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a(CHEBI:"nitric oxide")

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Entity

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

Appears in Networks 8

Nicotinic acetylcholine receptor signalling: roles in Alzheimer's disease and amyloid neuroprotection. v1.0.0

Tau Modifications v1.9.5

Tau Modifications Sections of NESTOR

Inflammasome activation and innate immunity in Alzheimer’s disease v1.0.2

Activation and regulation of the inflammasomes v1.0.0

Inflammasome Involvement in Alzheimer’s Disease v1.0.0

Nuclear Factor Kappa-light-chain-enhancer of Activated B Cells (NF-κB) - a Friend, a Foe, or a Bystander - in the Neurodegenerative Cascade and Pathogenesis of Alzheimer's Disease v1.0.0

Phytochemicals as inhibitors of NF-κB for treatment of Alzheimer’s disease v1.0.0

Heme Curation v0.0.1-dev

Mechanistic knowledge surrounding heme

In-Edges 47

act(p(HGNC:NOS1)) increases a(CHEBI:"nitric oxide") View Subject | View Object

Nicotine also activates ERK in non-neuronal cells such as pancreatic acinar cells (Chowdhury et al., 2007) and vascular smooth muscle cells (Kanda and Watanabe, 2007), although it is not known in those cases which nAChR subtypes are involved. In the cortex and hippocampus of mice, nicotine’s inhibition of MAPK (shown by RNAi reduction of alpha7 expression to be alpha7-dependent) prevents activation of nuclear factor- kappaB and c-Myc, also thereby reducing the activity of inducible nitric-oxide synthetase and NO production and decreasing Abeta production (Liu et al., 2007). PubMed:19293145

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Annotations
Cell Ontology (CL)
pancreatic acinar cell
Cell Ontology (CL)
vascular associated smooth muscle cell

a(HBP:"8-nitro-cGMP") positiveCorrelation a(CHEBI:"nitric oxide") View Subject | View Object

Tau contains cysteine residues in the microtubule binding region following alternative splicing of exon 10, and formation of intermolecular cysteine disulfide bonds accelerates tau aggregation. 8-Nitro-cGMP (novel second messenger of NO) exposure induced S-guanylation of tau both in vitro and in tau-overexpressed HEK293T cells. S-guanylated tau inhibited heparin-induced tau aggregation (thioflavin T). S-guanylated tau could not form tau granules and fibrils (AFM) inhibited at the step of tau oligomer formation. In P301L tau-expressing Neuro2A cells, 8-nitro-cGMP reduced the amount of sarcosyl-insoluble tau. NO-linked chemical modification on cysteine residues of tau could block tau aggregation PubMed:27601475

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act(p(ECCODE:"1.14.13.39")) directlyIncreases a(CHEBI:"nitric oxide") View Subject | View Object

Tau contains cysteine residues in the microtubule binding region following alternative splicing of exon 10, and formation of intermolecular cysteine disulfide bonds accelerates tau aggregation. 8-Nitro-cGMP (novel second messenger of NO) exposure induced S-guanylation of tau both in vitro and in tau-overexpressed HEK293T cells. S-guanylated tau inhibited heparin-induced tau aggregation (thioflavin T). S-guanylated tau could not form tau granules and fibrils (AFM) inhibited at the step of tau oligomer formation. In P301L tau-expressing Neuro2A cells, 8-nitro-cGMP reduced the amount of sarcosyl-insoluble tau. NO-linked chemical modification on cysteine residues of tau could block tau aggregation PubMed:27601475

Appears in Networks:

p(HGNC:APP, frag("672_713")) increases a(CHEBI:"nitric oxide") View Subject | View Object

We found that NO production and tau acetylation at Lys280 occurred in the brain tissue in mice and in cultured mouse cortical neurons in response to exposure to amyloid-β1-42 (Aβ1-42), a peptide that is also implicated in AD. An increased abundance of NO facilitated the S-nitrosylation (SNO) of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). S-nitrosylated GAPDH (GAPDH-SNO) promoted the acetylation and activation of the acetyltransferase p300 and facilitated the nitrosylation and inactivation of the deacetylase sirtuin 1 (SIRT1). The abundance of GAPDH-SNO was increased in postmortem brain samples from AD patients. Preventing the increase in GAPDH-SNO abundance in both cultured neurons and mice, either by overexpression of the nitrosylation mutant of GAPDH (GAPDH C150S) or by treatment with the GAPDH nitrosylation inhibitor CGP3466B (also known as omigapil), abrogated Aβ1-42-induced tau acetylation, memory impairment, and locomotor dysfunction in mice, suggesting that this drug might be repurposed to treat patients with AD. PubMed:29559585

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a(CHEBI:"amyloid-beta") increases a(CHEBI:"nitric oxide") View Subject | View Object

NLRP3 inflammasome formation and subsequent activation of caspase-1 cleavage capacity was instrumental for Abeta-induced nitric oxide production and TNF-a release PubMed:28019679

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Annotations
Confidence
High
NeuroMMSigDB
Amyloidogenic subgraph
NeuroMMSigDB
Nitric oxide subgraph

complex(GO:"NLRP3 inflammasome complex") increases a(CHEBI:"nitric oxide") View Subject | View Object

NLRP3 inflammasome formation and subsequent activation of caspase-1 cleavage capacity was instrumental for Abeta-induced nitric oxide production and TNF-a release PubMed:28019679

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Annotations
Confidence
High
NeuroMMSigDB
Caspase subgraph
NeuroMMSigDB
Nitric oxide subgraph

act(p(HGNC:CASP1)) increases a(CHEBI:"nitric oxide") View Subject | View Object

NLRP3 inflammasome formation and subsequent activation of caspase-1 cleavage capacity was instrumental for Abeta-induced nitric oxide production and TNF-a release PubMed:28019679

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Annotations
Confidence
High
NeuroMMSigDB
Caspase subgraph
NeuroMMSigDB
Nitric oxide subgraph

act(p(HGNC:NOS2)) increases a(CHEBI:"nitric oxide") View Subject | View Object

In addition, T cell-derived IFNγ has been shown to downregulate the activity of NLRP3 via activation of inducible nitric oxide synthase (iNOS) in a mouse model of tuberculosis71; nitric oxide (NO) induces NLRP3 nitrosylation and thereby inhibits NLRP3 activity. PubMed:23702978

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Caspase subgraph
NeuroMMSigDB
Interferon signaling subgraph
NeuroMMSigDB
Nitric oxide subgraph

act(p(HGNC:NOS2)) increases a(CHEBI:"nitric oxide") View Subject | View Object

It is noteworthy that IL-1 beta and IL-18 can activate various cell types, par- ticularly astrocytes and microglia to induce additional cytokine release involving IL-1 beta , IL-6, and IL-18, and also nitric oxide (NO) synthase that can stimulate production of free radical NO, leading to the forma- tion of peroxynitrite that denatures DNA and impairs cellular energy pathways [48, 49]. PubMed:27314526

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Brain
MeSH
Cerebrospinal Fluid
MeSH
Serum
MeSH
Alzheimer Disease
NeuroMMSigDB
Interleukin signaling subgraph
NeuroMMSigDB
Nitric oxide subgraph

a(CHEBI:"1,8-cineole") decreases a(CHEBI:"nitric oxide") View Subject | View Object

The mitochondrial membrane potential, ROS and NO levels were down-regulated by 1,8-cineole in A 25-35-stimulated cells [250]. PubMed:29179999

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Annotations
MeSH
Alzheimer Disease

a(CHEBI:"alpha-tocopherol") decreases a(CHEBI:"nitric oxide") View Subject | View Object

Reduction of A expression and cytotoxic-ity stimulated by A in neuroblastoma cells and the inhibition of inflammatory cytokines, ROS and NO in microglial cells were detected upon treatment with -tocopherol [210]. PubMed:29179999

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Annotations
Cell Ontology (CL)
microglial cell

a(CHEBI:resveratrol) decreases a(CHEBI:"nitric oxide") View Subject | View Object

It also lowered the expression of NO and iNOS, and prostaglandin E2 (PGE2) and COX2 in A-activated glial cells. All these effects were attributableto their suppression of nuclear NF-B translocation [116]. PubMed:29179999

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a(PUBCHEM:102336202) decreases a(CHEBI:"nitric oxide") View Subject | View Object

Xanthoceraside decreased the expression of A 25-35/IFN--stimulated NO, IL-1,and TNF- in microglia, which implicated the down-regulation of the activities of MAPK and NF-B pathways [248] PubMed:29179999

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Annotations
Cell Ontology (CL)
microglial cell

a(PUBCHEM:14193399) decreases a(CHEBI:"nitric oxide") View Subject | View Object

Glaucocalyxin B, found in Rabdosia japonica, considerably atten-uated the expression of NO, TNF-, IL-1, COX-2 and iNOS in LPS-induced microglia cells [169–172]. Moreover, the activation of NF-B, p38 MAPK and ROS generation was interrupted by glauco- calyxin B in LPS-induced microglia cells [172]. PubMed:29179999

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Annotations
Cell Ontology (CL)
microglial cell

a(PUBCHEM:440312) decreases a(CHEBI:"nitric oxide") View Subject | View Object

LPS-activated expression of pro-inflammatory and neurotoxic factors like NO, TNF-, PGE2, NO synthase and COX2 production and LOX activity were inhibited by dihydroasparagusic acid in microglia cells [243]. PubMed:29179999

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Annotations
Cell Ontology (CL)
microglial cell

a(CHEBI:"iron(2+)") decreases a(CHEBI:"nitric oxide") View Subject | View Object

Extracellular hemoglobin and its degradation products, free heme and iron, are highly toxic due to oxidative stress induction and decrease in nitric oxide availability. PubMed:28088643

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

a(CHEBI:"iron(2+)") decreases a(CHEBI:"nitric oxide") View Subject | View Object

Hb and its degradation products – free heme and iron - perpetuate oxidative stress, and together with decreased NO availability promote many SCD complications. PubMed:28088643

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

a(CHEBI:"phosphatidyl-L-serine") decreases a(CHEBI:"nitric oxide") View Subject | View Object

In addition to cell-free Hb, membrane structural modification, externalization of phosphatidylserine,21 decreased cell membrane deformability,22,23 and increased endothelial adherence24 could alter vascular NO homeostasis. PubMed:27308950

Appears in Networks:
Annotations
MeSH
Endothelium, Vascular
Text Location
Introduction

a(CHEBI:heme) decreases a(CHEBI:"nitric oxide") View Subject | View Object

Free plasma haemoglobin and haem also scavenge NO and have multiple pro-inflammatory and pro-oxidant properties that mediate many of the adverse effects of haemolysis. PubMed:25307023

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Plasma
MeSH
Urine
Text Location
Review

a(CHEBI:heme) negativeCorrelation a(CHEBI:"nitric oxide") View Subject | View Object

The main mediator of these adverse effects is thought to be free haem via its effects on NO scavenging, pro-inflammatory cytokine responses, and reactive oxygen species (ROS) generation. PubMed:25307023

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Plasma
MeSH
Urine
MeSH
Anemia, Hemolytic, Autoimmune
Text Location
Review

a(CHEBI:heme) decreases a(CHEBI:"nitric oxide") View Subject | View Object

Extracellular hemoglobin and its degradation products, free heme and iron, are highly toxic due to oxidative stress induction and decrease in nitric oxide availability. PubMed:28088643

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

a(CHEBI:heme) decreases a(CHEBI:"nitric oxide") View Subject | View Object

Hb and its degradation products – free heme and iron - perpetuate oxidative stress, and together with decreased NO availability promote many SCD complications. PubMed:28088643

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

a(CHEBI:heme) decreases a(CHEBI:"nitric oxide") View Subject | View Object

Heme promotes endothelial dysfunction by inducing the expression of adhesion molecules and reducing nitric oxide (NO) availability, which causes vasoconstriction [9-14]. PubMed:28400318

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Annotations
Cell Ontology (CL)
endothelial cell
Text Location
Introduction

a(HM:"stored erythrocytes") decreases a(CHEBI:"nitric oxide") View Subject | View Object

In the current observational study in patients undergoing multilevel spinal fusion surgery, we tested the hypothesis that moderate doses of stored RBC transfusions increase intravascular cell-free Hb and decrease NO availability in surgical patients. PubMed:27308950

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Annotations
MeSH
Endothelium, Vascular
Text Location
Introduction

a(HM:"stored erythrocytes") decreases a(CHEBI:"nitric oxide") View Subject | View Object

Stored RBCs undergo a complex structural and metabolic impairment that includes leakage of hemoglobin from the cells and hemolysis, reduced energy and NO production, formation of toxic products, such as lysophospholipids and free iron, phosphatidylserine exposure and shedding MPs [59]. PubMed:28458720

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

bp(GO:"endothelial cell activation") decreases a(CHEBI:"nitric oxide") View Subject | View Object

In addition to cell-free Hb, membrane structural modification, externalization of phosphatidylserine,21 decreased cell membrane deformability,22,23 and increased endothelial adherence24 could alter vascular NO homeostasis. PubMed:27308950

Appears in Networks:
Annotations
MeSH
Endothelium, Vascular
Text Location
Introduction

bp(GO:vasoconstriction) negativeCorrelation a(CHEBI:"nitric oxide") View Subject | View Object

Heme promotes endothelial dysfunction by inducing the expression of adhesion molecules and reducing nitric oxide (NO) availability, which causes vasoconstriction [9-14]. PubMed:28400318

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Annotations
Cell Ontology (CL)
endothelial cell
Text Location
Introduction

bp(MESH:"Erythrocyte Aggregation") decreases a(CHEBI:"nitric oxide") View Subject | View Object

Another consequence of the axial RBC accumulation followed by reduction in local viscosity is a decrease of the wall shear stress causing a lesser local release of nitric oxide [15]. PubMed:28458720

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Text Location
Review

p(HGNC:HBB) decreases a(CHEBI:"nitric oxide") View Subject | View Object

Free plasma haemoglobin and haem also scavenge NO and have multiple pro-inflammatory and pro-oxidant properties that mediate many of the adverse effects of haemolysis. PubMed:25307023

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Plasma
MeSH
Urine
Text Location
Review

p(HGNC:HBB) decreases a(CHEBI:"nitric oxide") View Subject | View Object

In addition to cell-free Hb, membrane structural modification, externalization of phosphatidylserine,21 decreased cell membrane deformability,22,23 and increased endothelial adherence24 could alter vascular NO homeostasis. PubMed:27308950

Appears in Networks:
Annotations
MeSH
Endothelium, Vascular
Text Location
Introduction

p(HGNC:HBB) negativeCorrelation a(CHEBI:"nitric oxide") View Subject | View Object

Plasma hemoglobin scavenges nitric oxide and causes vasoconstriction, platelet aggregation and inflammation9,22–24. PubMed:27515135

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Annotations
Text Location
Introduction

p(HGNC:HBB) decreases a(CHEBI:"nitric oxide") View Subject | View Object

Extracellular hemoglobin and its degradation products, free heme and iron, are highly toxic due to oxidative stress induction and decrease in nitric oxide availability. PubMed:28088643

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

p(HGNC:HBB) decreases a(CHEBI:"nitric oxide") View Subject | View Object

Extracellular Hb exhibits a highly toxic nature by scavenging Nitric Oxide (NO) that reduces its bioavailability [1]. PubMed:28088643

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

p(HGNC:HBB) decreases a(CHEBI:"nitric oxide") View Subject | View Object

Some of the adverse effects caused by cell-free hemoglobin are a result of depletion of nitric oxide (NO), which may lead to vasoconstriction, inflammation, and platelet activation (10, 24). PubMed:28314763

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Text Location
Introduction

p(HGNC:HBB) decreases a(CHEBI:"nitric oxide") View Subject | View Object

Another mechanism for platelet activation by RBC lysate is extracellular hemoglobin, which enhances platelet activation by lowering NO bioavailability [ 29]. PubMed:28458720

Appears in Networks:
Annotations
MeSH
Veins
Text Location
Review

p(HGNC:HBB) decreases a(CHEBI:"nitric oxide") View Subject | View Object

Extracellular hemoglobin sequesters NO and thus promotes activation of endothelial cells and adhesion/aggregation of platelets [64]. PubMed:28458720

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

p(HGNC:HBB) decreases a(CHEBI:"nitric oxide") View Subject | View Object

The first process links the nitric oxide (NO) reactivity of oxyHb to a cascade of cell-free Hb extravasation, hemolysis-associated NO-depletion, and vasoconstriction.21–23 PubMed:29610666

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Annotations
Cell Ontology (CL)
macrophage
MeSH
Mitochondria
Text Location
Discussion

p(HGNC:HBB) decreases a(CHEBI:"nitric oxide") View Subject | View Object

One of the mechanisms by which cell-free hemoglobin exerts its detrimental effects is its ability to effectively scavenge nitric oxide (NO), which in turn leads to perfusion disorders and an increased arterial and pulmonary arterial pressure [39, 40]. PubMed:29956069

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Annotations
MeSH
Arteries
MeSH
Sepsis
Text Location
Review

complex(a(CHEBI:"nitric oxide"), p(HGNC:HBB)) hasComponent a(CHEBI:"nitric oxide") View Subject | View Object

Appears in Networks:

complex(a(CHEBI:heme), p(INTERPRO:"NEAT domain")) increases a(CHEBI:"nitric oxide") View Subject | View Object

This ability of NEAT can decrease the level of NO scavenging and oxidative stress in SCD. PubMed:28088643

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

p(HGNC:NOS3) increases a(CHEBI:"nitric oxide") View Subject | View Object

It is unlikely that loss of nitrite through surgically shed blood and hemodilution would produce a decrease of 50% from baseline because continuous synthesis of NO by eNOS should replenish the loss of nitrite. PubMed:27308950

Appears in Networks:
Annotations
MeSH
Plasma
Text Location
Discussion

path(MESH:Hemolysis) decreases a(CHEBI:"nitric oxide") View Subject | View Object

During intravascular haemolysis, NO availability is severely limited by its reaction with oxyhaemoglobin (i.e., NO scavenging) and by breakdown of the substrate for NO synthesis, L-arginine, by arginase released from RBCs (Schnog et al, 2004). PubMed:25307023

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Plasma
MeSH
Urine
MeSH
Anemia, Hemolytic, Autoimmune
Text Location
Review

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

Appears in Networks:

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

Appears in Networks:

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

Appears in Networks:

rxn(reactants(a(CHEBI:arginine)), products(a(CHEBI:ornithine))) decreases a(CHEBI:"nitric oxide") View Subject | View Object

Both processes decrease the availability of NO, which normally maintains smooth muscle cell relaxation, inhibits platelet activation and aggregation, and has anti-inflammatory effects on the endothelium. PubMed:29929138

Appears in Networks:
Annotations
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

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

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Out-Edges 27

a(CHEBI:"nitric oxide") increases p(MGI:Gapdh, pmod(NO)) View Subject | View Object

We found that NO production and tau acetylation at Lys280 occurred in the brain tissue in mice and in cultured mouse cortical neurons in response to exposure to amyloid-β1-42 (Aβ1-42), a peptide that is also implicated in AD. An increased abundance of NO facilitated the S-nitrosylation (SNO) of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). S-nitrosylated GAPDH (GAPDH-SNO) promoted the acetylation and activation of the acetyltransferase p300 and facilitated the nitrosylation and inactivation of the deacetylase sirtuin 1 (SIRT1). The abundance of GAPDH-SNO was increased in postmortem brain samples from AD patients. Preventing the increase in GAPDH-SNO abundance in both cultured neurons and mice, either by overexpression of the nitrosylation mutant of GAPDH (GAPDH C150S) or by treatment with the GAPDH nitrosylation inhibitor CGP3466B (also known as omigapil), abrogated Aβ1-42-induced tau acetylation, memory impairment, and locomotor dysfunction in mice, suggesting that this drug might be repurposed to treat patients with AD. PubMed:29559585

Appears in Networks:

a(CHEBI:"nitric oxide") positiveCorrelation a(HBP:"8-nitro-cGMP") View Subject | View Object

Tau contains cysteine residues in the microtubule binding region following alternative splicing of exon 10, and formation of intermolecular cysteine disulfide bonds accelerates tau aggregation. 8-Nitro-cGMP (novel second messenger of NO) exposure induced S-guanylation of tau both in vitro and in tau-overexpressed HEK293T cells. S-guanylated tau inhibited heparin-induced tau aggregation (thioflavin T). S-guanylated tau could not form tau granules and fibrils (AFM) inhibited at the step of tau oligomer formation. In P301L tau-expressing Neuro2A cells, 8-nitro-cGMP reduced the amount of sarcosyl-insoluble tau. NO-linked chemical modification on cysteine residues of tau could block tau aggregation PubMed:27601475

Appears in Networks:

a(CHEBI:"nitric oxide") increases p(HGNC:NLRP3, pmod(NO)) View Subject | View Object

In addition, T cell-derived IFNγ has been shown to downregulate the activity of NLRP3 via activation of inducible nitric oxide synthase (iNOS) in a mouse model of tuberculosis71; nitric oxide (NO) induces NLRP3 nitrosylation and thereby inhibits NLRP3 activity. PubMed:23702978

Appears in Networks:
Annotations
Confidence
High
NeuroMMSigDB
Caspase subgraph
NeuroMMSigDB
Interferon signaling subgraph
NeuroMMSigDB
Nitric oxide subgraph

a(CHEBI:"nitric oxide") increases a(CHEBI:peroxynitrite) View Subject | View Object

It is noteworthy that IL-1 beta and IL-18 can activate various cell types, par- ticularly astrocytes and microglia to induce additional cytokine release involving IL-1 beta , IL-6, and IL-18, and also nitric oxide (NO) synthase that can stimulate production of free radical NO, leading to the forma- tion of peroxynitrite that denatures DNA and impairs cellular energy pathways [48, 49]. PubMed:27314526

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Brain
MeSH
Cerebrospinal Fluid
MeSH
Serum
MeSH
Alzheimer Disease
NeuroMMSigDB
Interleukin signaling subgraph
NeuroMMSigDB
Nitric oxide subgraph

a(CHEBI:"nitric oxide") increases act(p(HGNC:CASP3)) View Subject | View Object

NO can also bring about apoptosis of hippocampal neurons via caspase- 3 activity [50] whereas astrocyte-secreted IL-1 beta can increase the production of APP and A beta from neu- rons [51–53] (Fig. 1). PubMed:27314526

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Annotations
Confidence
Medium
MeSH
Hippocampus
MeSH
Alzheimer Disease
NeuroMMSigDB
Amyloidogenic subgraph
NeuroMMSigDB
Caspase subgraph
NeuroMMSigDB
Interleukin signaling subgraph
NeuroMMSigDB
Nitric oxide subgraph

a(CHEBI:"nitric oxide") increases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Additionally, it can induce phosphorylation of the tau protein and promote for- mation of neurofibrillary tangles through the mitogen activated protein kinases-p38 (MAPK-p38) stress pathway [22, 54]. PubMed:27314526

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Annotations
Confidence
High
MeSH
Alzheimer Disease
NeuroMMSigDB
MAPK-JNK subgraph
NeuroMMSigDB
Nitric oxide subgraph
NeuroMMSigDB
Tau protein subgraph

a(CHEBI:"nitric oxide") increases bp(GO:"p38MAPK cascade") View Subject | View Object

Additionally, it can induce phosphorylation of the tau protein and promote for- mation of neurofibrillary tangles through the mitogen activated protein kinases-p38 (MAPK-p38) stress pathway [22, 54]. PubMed:27314526

Appears in Networks:
Annotations
Confidence
High
MeSH
Alzheimer Disease
NeuroMMSigDB
MAPK-JNK subgraph
NeuroMMSigDB
Nitric oxide subgraph
NeuroMMSigDB
Tau protein subgraph

a(CHEBI:"nitric oxide") decreases act(complex(GO:"NF-kappaB complex")) View Subject | View Object

Furthermore, nitric oxide (NO), a well characterized repressor of NF-κB activation and signaling [174, 175], causes a mitigation in neurogenesis PubMed:28745240

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Annotations
MeSH
Hippocampus
MeSH
Alzheimer Disease

a(CHEBI:"nitric oxide") decreases bp(GO:neurogenesis) View Subject | View Object

Furthermore, nitric oxide (NO), a well characterized repressor of NF-κB activation and signaling [174, 175], causes a mitigation in neurogenesis PubMed:28745240

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Annotations
MeSH
Hippocampus
MeSH
Alzheimer Disease

a(CHEBI:"nitric oxide") negativeCorrelation a(CHEBI:heme) View Subject | View Object

The main mediator of these adverse effects is thought to be free haem via its effects on NO scavenging, pro-inflammatory cytokine responses, and reactive oxygen species (ROS) generation. PubMed:25307023

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Plasma
MeSH
Urine
MeSH
Anemia, Hemolytic, Autoimmune
Text Location
Review

a(CHEBI:"nitric oxide") increases bp(GO:"relaxation of smooth muscle") View Subject | View Object

NO is also known as endothelial- derived relaxing factor, because of its role in signalling to relax the smooth muscle lining the vasculature (Rother et al, 2005). PubMed:25307023

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Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Plasma
MeSH
Urine
MeSH
Anemia, Hemolytic, Autoimmune
Text Location
Review

a(CHEBI:"nitric oxide") increases a(CHEBI:"3',5'-cyclic GMP") View Subject | View Object

As such, it nitrosylates the haem-moiety of guanylate cyclase, thereby stimulating formation of cyclic guanine monophosphate (cGMP), which then initiates calcium-dependent vasodilation (Olson et al, 2004). PubMed:25307023

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Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Plasma
MeSH
Urine
MeSH
Anemia, Hemolytic, Autoimmune
Text Location
Review

a(CHEBI:"nitric oxide") decreases path(MESH:"Platelet Aggregation") View Subject | View Object

Furthermore, NO has a fundamental role in normal vascular physiology by inhibiting both platelet aggregation and endothelial adhesion molecule expression, as detailed below PubMed:25307023

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Plasma
MeSH
Urine
MeSH
Anemia, Hemolytic, Autoimmune
Text Location
Review

a(CHEBI:"nitric oxide") decreases a(MESH:"Cell Adhesion Molecules") View Subject | View Object

Furthermore, NO has a fundamental role in normal vascular physiology by inhibiting both platelet aggregation and endothelial adhesion molecule expression, as detailed below PubMed:25307023

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Plasma
MeSH
Urine
MeSH
Anemia, Hemolytic, Autoimmune
Text Location
Review

a(CHEBI:"nitric oxide") decreases act(complex(p(HGNC:F13A1), p(HGNC:F13B))) View Subject | View Object

Finally, NO may also affect coagulation by inhibiting Factor XIII activity (Catani et al, 1998). PubMed:25307023

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Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Plasma
MeSH
Urine
MeSH
Anemia, Hemolytic, Autoimmune
Text Location
Review

a(CHEBI:"nitric oxide") increases path(MESH:"Clot Retraction") View Subject | View Object

Factor XIII stabilizes clots by catalysing fibrin monomer cross-linking; thus, NO deficiency enhances clot stability and reduces clot dissolution. PubMed:25307023

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Plasma
MeSH
Urine
MeSH
Anemia, Hemolytic, Autoimmune
Text Location
Review

a(CHEBI:"nitric oxide") decreases path(MESH:Thrombosis) View Subject | View Object

Therefore, decreased NO bioavailability affects vascular tone, platelet and endothelial function and coagulation, thus increasing thrombotic risk. PubMed:25307023

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Plasma
MeSH
Urine
MeSH
Anemia, Hemolytic, Autoimmune
Text Location
Review

a(CHEBI:"nitric oxide") decreases bp(MESH:"Platelet Activation") View Subject | View Object

Platelets may be activated during haemolysis by several different mechanisms involving decreased NO levels, increased pro-inflammatory cytokines and mediators, and ROS. PubMed:25307023

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Plasma
MeSH
Urine
MeSH
Anemia, Hemolytic, Autoimmune
Text Location
Review

a(CHEBI:"nitric oxide") decreases bp(MESH:"Platelet Activation") View Subject | View Object

Another mechanism for platelet activation by RBC lysate is extracellular hemoglobin, which enhances platelet activation by lowering NO bioavailability [ 29]. PubMed:28458720

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MeSH
Veins
Text Location
Review

a(CHEBI:"nitric oxide") decreases bp(MESH:"Platelet Activation") View Subject | View Object

Both processes decrease the availability of NO, which normally maintains smooth muscle cell relaxation, inhibits platelet activation and aggregation, and has anti-inflammatory effects on the endothelium. PubMed:29929138

Appears in Networks:
Annotations
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

a(CHEBI:"nitric oxide") decreases bp(MESH:"Platelet Aggregation") View Subject | View Object

Platelet deposition and adhesion at sites of subintimal injury are increased by free haemoglobin or inhibition of NO production; this effect can be prevented by infusions of L-arginine, the precursor of NO (Olsen et al, 1996). PubMed:25307023

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Plasma
MeSH
Urine
MeSH
Anemia, Hemolytic, Autoimmune
Text Location
Review

a(CHEBI:"nitric oxide") decreases bp(MESH:"Platelet Aggregation") View Subject | View Object

Both processes decrease the availability of NO, which normally maintains smooth muscle cell relaxation, inhibits platelet activation and aggregation, and has anti-inflammatory effects on the endothelium. PubMed:29929138

Appears in Networks:
Annotations
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

a(CHEBI:"nitric oxide") negativeCorrelation p(HGNC:HBB) View Subject | View Object

Plasma hemoglobin scavenges nitric oxide and causes vasoconstriction, platelet aggregation and inflammation9,22–24. PubMed:27515135

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Text Location
Introduction

a(CHEBI:"nitric oxide") increases bp(GO:vasoconstriction) View Subject | View Object

The extensive crosslinkage of cell-free hemoglobin in a high-molecular weight HBOC retains cell-free hemoglobin dimers in the intravascular compartment, thereby preventing extravasation 112 of cell-free hemoglobin into the muscular layer of the arteries where local NO consumption can trigger vasoconstriction (25). PubMed:28314763

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Text Location
Introduction

a(CHEBI:"nitric oxide") negativeCorrelation bp(GO:vasoconstriction) View Subject | View Object

Heme promotes endothelial dysfunction by inducing the expression of adhesion molecules and reducing nitric oxide (NO) availability, which causes vasoconstriction [9-14]. PubMed:28400318

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

a(CHEBI:"nitric oxide") decreases bp(GO:"endothelial cell activation") View Subject | View Object

Because nitric oxide is known to prevent activation of endothelial cells and platelets, this nitric oxide deficiency promotes cellular activation. PubMed:28458720

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Review

a(CHEBI:"nitric oxide") decreases path(MESH:Inflammation) View Subject | View Object

Both processes decrease the availability of NO, which normally maintains smooth muscle cell relaxation, inhibits platelet activation and aggregation, and has anti-inflammatory effects on the endothelium. PubMed:29929138

Appears in Networks:
Annotations
Cell Ontology (CL)
platelet
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

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.