
Results

p(HGNC:HPX) negativeCorrelation bp(MESH:"Blood Pressure") View Subject | View Object

Correlation analysis using Pearson’s correlation coefficient showed statistically significant inverse correlation between Hpx and blood pressure, both systolic (r = -0.511, pvalue< 0.00001, n = 145) and diastolic (r = -0,520, p-value<0.00001, n = 145)(Fig 3). PubMed:26368565

Appears in Networks:
Annotations
Cell Ontology (CL)
hepatocyte
MeSH
Plasma
MeSH
Pre-Eclampsia
Text Location
Results

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

However, no changes in peroxidase activity were observed after incubation with haptoglobin or hemopexin (Fig. 2). PubMed:28088643

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

p(HGNC:HPX) negativeCorrelation path(MESH:"Anemia, Sickle Cell") View Subject | View Object

Studies of sickle cell anemia patients have reported decreased levels of Hpx following hemolysis [68]. PubMed:26368565

Appears in Networks:
Annotations
Cell Ontology (CL)
hepatocyte
MeSH
Plasma
MeSH
Pre-Eclampsia
Text Location
Discussion

p(HGNC:HPX) decreases a(MESH:"Reactive Oxygen Species") View Subject | View Object

Taken together, these data demonstrate that Hx limits macrophage heme overload and prevents the prooxidant and proinflammatory effects triggered by heme in cellular assays and in vivo. PubMed:26675351

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

p(HGNC:HPX) decreases bp(GO:"inflammatory response") View Subject | View Object

Taken together, these data demonstrate that Hx limits macrophage heme overload and prevents the prooxidant and proinflammatory effects triggered by heme in cellular assays and in vivo. PubMed:26675351

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

p(HGNC:HPX) negativeCorrelation bp(HM:"macrophage M1 polarization") View Subject | View Object

Treatment with Hx or DFO diminished the increase of some M1 polarization markers in BMDMs following treatment with hemolytic RBCs (supplemental Figure 14). PubMed:26675351

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

p(HGNC:HPX) decreases complex(SCOMP:"MHC Class II Complex") View Subject | View Object

In addition, Hx and DFO prevented the heme- and ironmediated induction of the M1 markers MHCII, CD86, CD14, and TNFα and the decrease of some M2 markers, such as CD206, IL-10, and Arginase-1 (the last for FeNTA only) in M0 BMDMs (Figure 6A; supplemental Figure 15A). PubMed:26675351

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

p(HGNC:HPX) decreases p(HGNC:CD86) View Subject | View Object

In addition, Hx and DFO prevented the heme- and ironmediated induction of the M1 markers MHCII, CD86, CD14, and TNFα and the decrease of some M2 markers, such as CD206, IL-10, and Arginase-1 (the last for FeNTA only) in M0 BMDMs (Figure 6A; supplemental Figure 15A). PubMed:26675351

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

p(HGNC:HPX) negativeCorrelation path(MESH:Hemolysis) View Subject | View Object

Plasma haptoglobin and hemopexin levels are often depleted in SCD patients and mice due to chronic intravascular hemolysis [21±24]. PubMed:29694434

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

p(HGNC:HPX) decreases p(HGNC:CD14) View Subject | View Object

In addition, Hx and DFO prevented the heme- and ironmediated induction of the M1 markers MHCII, CD86, CD14, and TNFα and the decrease of some M2 markers, such as CD206, IL-10, and Arginase-1 (the last for FeNTA only) in M0 BMDMs (Figure 6A; supplemental Figure 15A). PubMed:26675351

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

p(HGNC:HPX) decreases p(HGNC:TNF) View Subject | View Object

In addition, Hx and DFO prevented the heme- and ironmediated induction of the M1 markers MHCII, CD86, CD14, and TNFα and the decrease of some M2 markers, such as CD206, IL-10, and Arginase-1 (the last for FeNTA only) in M0 BMDMs (Figure 6A; supplemental Figure 15A). PubMed:26675351

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

p(HGNC:HPX) positiveCorrelation p(HGNC:MRC1) View Subject | View Object

In addition, Hx and DFO prevented the heme- and ironmediated induction of the M1 markers MHCII, CD86, CD14, and TNFα and the decrease of some M2 markers, such as CD206, IL-10, and Arginase-1 (the last for FeNTA only) in M0 BMDMs (Figure 6A; supplemental Figure 15A). PubMed:26675351

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

p(HGNC:HPX) positiveCorrelation p(HGNC:ARG1) View Subject | View Object

In addition, Hx and DFO prevented the heme- and ironmediated induction of the M1 markers MHCII, CD86, CD14, and TNFα and the decrease of some M2 markers, such as CD206, IL-10, and Arginase-1 (the last for FeNTA only) in M0 BMDMs (Figure 6A; supplemental Figure 15A). PubMed:26675351

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

p(HGNC:HPX) positiveCorrelation p(HGNC:IL10) View Subject | View Object

In addition, Hx and DFO prevented the heme- and ironmediated induction of the M1 markers MHCII, CD86, CD14, and TNFα and the decrease of some M2 markers, such as CD206, IL-10, and Arginase-1 (the last for FeNTA only) in M0 BMDMs (Figure 6A; supplemental Figure 15A). PubMed:26675351

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

p(HGNC:HPX) positiveCorrelation a(CHEBI:ATP) View Subject | View Object

This ATP depletion was prevented by the addition of the heme scavenger, hemopexin (Figure 5b). PubMed:26794659

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

p(HGNC:HPX) negativeCorrelation path(MESH:Hemolysis) View Subject | View Object

In cases of extensive and chronic hemolysis, levels of haptoglobin and hemopexin in plasma decrease markedly [20,21]. PubMed:26875449

Appears in Networks:
Annotations
Text Location
Review

p(HGNC:HPX) decreases path(HM:"microvascular stasis") View Subject | View Object

Vinchi and co-workers proved that the hemoglobin scavenger hemopexin prevents from hepatic microvascular stasis induced by intravascular hemolysis (using a mouse model of heme overloadin wild-typemicecomparedtohemopexin-nullmice) [116]. PubMed:29956069

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Liver
MeSH
Disseminated Intravascular Coagulation
Text Location
Review

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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.