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  3. PubMed:24904418

PubMed: 24904418

Title
Heme on innate immunity and inflammation.
Journal
Frontiers in pharmacology
Volume
5
Issue
None
Pages
115
Date
2014-01-01
Authors
Bozza MT | Dutra FF

Evidence a51adf7c4f
JSON

Furthermore, heme induces ROS generation dependent on enzymatic reactions.

a(CHEBI:heme) increases a(MESH:"Reactive Oxygen Species") View Subject | View Object

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

Evidence 9804c1bdc0
JSON

Heme induces ROS generation independently of TLR4.

a(CHEBI:heme) increases a(MESH:"Reactive Oxygen Species") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

Evidence aa56fbd3fb
JSON

Heme activates neutrophils and endothelial cells, by ROS generation.

a(CHEBI:heme) increases a(MESH:"Reactive Oxygen Species") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

a(MESH:"Reactive Oxygen Species") increases bp(GO:"endothelial cell activation") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

a(MESH:"Reactive Oxygen Species") increases bp(MESH:"Neutrophil Activation") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

Evidence 1f7a8628b6
JSON

Differently from biliverdin and CO, which have anti-inflammatory effects (Otterbein et al., 2000; Baranano et al., 2002), free Fe is highly oxidative and can promote free radicals generation through the Fenton reaction, which catalyzes hydroxyl radicals from the reaction of Fe with H2O2 (Fenton, 1894).

a(CHEBI:"carbon monoxide") decreases bp(GO:"inflammatory response") View Subject | View Object

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a(CHEBI:"iron(2+)") positiveCorrelation a(MESH:"Free Radicals") View Subject | View Object

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a(MESH:"Free Radicals") positiveCorrelation a(CHEBI:"iron(2+)") View Subject | View Object

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a(MESH:Biliverdine) decreases bp(GO:"inflammatory response") View Subject | View Object

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Review

Evidence 617bc38603
JSON

Heme also induces the expression of the adhesion molecules ICAM-1, VCAM-1, and E-selectins.

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

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

a(CHEBI:heme) increases p(HGNC:ICAM1) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

a(CHEBI:heme) increases p(HGNC:VCAM1) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

Evidence b54040e125
JSON

CO inhibits Hb oxidation and subsequently heme release, thus blocking heme accumulation in serum and preventing heme from exerting its inflammatory effects in the course of malaria disease (Ferreira et al., 2011).

a(CHEBI:"carbon monoxide") decreases a(CHEBI:heme) View Subject | View Object

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

a(CHEBI:heme) increases path(MESH:Inflammation) View Subject | View Object

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

Evidence b7865d6247
JSON

Besides its physiological importance, heme has a potent oxidative capacity oxidizing lipids (Tappel, 1953, 1955; Vincent et al., 1988) and proteins (Aft and Mueller, 1984; Vincent, 1989), and damaging DNA (Aft and Mueller, 1983).

a(CHEBI:"deoxyribonucleic acid") negativeCorrelation a(CHEBI:heme) View Subject | View Object

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a(CHEBI:heme) positiveCorrelation bp(MESH:"Lipid Peroxidation") View Subject | View Object

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Review

a(CHEBI:heme) positiveCorrelation bp(GO:"protein oxidation") View Subject | View Object

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Text Location
Review

a(CHEBI:heme) negativeCorrelation a(CHEBI:"deoxyribonucleic acid") View Subject | View Object

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Text Location
Review

bp(GO:"protein oxidation") positiveCorrelation a(CHEBI:heme) View Subject | View Object

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Text Location
Review

bp(MESH:"Lipid Peroxidation") positiveCorrelation a(CHEBI:heme) View Subject | View Object

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Text Location
Review

Evidence f13172c282
JSON

Heme-induced necroptosis is reversed by deferoxamine, a Fe chelator.

a(CHEBI:"desferrioxamine B") negativeCorrelation bp(GO:"necroptotic process") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

bp(GO:"necroptotic process") negativeCorrelation a(CHEBI:"desferrioxamine B") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

Evidence 1483ab0c31
JSON

Once intercalated into cellular plasma membranes heme amplifies cellular susceptibility to oxidative-mediated injury by oxidants such as H2O2 or those derived from activated inflammatory cells (Balla et al., 1991a,b, 1993).

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

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

a(CHEBI:heme) increases a(CHEBI:hydroperoxide) View Subject | View Object

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

Evidence 835c429aa4
JSON

These concepts challenged the idea that the cytotoxic and inflammatory effects of heme were exclusively mediated by the oxidative capability of the Fe associated with the amphipathic property of the porphyrin ring.

a(CHEBI:"iron(2+)") increases path(MESH:Inflammation) View Subject | View Object

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

Evidence 100d76b39b
JSON

In fact, heme can induce neutrophil migration by acting as a chemotactic molecule (Porto et al., 2007) or by inducing the production of leukotriene B4 (LTB4) by macrophages (Monteiro et al., 2011).

a(CHEBI:"leukotriene B4") increases bp(GO:"neutrophil migration") View Subject | View Object

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

Evidence 397d6c52f2
JSON

As described before, LTB4 has an important function regulating heme-induced neutrophils migration (Monteiro et al., 2011).

a(CHEBI:"leukotriene B4") increases bp(GO:"neutrophil migration") View Subject | View Object

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

a(CHEBI:heme) increases bp(GO:"neutrophil migration") View Subject | View Object

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

Evidence 9240a50013
JSON

KC (keratinocyte-derived chemokine) is a chemokine that attracts neutrophils to sites of inflammation and LTB4 is a lipid mediator that functions as a chemoattractant molecule and also activates leukocytes.

a(CHEBI:"leukotriene B4") increases act(a(MESH:Leukocytes)) View Subject | View Object

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

Evidence 9e5837ce24
JSON

Low-density lipoprotein is the major lipid involved in plaque formation.

a(CHEBI:"low-density lipoprotein") positiveCorrelation path(MESH:"Plaque, Atherosclerotic") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Cerebral Hemorrhage
Text Location
Review

path(MESH:"Plaque, Atherosclerotic") positiveCorrelation a(CHEBI:"low-density lipoprotein") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Cerebral Hemorrhage
Text Location
Review

Evidence 566745a966
JSON

In fact, heme-induced LDL oxidation is highly cytotoxic for endothelial cells and LDL oxidation seems to be mediated by Fe (Jeney et al., 2002; Nagy et al., 2010).

a(CHEBI:"oxidised LDL") positiveCorrelation a(CHEBI:heme) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Cerebral Hemorrhage
Text Location
Review

a(CHEBI:heme) positiveCorrelation a(CHEBI:"oxidised LDL") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Cerebral Hemorrhage
Text Location
Review

Evidence 6d0dfb19b0
JSON

mROS scavenger (Mito-TEMPO) and NADPH oxidases inhibitors (apocynin and DPI) block TNF production induced by heme.

a(CHEBI:TEMPO) decreases p(HGNC:TNF) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

a(CHEBI:apocynin) decreases p(HGNC:TNF) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

a(CHEBI:dibenziodolium) decreases p(HGNC:TNF) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

Evidence 042edb978f
JSON

mROS scavenger (Mito-TEMPO) and NADPH oxidases inhibitors (apocynin and DPI) block heme-induced necroptosis.

a(CHEBI:TEMPO) decreases bp(GO:"necroptotic process") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

a(CHEBI:apocynin) decreases bp(GO:"necroptotic process") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

a(CHEBI:dibenziodolium) decreases bp(GO:"necroptotic process") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

Evidence 71beb31d85
JSON

Heme injection in mice leads to vascular permeability, leukocyte migration from the intravascular environment to tissues and increase of acute-phase proteins (Lyoumi et al., 1999; Wagener et al., 2001b), hallmarks of acute inflammation.

a(CHEBI:heme) positiveCorrelation bp(GO:"regulation of vascular permeability") View Subject | View Object

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

a(CHEBI:heme) positiveCorrelation bp(GO:"leukocyte migration involved in inflammatory response") View Subject | View Object

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

bp(GO:"leukocyte migration involved in inflammatory response") positiveCorrelation a(CHEBI:heme) View Subject | View Object

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Annotations
Cell Ontology (CL)
erythrocyte
Text Location
Review

bp(GO:"regulation of vascular permeability") positiveCorrelation a(CHEBI:heme) View Subject | View Object

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

Evidence 81fefd8986
JSON

Heme activates endothelial cells inducing the expression of the adhesion molecules ICAM-1 (intercellular adhesion molecule 1), VCAM-1 (vascular cell adhesion molecule 1), E-selectin, Pselectin, and von Willebrand factor (VWF; Wagener et al., 1997; Belcher et al., 2014) and causes neutrophil migration (GraçaSouza et al., 2002; Porto et al., 2007).

a(CHEBI:heme) increases p(MGI:Icam1) View Subject | View Object

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

a(CHEBI:heme) increases p(MGI:Vcam1) View Subject | View Object

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

a(CHEBI:heme) increases bp(GO:"endothelial cell activation") View Subject | View Object

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

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

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

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

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

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

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

a(CHEBI:heme) increases bp(GO:"neutrophil migration") View Subject | View Object

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

Evidence 8e32f2a860
JSON

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).

deg(a(CHEBI:heme)) positiveCorrelation p(HGNC:HMOX1) View Subject | View Object

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

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p(HGNC:HMOX1) positiveCorrelation deg(a(CHEBI:heme)) View Subject | View Object

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Review

Evidence 42cf7c55fb
JSON

Heme amplifies cytokines induced by cell surface receptors (TLR2, TLR4, TLR5), endosome receptors (TLR3, TLR9), and cytosolic receptors (NOD1 and NOD2).

a(CHEBI:heme) increases a(MESH:Cytokines) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

a(CHEBI:heme) increases p(HGNC:TLR4) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

a(CHEBI:heme) increases p(HGNC:TLR2) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

a(CHEBI:heme) increases p(HGNC:TLR5) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

a(CHEBI:heme) increases p(HGNC:TLR9) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

a(CHEBI:heme) increases p(HGNC:NOD1) View Subject | View Object

Appears in Networks:
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Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

a(CHEBI:heme) increases p(HGNC:NOD2) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

Evidence c8297bb808
JSON

During intravascular hemolysis the serum proteins responsible for removing heme get saturated and heme can exert its inflammatory effects.

a(CHEBI:heme) increases path(MESH:Inflammation) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

Evidence 511a096672
JSON

The consequences of heme toxicity can be appreciated in hemolytic diseases such as β-thalassemia, sickle-cell disease (SCD), ischemia-reperfusion (IR), and malaria (Katori et al., 2002; Pamplona et al., 2007;Vinchi et al., 2013).

a(CHEBI:heme) positiveCorrelation path(MESH:"beta-Thalassemia") View Subject | View Object

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a(CHEBI:heme) positiveCorrelation path(MESH:"Anemia, Sickle Cell") View Subject | View Object

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Review

a(CHEBI:heme) positiveCorrelation path(MESH:"Reperfusion Injury") View Subject | View Object

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Text Location
Review

a(CHEBI:heme) positiveCorrelation path(MESH:Malaria) View Subject | View Object

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Text Location
Review

path(MESH:"Anemia, Sickle Cell") positiveCorrelation a(CHEBI:heme) View Subject | View Object

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Text Location
Review

path(MESH:"Reperfusion Injury") positiveCorrelation a(CHEBI:heme) View Subject | View Object

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Text Location
Review

path(MESH:"beta-Thalassemia") positiveCorrelation a(CHEBI:heme) View Subject | View Object

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Text Location
Review

path(MESH:Malaria) positiveCorrelation a(CHEBI:heme) View Subject | View Object

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Text Location
Review

Evidence eb22825170
JSON

. Heme can destabilize biological membranes increasing its permeability and the chance of lysis (Schmitt et al., 1993), as it happens with erythrocytes (Chiu and Lubin, 1989).

a(CHEBI:heme) increases bp(GO:"positive regulation of membrane permeability") View Subject | View Object

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Cell Ontology (CL)
erythrocyte
Text Location
Review

Evidence cd926ecce7
JSON

Alternatively, heme induced formation of radical species relies on the conversion of low-reactive organic hydroperoxides (ROOH) into highly reactive alkoxyl (RO•) and peroxyl (ROO•) radicals (Tappel, 1953, 1955; Van der Zee et al., 1996).

a(CHEBI:heme) increases rxn(reactants(a(CHEBI:hydroperoxide)), products(a(CHEBI:hydroperoxyl), a(MESH:"alkoxyl radical"))) View Subject | View Object

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

Evidence edd7a64175
JSON

In endothelial cells, heme induces TLR4-dependent degranulation of Weibel–Palade bodies and P-selectins and VWF release.

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

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

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

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

Evidence 839b9742e2
JSON

A seminal study demonstrated that the ability of heme to activate neutrophils depend on protein kinase C (PKC) activation and ROS generation, inducing the expression of adhesion molecules and modifying actin cytoskeleton dynamics, necessary features for neutrophils migration (Graça-Souza et al., 2002).

a(CHEBI:heme) increases bp(GO:"neutrophil migration") View Subject | View Object

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

a(MESH:"Protein Kinase C") increases bp(GO:"neutrophil migration") View Subject | View Object

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

a(MESH:"Reactive Oxygen Species") increases bp(GO:"neutrophil migration") View Subject | View Object

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

Evidence 1d1bedb6ec
JSON

Heme-induced neutrophils activation leads to extracellular traps (NETs) release through a mechanism dependent on ROS generation (Chen et al., 2014).

a(MESH:"Extracellular Traps") positiveCorrelation bp(GO:"neutrophil activation") View Subject | View Object

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

a(CHEBI:heme) increases bp(GO:"neutrophil activation") View Subject | View Object

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

bp(GO:"neutrophil activation") positiveCorrelation a(MESH:"Extracellular Traps") View Subject | View Object

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

Evidence e3cc49aef0
JSON

In this context, heme inhibits neutrophils apoptosis, increasing their longevity, and possibly enhancing harmful stimuli from these cells (Arruda et al., 2004, 2006).

a(CHEBI:heme) decreases bp(GO:"neutrophil apoptotic process") View Subject | View Object

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

Evidence 794ab79dee
JSON

. Heme activates macrophages inducing the production of TNF, KC (Figueiredo et al., 2007), IL-1β (unpublished), and LTB4 (Monteiro et al., 2011).

a(CHEBI:heme) increases p(HGNC:IL1B) View Subject | View Object

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Cell Ontology (CL)
erythrocyte
Text Location
Review

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

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Cell Ontology (CL)
erythrocyte
Text Location
Review

a(CHEBI:heme) increases a(CHEBI:"leukotriene B4") View Subject | View Object

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Cell Ontology (CL)
erythrocyte
Text Location
Review

Evidence cab881ef54
JSON

On the other hand, TNF secretion induced by heme is essential for the activation of the programed necrotic cell death pathway, which is denominated necroptosis (Fortes et al., 2012).

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

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Cell Ontology (CL)
erythrocyte
Text Location
Review

p(HGNC:TNF) increases bp(GO:"necroptotic process") View Subject | View Object

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Cell Ontology (CL)
erythrocyte
Text Location
Review

Evidence 2ec6832e25
JSON

Moreover, heme amplifies MyD88- (TNF and IL-6) and TRIF-dependent (IP-10) cytokines.

a(CHEBI:heme) increases p(HGNC:IL6) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

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

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

a(CHEBI:heme) increases p(HGNC:CXCL10) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

Evidence 71a3ce3866
JSON

Highly purified heme free of endotoxin contamination was used, as well as polymyxin B, anti-TLR4/MD2, and lipid A antagonist, all of which inhibited the effects of LPS but did not interfere with the induction of TNF by heme.

a(CHEBI:heme) increases p(RGD:Tnf) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

Evidence e0abab0ce9
JSON

The TLR4 activates two distinct pathways: MyD88 and TRIF. In macrophages, heme induces a biased MyD88 activation and the secretion of the pro-inflammatory cytokines TNF and KC.

a(CHEBI:heme) increases p(HGNC:TLR4) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

p(HGNC:TLR4) increases p(HGNC:MYD88) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

p(HGNC:TLR4) increases p(HGNC:TICAM1) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

Evidence 325827d071
JSON

Moreover, human embryonic kidney (HEK) cells transfected with human TLR4 secretes IL-8 upon stimulation with heme (Piazza et al., 2011).

a(CHEBI:heme) increases p(HGNC:TLR4) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

p(HGNC:TLR4) increases p(HGNC:MYD88) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

p(HGNC:MYD88) increases act(p(HGNC:NFKB1)) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

p(HGNC:NFKB1) increases p(HGNC:CXCL8) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

Evidence cafbc832fe
JSON

In fact, TLR4 is involved in intracerebral hemorrhage (ICH) induced by heme (Lin et al., 2012).

a(CHEBI:heme) increases p(HGNC:TLR4) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Cerebral Hemorrhage
Text Location
Review

Evidence 27aa6e93af
JSON

Moreover, HO-1 has a protective effect during heme-induced necroptosis.

a(CHEBI:heme) increases bp(GO:"necroptotic process") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

p(HGNC:HMOX1) decreases bp(GO:"necroptotic process") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

Evidence 77a82ec4e4
JSON

Therefore, it is clear that heme triggers ROS-induced sensitization of macrophages to TNFR-mediated cell death through RIP1 and RIP3 activation to promote necroptosis (Figure 2).

a(CHEBI:heme) increases bp(GO:"necroptotic process") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

Evidence bb07b03d17
JSON

Heme induces Syk phosphorylation in macrophages.

a(CHEBI:heme) increases p(HGNC:SYK, pmod(Ph)) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

Evidence 713921ad7c
JSON

Moreover, heme induces apoptosis in human brain vascular endothelial cells (HBVEC) by STAT3 (signal transducer and activator of transcription 3)-dependent activation of matrix metallopeptidase 3 (MMP3; Liu et al., 2013).

a(CHEBI:heme) increases bp(MESH:Apoptosis) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Cerebral Hemorrhage
Text Location
Review

Evidence aa6c77f118
JSON

These radicals may initiate further lipid peroxidation forming alkyl radicals that in the presence of O2 form more peroxyl radicals leading to a facile propagation of free radical reactions.

a(CHEBI:hydroperoxyl) increases bp(MESH:"Lipid Peroxidation") View Subject | View Object

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

a(MESH:"alkoxyl radical") increases bp(MESH:"Lipid Peroxidation") View Subject | View Object

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

Evidence 6741361833
JSON

. In the presence of reactive oxygen species (ROS), Hb is oxidized to methemoglobin (MetHb; Balla et al., 1993), characterized by the change in the oxidative state of the Fe present in the heme molecule from ferrous (Fe+2) to ferric (Fe+3).

a(MESH:"Reactive Oxygen Species") positiveCorrelation rxn(reactants(p(HGNC:HBB)), products(a(CHEBI:methemoglobin))) View Subject | View Object

Appears in Networks:
Annotations
Text Location
Review

rxn(reactants(p(HGNC:HBB)), products(a(CHEBI:methemoglobin))) positiveCorrelation a(MESH:"Reactive Oxygen Species") View Subject | View Object

Appears in Networks:
Annotations
Text Location
Review

Evidence a6509d38a2
JSON

Although neutrophils have important functions controlling infection, these cells can promote vascular and tissue injury by generating ROS, secreting proteases, and releasing extracellular chromatin (NETs; reviewed in Mócsai, 2013).

a(MESH:"Reactive Oxygen Species") positiveCorrelation a(MESH:Neutrophils) View Subject | View Object

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

a(MESH:Neutrophils) decreases path(MESH:Infection) View Subject | View Object

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

a(MESH:Neutrophils) positiveCorrelation a(MESH:"Reactive Oxygen Species") View Subject | View Object

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

Evidence adf4df1ed4
JSON

However, ROS is necessary to induce TNF secretion and MAPK activation.

a(MESH:"Reactive Oxygen Species") increases p(HGNC:TNF) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

a(MESH:"Reactive Oxygen Species") increases complex(p(HGNC:MAPK1), p(HGNC:MAPK14), p(HGNC:MAPK8)) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

Evidence 0edc9041ae
JSON

Because of its large molecular size, this complex is maintained in the intravascular space, preventing the association of otherwise free Hb with nitric oxide (NO; Reiter et al., 2002) and inhibiting the release of free heme (Melamed-Frank et al., 2001).

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

Appears in Networks:
Annotations
Text Location
Review

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

Appears in Networks:
Annotations
Text Location
Review

Evidence ff7477a312
JSON

Stimulation of astrocytes with heme, as a model of hemorrhagic injury, causes cell death with characteristics of programed necrosis including the loss of plasma membrane integrity, reversion by necrostatin-1, a selective inhibitor of RIP1, and by antioxidants (Laird et al., 2008).

a(MESH:"necrostatin-1") decreases p(HGNC:RIPK1) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

Evidence 7e1308411c
JSON

Hemoglobin is used as a nutrient by Plasmodium, the protozoan parasite that causes malaria, during its replication stage inside erythrocytes in the course of the infection in mammals (Francis et al., 1997).

a(MESH:Plasmodium) positiveCorrelation path(MESH:Malaria) View Subject | View Object

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

path(MESH:Malaria) positiveCorrelation a(MESH:Plasmodium) View Subject | View Object

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

Evidence 9d997d347e
JSON

Similarly to heme, ferrylHb activates endothelial cells through NFκB activation (Silva et al., 2009).

a(MESH:ferrylhemoglobin) increases bp(GO:"endothelial cell activation") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Cerebral Hemorrhage
Text Location
Review

Evidence 2363dd2ca3
JSON

Moreover, ferrylHb is unable to induce cytokine secretion by endothelial cells (Silva et al., 2009), another difference to heme which induces IL-8 production (Natarajan et al., 2007).

a(MESH:ferrylhemoglobin) causesNoChange a(MESH:Cytokines) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Cerebral Hemorrhage
Text Location
Review

a(MESH:ferrylhemoglobin) increases p(HGNC:CXCL8) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Cerebral Hemorrhage
Text Location
Review

Evidence 7e9d9e5b3d
JSON

Like MetHb, ferrylHb is unstable and releases free heme to further increase oxLDL formation (Potor et al., 2013).

a(MESH:ferrylhemoglobin) increases a(CHEBI:heme) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Cerebral Hemorrhage
Text Location
Review

Evidence a739dbe4b7
JSON

Similarly to heme, Hz also induces the production of several inflammatory mediators by macrophages such as cytokines and chemokines, and induces leukocytes migration (reviewed by Olivier et al., 2014).

a(MESH:hemozoin) increases a(MESH:Chemokines) View Subject | View Object

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

a(MESH:hemozoin) increases bp(GO:"leukocyte migration") View Subject | View Object

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

a(MESH:hemozoin) increases a(MESH:Cytokines) View Subject | View Object

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

Evidence bed13a28eb
JSON

Atypical hemolytic uremic syndrome (aHUS) is characterized by an over activation of the complement alternative pathway (CAP) due to genetic and acquired abnormalities (Noris and Remuzzi, 2009).

bp(GO:"complement activation, alternative pathway") positiveCorrelation path(MESH:"Atypical Hemolytic Uremic Syndrome") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Cerebral Hemorrhage
Text Location
Review

path(MESH:"Atypical Hemolytic Uremic Syndrome") positiveCorrelation bp(GO:"complement activation, alternative pathway") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Cerebral Hemorrhage
Text Location
Review

Evidence 8406bd752d
JSON

Once inside the cells, heme is catabolized by HO enzymes, generating equimolar amounts of biliverdin, carbon monoxide (CO), and Fe (Tenhunen et al., 1968).

bp(GO:"heme catabolic process") positiveCorrelation p(HGNC:HMOX1) View Subject | View Object

Appears in Networks:
Annotations
Text Location
Review

bp(GO:"heme catabolic process") increases a(MESH:Biliverdine) View Subject | View Object

Appears in Networks:
Annotations
Text Location
Review

bp(GO:"heme catabolic process") increases a(CHEBI:"carbon monoxide") View Subject | View Object

Appears in Networks:
Annotations
Text Location
Review

bp(GO:"heme catabolic process") increases a(CHEBI:"iron(2+)") View Subject | View Object

Appears in Networks:
Annotations
Text Location
Review

p(HGNC:HMOX1) positiveCorrelation bp(GO:"heme catabolic process") View Subject | View Object

Appears in Networks:
Annotations
Text Location
Review

Evidence 1e0df1d9e3
JSON

LXR-β protects against lipid overload by activating a lipid exportation program regulated by proteins such as LXR-α and ATP binding cassette transporter A1 (ABCA1), preventing foam cells formation.

bp(GO:"lipid homeostasis") positiveCorrelation p(HGNC:NR1H2) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Cerebral Hemorrhage
Text Location
Review

p(HGNC:NR1H2) positiveCorrelation bp(GO:"lipid homeostasis") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Cerebral Hemorrhage
Text Location
Review

Evidence a15354fafe
JSON

Hemolysis increases the concentration of Hb which, under oxidative stress, releases free heme.

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

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

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

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

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

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

Evidence 5d2ad9e63c
JSON

In vivo, injection of heme and LPS induces a significant increase in the concentrations of TNF and IL-6 when compared to the challenge with LPS alone (Fernandez et al., 2010).

complex(a(CHEBI:heme), a(MESH:Lipopolysaccharides)) increases p(HGNC:TNF) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Cerebral Hemorrhage
Text Location
Review

complex(a(CHEBI:heme), a(MESH:Lipopolysaccharides)) increases p(HGNC:IL6) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Cerebral Hemorrhage
Text Location
Review

Evidence 50dc1b63c3
JSON

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.

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

Appears in Networks:
Annotations
Text Location
Review

p(HGNC:LRP1) increases bp(GO:"heme catabolic process") View Subject | View Object

Appears in Networks:
Annotations
Text Location
Review

Evidence c0996ece7c
JSON

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).

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

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

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

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

Evidence f7c8c219c6
JSON

TLR4 activation leads to MAPKs and NFκB activation, which are necessary to TNF secretion.

p(HGNC:TLR4) increases complex(p(HGNC:MAPK1), p(HGNC:MAPK14), p(HGNC:MAPK8)) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

p(HGNC:TLR4) increases p(HGNC:NFKB1) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

complex(p(HGNC:MAPK1), p(HGNC:MAPK14), p(HGNC:MAPK8)) increases p(HGNC:TNF) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

p(HGNC:NFKB1) increases p(HGNC:TNF) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

Evidence d6a9e8a0db
JSON

In fact, Tlr4-/- or anti-TLR4 treatment suppresses heme-induced neuroinflammation, edema, and neurologic deficit.

p(HGNC:TLR4) positiveCorrelation path(MESH:"Neurogenic Inflammation") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Cerebral Hemorrhage
Text Location
Review

p(HGNC:TLR4) positiveCorrelation path(MESH:"Brain Edema") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Cerebral Hemorrhage
Text Location
Review

path(MESH:"Brain Edema") positiveCorrelation p(HGNC:TLR4) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Cerebral Hemorrhage
Text Location
Review

path(MESH:"Neurogenic Inflammation") positiveCorrelation p(HGNC:TLR4) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Cerebral Hemorrhage
Text Location
Review

Evidence b0c62e824e
JSON

Indeed, TLRs and NLRP3 have been associated with atherosclerosis development.

p(HGNC:TLR4) increases path(MESH:Atherosclerosis) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Cerebral Hemorrhage
Text Location
Review

p(HGNC:NLRP3) increases path(MESH:Atherosclerosis) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Cerebral Hemorrhage
Text Location
Review

p(HGNC:TLR6) increases path(MESH:Atherosclerosis) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Cerebral Hemorrhage
Text Location
Review

Evidence b028f5e382
JSON

After hemolysis, sustained interaction between Hb and ROS can lead to ferrylhemoglobin (ferrylHb) formation, which is characterized by an increase in the Fe oxidative state to Fe+4 (Harel and Kanner, 1988; Patel et al., 1996).

complex(a(MESH:"Reactive Oxygen Species"), p(HGNC:HBB)) increases a(MESH:ferrylhemoglobin) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Cerebral Hemorrhage
Text Location
Review

Evidence a02c41a7ae
JSON

Hb synergizes with LPS enhancing the production of pro-inflammatory cytokines by macrophages (Yang et al., 2002).

complex(a(MESH:Lipopolysaccharides), p(HGNC:HBB)) increases a(MESH:Cytokines) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Cerebral Hemorrhage
Text Location
Review

Evidence 55072721ac
JSON

WhileMAPK8 increases ROS generation, TNF induces RIP1–RIP3 necrosome which triggers necroptosis.

p(HGNC:RIPK3) increases bp(GO:"necroptotic process") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

p(HGNC:TNF) increases act(p(HGNC:RIPK1)) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

p(HGNC:MAPK8) increases a(MESH:"Reactive Oxygen Species") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

p(HGNC:TNF) increases act(p(HGNC:RIPK3)) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

p(HGNC:RIPK1) increases bp(GO:"necroptotic process") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

Evidence 532a56f2e2
JSON

Cells deficient on FtH are more susceptible to oxidative damage, while increased amounts of FtH protects cells from death induced by challenges such as Fe, tumor necrosis factor (TNF), heme, heme plus TNF, or oxidized low-density lipoprotein (LDL; Juckett et al., 1995; Pham et al., 2004; Gozzelino et al., 2012).

p(HGNC:FTH1) decreases bp(MESH:"Oxidative Stress") View Subject | View Object

Appears in Networks:
Annotations
Text Location
Review

p(HGNC:FTH1) decreases p(HGNC:TNF) View Subject | View Object

Appears in Networks:
Annotations
Text Location
Review

p(HGNC:FTH1) decreases a(CHEBI:"iron(2+)") View Subject | View Object

Appears in Networks:
Annotations
Text Location
Review

p(HGNC:FTH1) decreases a(CHEBI:heme) View Subject | View Object

Appears in Networks:
Annotations
Text Location
Review

p(HGNC:FTH1) decreases a(CHEBI:"oxidised LDL") View Subject | View Object

Appears in Networks:
Annotations
Text Location
Review

Evidence 8e95e5f192
JSON

Importantly, increased expression of FtH also protects different cell types from the cytotoxic effects of heme, TNF or heme and TNF (Balla et al., 1992; Berberat et al., 2003; Cozzi et al., 2003; Gozzelino et al., 2012).

p(HGNC:FTH1) decreases path(HM:"Heme cytotoxicity") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Cerebral Hemorrhage
Text Location
Review

Evidence dbe9854215
JSON

The antioxidant property of FtH blocks TNF-induced JNK activation, reducing cell death (Pham et al., 2004; Kamata et al., 2005; Gozzelino et al., 2012).

p(HGNC:FTH1) decreases p(HGNC:MAPK8) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Cerebral Hemorrhage
Text Location
Review

Evidence dc50f5637d
JSON

Interestingly, a 6-year-old patient with HO-1 deficiency experienced a severe atherosclerotic pathology (Yachie et al., 1999).

p(HGNC:HMOX1) decreases path(MESH:Atherosclerosis) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Cerebral Hemorrhage
Text Location
Review

Evidence 890137ee47
JSON

During the resolution phase of inflammation HO-1 expression in leukocytes reduces adhesion molecules expression and leukocytes migration, thus contributing to wound healing (Wagener et al., 2003a).

p(HGNC:HMOX1) decreases a(MESH:"Cell Adhesion Molecules") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

p(HGNC:HMOX1) decreases bp(GO:"leukocyte migration") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

p(HGNC:HMOX1) increases bp(MESH:"Wound Healing") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

Evidence 7c11771873
JSON

Moreover, IL-1β and TNF modifies the hypothalamus threshold of the body temperature causing fever.

p(HGNC:IL1B) positiveCorrelation path(MESH:Fever) View Subject | View Object

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

p(HGNC:TNF) positiveCorrelation path(MESH:Fever) View Subject | View Object

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

path(MESH:Fever) positiveCorrelation p(HGNC:TNF) View Subject | View Object

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

path(MESH:Fever) positiveCorrelation p(HGNC:IL1B) View Subject | View Object

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

Evidence 95ecd1a4ee
JSON

Although KC and IL-1β functions were not investigated during heme-induced inflammatory effects, TNF and LTB4 were described as essential inflammatory mediators during inflammatory events induced by heme.

p(HGNC:IL1B) increases path(MESH:Inflammation) View Subject | View Object

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

p(HGNC:TNF) increases path(MESH:Inflammation) View Subject | View Object

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

Evidence a817c40ae5
JSON

The MyD88-dependent pathway leads to the activation of mitogen-activated protein kinases (MAPKs) and NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) transcription factors inducing the expression of inflammatory cytokines such as TNF, IL-6, IL-1β, and KC (Takeuchi and Akira, 2010)

act(p(HGNC:IRF3)) increases p(HGNC:IFNA1) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

act(p(HGNC:IRF3)) increases p(HGNC:NFKB1) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

p(HGNC:TICAM1) increases act(p(HGNC:IRF3)) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

Evidence cf750bb70c
JSON

. Interestingly, NLRP3 knockdown and mROS inhibitors reduce brain edema and improve neurological functions (Ma et al., 2014).

p(HGNC:NLRP3) positiveCorrelation path(MESH:"Brain Edema") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Cerebral Hemorrhage
Text Location
Review

path(MESH:"Brain Edema") positiveCorrelation p(HGNC:NLRP3) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Cerebral Hemorrhage
Text Location
Review

Evidence fac6eaa740
JSON

The VWF is prothrombotic and can increase the adhesion of erythrocytes to the endothelium.

p(HGNC:VWF) positiveCorrelation path(MESH:Thrombosis) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

path(MESH:Thrombosis) positiveCorrelation p(HGNC:VWF) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

Evidence 55500014f3
JSON

Mice lacking HO-1 (Hmox1−/−) are highly susceptible to pathologic conditions associated with increased serum heme concentration.

p(MGI:Hmox1) decreases a(CHEBI:heme) View Subject | View Object

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

Evidence df6bc0c14d
JSON

For instance, Hmox−/− mice develops acute renal failure and marked mortality when submitted to rhabdomyolysis, a pathological condition that increases serum myoglobin which can be oxidized and release heme (Nath et al., 2000).

p(MGI:Hmox1) negativeCorrelation path(MESH:"Acute Kidney Injury") View Subject | View Object

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

p(MGI:Mb) positiveCorrelation path(MESH:Rhabdomyolysis) View Subject | View Object

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

path(MESH:"Acute Kidney Injury") negativeCorrelation p(MGI:Hmox1) View Subject | View Object

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

path(MESH:Rhabdomyolysis) positiveCorrelation p(MGI:Mb) View Subject | View Object

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

Evidence 8a130e6db7
JSON

Furthermore, Hmox1−/− mice are susceptible to liver IR which is characterized by tissue damage in sites that are reperfused after ischemia injury and hemolysis (Devey et al., 2009).

p(MGI:Hmox1) negativeCorrelation path(MESH:"Insulin Resistance") View Subject | View Object

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

path(MESH:"Insulin Resistance") negativeCorrelation p(MGI:Hmox1) View Subject | View Object

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

Evidence c2a9696c59
JSON

Depending on the extension of the vaso-occlusion, some tissues may experience hypoxia and damage.

path(HM:"vaso-occlusive crisis") positiveCorrelation path(MESH:Hypoxia) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

path(MESH:Hypoxia) positiveCorrelation path(HM:"vaso-occlusive crisis") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

Evidence 83bf50cd4e
JSON

Vaso-occlusion of the lung microvasculature may result in the development of the ACS through the infarction of the lung parenchyma.

path(HM:"vaso-occlusive crisis") positiveCorrelation path(MESH:"Acute Chest Syndrome") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

path(MESH:"Acute Chest Syndrome") positiveCorrelation path(HM:"vaso-occlusive crisis") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

Evidence a7d79d8bf4
JSON

SCD and β-thalassemia are genetic diseases associated to erythrocytes that are prone to lysis due to defective Hb production (Heinle and Read, 1948; Pauling et al., 1949; Ingram, 1957; discussed later).

path(MESH:"Anemia, Sickle Cell") positiveCorrelation path(MESH:Hemolysis) View Subject | View Object

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

path(MESH:"beta-Thalassemia") positiveCorrelation path(MESH:Hemolysis) View Subject | View Object

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

path(MESH:Hemolysis) positiveCorrelation path(MESH:"Anemia, Sickle Cell") View Subject | View Object

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

path(MESH:Hemolysis) positiveCorrelation path(MESH:"beta-Thalassemia") View Subject | View Object

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

Evidence 8ba8d986de
JSON

Hemolysis can happen due to ischemia/reperfusion, SCD or β-thalassemia.

path(MESH:Hemolysis) positiveCorrelation path(MESH:Thalassemia) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

path(MESH:"Anemia, Sickle Cell") positiveCorrelation path(MESH:Hemolysis) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

path(MESH:Hemolysis) positiveCorrelation path(MESH:"Anemia, Sickle Cell") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

path(MESH:Hemolysis) positiveCorrelation path(MESH:Ischemia) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

path(MESH:Ischemia) positiveCorrelation path(MESH:Hemolysis) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

path(MESH:Thalassemia) positiveCorrelation path(MESH:Hemolysis) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

About

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.