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Heme Curation v0.0.1-dev

Mechanistic knowledge surrounding heme

In-Edges 16

a(CHEBI:"4-hydroxynon-2-enal") negativeCorrelation p(MGI:Hp) View Subject | View Object

Hepatic 4-hydroxynonenol (4-HNE), a marker of oxidative stress, was significantly lower in the liver microsomes of SSmice 24 hours after infusion of Hp or Hpx compared to vehicle-treated SS-mice (Fig 2G). PubMed:29694434

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Liver
MeSH
Anemia, Sickle Cell
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Results

a(CHEBI:"carbon monoxide") positiveCorrelation act(p(MGI:Hp)) View Subject | View Object

The beneficial effects of Hp and Hpx were lost by inhibition of HO with SnPP, but could be restored by CO administration. PubMed:29694434

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Liver
MeSH
Anemia, Sickle Cell
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Discussion

a(MESH:"Blood Transfusion") negativeCorrelation p(MGI:Hp) View Subject | View Object

The increase in plasma haptoglobin levels from baseline to 48 hours after resuscitation was less in mice transfused with SRBCs compared to mice transfused with FRBCs (P<0.001). PubMed:27515135

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Hemorrhage
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Results

complex(a(CHEBI:"tin atom"), a(CHEBI:protoporphyrin)) negativeCorrelation act(p(MGI:Hp)) View Subject | View Object

The beneficial effects of Hp and Hpx were lost by inhibition of HO with SnPP, but could be restored by CO administration. PubMed:29694434

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Liver
MeSH
Anemia, Sickle Cell
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Discussion

complex(a(MESH:"Blood Transfusion"), p(MGI:Alb)) causesNoChange p(MGI:Hp) View Subject | View Object

Resuscitation with SRBCs together with albumin did not alter plasma levels of hemoglobin, hemopexin, haptoglobin, or heme as compared to resuscitation with SRBCs alone (Figure 3C–E, I, Supplemental Material and Supplemental Figure II A–B). PubMed:27515135

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Plasma
MeSH
Hemorrhage
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Results

act(p(MGI:Ccl5)) negativeCorrelation p(MGI:Hp) View Subject | View Object

Pro-inflammatory cytokine RANTES (chemokine ligand 5 or CCL5), which recruits leukocytes to pro-inflammatory sites, was lower in the plasma of SS-mice 24 hours after infusion of Hp or Hpx compared to vehicle-treated SS-mice (Fig 2F). PubMed:29694434

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Liver
MeSH
Anemia, Sickle Cell
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Results

p(MGI:Icam1) negativeCorrelation p(MGI:Hp) View Subject | View Object

Immunofluorescence staining of VCAM-1 and ICAM-1 was decreased in the dorsal skin of SS-mice 4h after infusion of Hb+Hp and Hb+Hpx compared to SS-mice infused with vehicle or Hb (Fig 2B and 2C). PubMed:29694434

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Liver
MeSH
Anemia, Sickle Cell
Text Location
Results

act(p(MGI:Nfkb1)) negativeCorrelation p(MGI:Hp) View Subject | View Object

Compared to Hb alone or Hb + albumin infused animals, sickle mice co-infused with Hb + Hp, Hb + Hpx, or Hb + Hp + Hpx had markedly diminished hepatic NF-κB activation 4h after infusion as evidenced by nuclear NF- κB phospho-p65 levels (Fig 2A). PubMed:29694434

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Liver
MeSH
Anemia, Sickle Cell
Text Location
Results

p(MGI:Vcam1) negativeCorrelation p(MGI:Hp) View Subject | View Object

Immunofluorescence staining of VCAM-1 and ICAM-1 was decreased in the dorsal skin of SS-mice 4h after infusion of Hb+Hp and Hb+Hpx compared to SS-mice infused with vehicle or Hb (Fig 2B and 2C). PubMed:29694434

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Liver
MeSH
Anemia, Sickle Cell
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Results

path(HM:"vaso-occlusive crisis") negativeCorrelation p(MGI:Hp) View Subject | View Object

Thus a single infusion of Hp or Hpx inhibited stasis for 48h. PubMed:29694434

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Blood Platelets
MeSH
Anemia, Sickle Cell
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Results

path(HM:"vaso-occlusive crisis") negativeCorrelation p(MGI:Hp) View Subject | View Object

Sickle mice co-infused with Hb + Hp, Hb + Hpx or Hb + Hp + Hpx had less stasis 1h after infusion than mice infused with Hb + albumin or Hb (Fig 1B). PubMed:29694434

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Blood Platelets
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Anemia, Sickle Cell
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Results

path(HM:"vaso-occlusive crisis") negativeCorrelation p(MGI:Hp) View Subject | View Object

Hp and Hpx significantly inhibited stasis in response H/R or LPS (Fig 5). PubMed:29694434

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Liver
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Anemia, Sickle Cell
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Results

path(MESH:"Porphyria, Erythropoietic") negativeCorrelation p(MGI:Hp) View Subject | View Object

Congenital erythropoietic porphyria mice showed increased serum bilirubin and LDH levels (Table 1), with almost undetectable levels of Hp and Hpx (Figure 1A and B, respectively), which was strongly indicative of hemolytic anemia. PubMed:28143953

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Cell Ontology (CL)
erythrocyte
MeSH
Serum
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Results

path(MESH:"Porphyria, Erythropoietic") negativeCorrelation p(MGI:Hp) View Subject | View Object

The Hp plasma concentration was very low in CEP mice (Figure 1A), probably because of an increased rate of its endocytosis and subsequent lysosomal degradation. PubMed:28143953

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Cell Ontology (CL)
macrophage
MeSH
Serum
MeSH
Porphyria, Erythropoietic
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Results

Out-Edges 25

p(MGI:Hp) decreases path(HM:"vaso-occlusive crisis") View Subject | View Object

These findings are consistent with a recent study which showed that both Hp and hemopexin (heme scavenger) were equally effective in preventing vasoocclusion in a sickle cell mouse model infused with Hb [73]. PubMed:24486321

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Anemia, Sickle Cell
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Discussion

p(MGI:Hp) decreases path(HM:"vaso-occlusive crisis") View Subject | View Object

Likewise, 395 infusion of haptoglobin or hemopexin in HbS mice inhibited hemoglobin-dependent 396 vaso-occlusion (3). PubMed:28314763

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Cell Ontology (CL)
endothelial cell
MeSH
Arteries
MeSH
Diabetes Mellitus
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Introduction

p(MGI:Hp) negativeCorrelation path(HM:"vaso-occlusive crisis") View Subject | View Object

Thus a single infusion of Hp or Hpx inhibited stasis for 48h. PubMed:29694434

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MeSH
Blood Platelets
MeSH
Anemia, Sickle Cell
Text Location
Results

p(MGI:Hp) negativeCorrelation path(HM:"vaso-occlusive crisis") View Subject | View Object

Sickle mice co-infused with Hb + Hp, Hb + Hpx or Hb + Hp + Hpx had less stasis 1h after infusion than mice infused with Hb + albumin or Hb (Fig 1B). PubMed:29694434

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MeSH
Blood Platelets
MeSH
Anemia, Sickle Cell
Text Location
Results

p(MGI:Hp) negativeCorrelation path(HM:"vaso-occlusive crisis") View Subject | View Object

Hp and Hpx significantly inhibited stasis in response H/R or LPS (Fig 5). PubMed:29694434

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MeSH
Liver
MeSH
Anemia, Sickle Cell
Text Location
Results

p(MGI:Hp) decreases p(MGI:Hmox1) View Subject | View Object

Hp attenuated HbFe21- and HbFe31-induced up-regulation of HO-1 and H-ferritin proteins (Figure 2B). PubMed:26974230

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Alveolar Epithelial Cells
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Results

p(MGI:Hp) decreases p(MGI:Hmox1) View Subject | View Object

Interestingly, Hp attenuated the HbFe21- and HbFe31-induced HO-1 expression in the mitochondria (Figures 3A and 3B). PubMed:26974230

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Mitochondria
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Results

p(MGI:Hp) decreases p(MGI:Fth1) View Subject | View Object

Hp attenuated HbFe21- and HbFe31-induced up-regulation of HO-1 and H-ferritin proteins (Figure 2B). PubMed:26974230

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Alveolar Epithelial Cells
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Results

p(MGI:Hp) negativeCorrelation a(MESH:"Blood Transfusion") View Subject | View Object

The increase in plasma haptoglobin levels from baseline to 48 hours after resuscitation was less in mice transfused with SRBCs compared to mice transfused with FRBCs (P<0.001). PubMed:27515135

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MeSH
Hemorrhage
Text Location
Results

p(MGI:Hp) negativeCorrelation path(MESH:"Porphyria, Erythropoietic") View Subject | View Object

Congenital erythropoietic porphyria mice showed increased serum bilirubin and LDH levels (Table 1), with almost undetectable levels of Hp and Hpx (Figure 1A and B, respectively), which was strongly indicative of hemolytic anemia. PubMed:28143953

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

p(MGI:Hp) negativeCorrelation path(MESH:"Porphyria, Erythropoietic") View Subject | View Object

The Hp plasma concentration was very low in CEP mice (Figure 1A), probably because of an increased rate of its endocytosis and subsequent lysosomal degradation. PubMed:28143953

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Annotations
Cell Ontology (CL)
macrophage
MeSH
Serum
MeSH
Porphyria, Erythropoietic
Text Location
Results

p(MGI:Hp) decreases path(MESH:"Acute Kidney Injury") View Subject | View Object

By binding cell-free hemoglobin, haptoglobin prevents glomerular filtration of cell-free hemoglobin and subsequent kidney injury (2,7). PubMed:28314763

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p(MGI:Hp) decreases bp(GO:vasoconstriction) View Subject | View Object

Schaer and colleagues 107 showed that administration of exogenous haptoglobin prevents extravasation of cell free hemoglobin and vasoconstriction in rats (18). PubMed:28314763

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p(MGI:Hp) decreases path(MESH:Hemoglobinuria) View Subject | View Object

Furthermore, haptoglobin retained cell-free 338 hemoglobin in plasma and prevented hemoglobinuria. PubMed:28314763

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Diabetes Mellitus
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Introduction

p(MGI:Hp) decreases path(MESH:Hemoglobinuria) View Subject | View Object

In mice fed a HFD or in 339 diabetic mice fed a normal diet, haptoglobin mixed with murine tetrameric 340 hemoglobin in a 1:1 weight ratio also retained cell-free hemoglobin in plasma and 341 prevented hemoglobinuria but did not reduce hemoglobin-induced hypertension. PubMed:28314763

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Diabetes Mellitus
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Introduction

p(MGI:Hp) decreases path(MESH:Hemoglobinuria) View Subject | View Object

In the 358 current study, we demonstrated that administration of human haptoglobin retained 359 cell-free hemoglobin in plasma, prevented hemoglobinuria, and reduced the 360 hemoglobin-induced hypertension in healthy awake mice (see Figure 1A). PubMed:28314763

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Arteries
MeSH
Diabetes Mellitus
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Introduction

p(MGI:Hp) decreases path(MESH:Hypertension) View Subject | View Object

Recent data suggest that haptoglobin prevents hemoglobin-induced hypertension by 355 a similar mechanism (18). PubMed:28314763

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Arteries
MeSH
Diabetes Mellitus
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Introduction

p(MGI:Hp) decreases path(MESH:Hypertension) View Subject | View Object

In the 358 current study, we demonstrated that administration of human haptoglobin retained 359 cell-free hemoglobin in plasma, prevented hemoglobinuria, and reduced the 360 hemoglobin-induced hypertension in healthy awake mice (see Figure 1A). PubMed:28314763

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MeSH
Arteries
MeSH
Diabetes Mellitus
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Introduction

p(MGI:Hp) negativeCorrelation act(p(MGI:Nfkb1)) View Subject | View Object

Compared to Hb alone or Hb + albumin infused animals, sickle mice co-infused with Hb + Hp, Hb + Hpx, or Hb + Hp + Hpx had markedly diminished hepatic NF-κB activation 4h after infusion as evidenced by nuclear NF- κB phospho-p65 levels (Fig 2A). PubMed:29694434

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Annotations
MeSH
Liver
MeSH
Anemia, Sickle Cell
Text Location
Results

p(MGI:Hp) negativeCorrelation p(MGI:Vcam1) View Subject | View Object

Immunofluorescence staining of VCAM-1 and ICAM-1 was decreased in the dorsal skin of SS-mice 4h after infusion of Hb+Hp and Hb+Hpx compared to SS-mice infused with vehicle or Hb (Fig 2B and 2C). PubMed:29694434

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MeSH
Liver
MeSH
Anemia, Sickle Cell
Text Location
Results

p(MGI:Hp) negativeCorrelation p(MGI:Icam1) View Subject | View Object

Immunofluorescence staining of VCAM-1 and ICAM-1 was decreased in the dorsal skin of SS-mice 4h after infusion of Hb+Hp and Hb+Hpx compared to SS-mice infused with vehicle or Hb (Fig 2B and 2C). PubMed:29694434

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MeSH
Liver
MeSH
Anemia, Sickle Cell
Text Location
Results

p(MGI:Hp) negativeCorrelation act(p(MGI:Ccl5)) View Subject | View Object

Pro-inflammatory cytokine RANTES (chemokine ligand 5 or CCL5), which recruits leukocytes to pro-inflammatory sites, was lower in the plasma of SS-mice 24 hours after infusion of Hp or Hpx compared to vehicle-treated SS-mice (Fig 2F). PubMed:29694434

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Annotations
MeSH
Liver
MeSH
Anemia, Sickle Cell
Text Location
Results

p(MGI:Hp) negativeCorrelation a(CHEBI:"4-hydroxynon-2-enal") View Subject | View Object

Hepatic 4-hydroxynonenol (4-HNE), a marker of oxidative stress, was significantly lower in the liver microsomes of SSmice 24 hours after infusion of Hp or Hpx compared to vehicle-treated SS-mice (Fig 2G). PubMed:29694434

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Annotations
MeSH
Liver
MeSH
Anemia, Sickle Cell
Text Location
Results

act(p(MGI:Hp)) negativeCorrelation complex(a(CHEBI:"tin atom"), a(CHEBI:protoporphyrin)) View Subject | View Object

The beneficial effects of Hp and Hpx were lost by inhibition of HO with SnPP, but could be restored by CO administration. PubMed:29694434

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MeSH
Liver
MeSH
Anemia, Sickle Cell
Text Location
Discussion

act(p(MGI:Hp)) positiveCorrelation a(CHEBI:"carbon monoxide") View Subject | View Object

The beneficial effects of Hp and Hpx were lost by inhibition of HO with SnPP, but could be restored by CO administration. PubMed:29694434

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MeSH
Liver
MeSH
Anemia, Sickle Cell
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.