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a(CHEBI:Thrombin)

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Entity

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

Appears in Networks 2

Tau clearance mechanisms and their possible role in the pathogenesis of Alzheimer disease v1.0.0

Heme Curation v0.0.1-dev

Mechanistic knowledge surrounding heme

In-Edges 9

a(MESH:"Endothelial Cells") increases sec(a(CHEBI:Thrombin)) View Subject | View Object

Thrombin is a serine protease that is a well characterized component of the coagulation cascade. It is typically produced and secreted by endothelial cells, including those in the brain in response to hemodynamic injury. PubMed:24027553

Appears in Networks:
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MeSH
Brain
Text Location
Review

p(HGNC:MAPT, pmod(Ph)) decreases act(a(CHEBI:Thrombin)) View Subject | View Object

Interestingly, phosphorylation of tau also appears to disrupt some thrombin cleavage sites, changing the pattern of cleavage without impeding the thrombin-mediated proteolysis (14, 28). PubMed:24027553

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path(MESH:"Alzheimer Disease") increases a(CHEBI:Thrombin, loc(MESH:Microvessels)) View Subject | View Object

A recent study showed that thrombin is elevated in microvessels isolated from AD brain compared to microvessels from control brain (33). Additionally, thrombin was present in the CSF of AD patients but not in that of controls (33). This is important, as thrombin can act as a neurotoxin by activating intracellular signaling cascades causing neurite retraction and stimulating apoptosis (34–36) PubMed:24027553

Appears in Networks:
Annotations
MeSH
Brain
Text Location
Review

path(MESH:"Alzheimer Disease") increases a(CHEBI:Thrombin, loc(MESH:"Cerebrospinal Fluid")) View Subject | View Object

A recent study showed that thrombin is elevated in microvessels isolated from AD brain compared to microvessels from control brain (33). Additionally, thrombin was present in the CSF of AD patients but not in that of controls (33). This is important, as thrombin can act as a neurotoxin by activating intracellular signaling cascades causing neurite retraction and stimulating apoptosis (34–36) PubMed:24027553

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Text Location
Review

path(MESH:"Neurofibrillary Tangles") association a(CHEBI:Thrombin) View Subject | View Object

There are also data to suggest that thrombin may act intracellularly to mediate tau pathology. Thrombin is expressed within neurons and astrocytes in both normal and AD brain (38). In AD brain the staining pattern for thrombin and prothrombin was characteristic of the pattern of NFTs, although these structures were not colabeled with antibodies for tau (38). PubMed:24027553

Appears in Networks:
Annotations
MeSH
Alzheimer Disease
Text Location
Review

a(CHEBI:"phosphatidyl-L-serine") positiveCorrelation a(CHEBI:Thrombin) View Subject | View Object

These RBC microparticles can initiate and propogate thrombin generation (Rubin et al, 2013). PubMed:25307023

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

a(HM:schistocytosis) positiveCorrelation a(CHEBI:Thrombin) View Subject | View Object

However, 6 years later, Heyes and co-workers demonstrated in an experimental study in rats that infusions of thrombin induce DIC accompanied with hemolysis and schistocytosis [89]. PubMed:29956069

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

path(MESH:"Disseminated Intravascular Coagulation") positiveCorrelation a(CHEBI:Thrombin) View Subject | View Object

However, 6 years later, Heyes and co-workers demonstrated in an experimental study in rats that infusions of thrombin induce DIC accompanied with hemolysis and schistocytosis [89]. PubMed:29956069

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

path(MESH:Hemolysis) positiveCorrelation a(CHEBI:Thrombin) View Subject | View Object

However, 6 years later, Heyes and co-workers demonstrated in an experimental study in rats that infusions of thrombin induce DIC accompanied with hemolysis and schistocytosis [89]. PubMed:29956069

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

Out-Edges 16

a(CHEBI:Thrombin) increases bp(GO:coagulation) View Subject | View Object

Thrombin is a serine protease that is a well characterized component of the coagulation cascade. It is typically produced and secreted by endothelial cells, including those in the brain in response to hemodynamic injury. PubMed:24027553

Appears in Networks:
Annotations
MeSH
Brain
Text Location
Review

act(a(CHEBI:Thrombin)) increases deg(p(HGNC:MAPT)) View Subject | View Object

Evidence supporting a role for thrombin in tau proteolysis came initially from an in vitro study showing that thrombin degraded recombinant full-length tau from the N-terminus yielding a 25-kDa fragment, while preserving the microtubule binding repeat domain (13). PubMed:24027553

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Review

act(a(CHEBI:Thrombin)) increases deg(p(HGNC:MAPT)) View Subject | View Object

Also of importance is understanding the role of non-degradative cleavage in influencing the eventual clearance of tau. Numerous proteases have been shown to proteolyze tau including aminopeptidases (10–12), thrombin (13–15), human high temperature requirement serine protease A1 (HTRA1) (16), calpain (17–20), and caspases (21–24). PubMed:24027553

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Text Location
Review

a(CHEBI:Thrombin) increases bp(HBP:"neurite retraction") View Subject | View Object

A recent study showed that thrombin is elevated in microvessels isolated from AD brain compared to microvessels from control brain (33). Additionally, thrombin was present in the CSF of AD patients but not in that of controls (33). This is important, as thrombin can act as a neurotoxin by activating intracellular signaling cascades causing neurite retraction and stimulating apoptosis (34–36) PubMed:24027553

Appears in Networks:
Annotations
Text Location
Review

a(CHEBI:Thrombin) increases bp(GO:"apoptotic process") View Subject | View Object

A recent study showed that thrombin is elevated in microvessels isolated from AD brain compared to microvessels from control brain (33). Additionally, thrombin was present in the CSF of AD patients but not in that of controls (33). This is important, as thrombin can act as a neurotoxin by activating intracellular signaling cascades causing neurite retraction and stimulating apoptosis (34–36) PubMed:24027553

Appears in Networks:
Annotations
Text Location
Review

a(CHEBI:Thrombin) increases bp(GO:"apoptotic process") View Subject | View Object

Thrombin may also be influencing tau pathology, as treatment of immortalized hippocampal neuronal cells (HT22 cells) with thrombin resulted in the formation of thioflavin-S positive tau aggregates within 24 h, followed by an increase in cell death at 72 h (37). PubMed:24027553

Appears in Networks:
Annotations
MeSH
Hippocampus
Text Location
Review

a(CHEBI:Thrombin) increases a(HBP:"Tau aggregates") View Subject | View Object

Thrombin may also be influencing tau pathology, as treatment of immortalized hippocampal neuronal cells (HT22 cells) with thrombin resulted in the formation of thioflavin-S positive tau aggregates within 24 h, followed by an increase in cell death at 72 h (37). PubMed:24027553

Appears in Networks:
Annotations
MeSH
Hippocampus
Text Location
Review

a(CHEBI:Thrombin) association path(MESH:"Neurofibrillary Tangles") View Subject | View Object

There are also data to suggest that thrombin may act intracellularly to mediate tau pathology. Thrombin is expressed within neurons and astrocytes in both normal and AD brain (38). In AD brain the staining pattern for thrombin and prothrombin was characteristic of the pattern of NFTs, although these structures were not colabeled with antibodies for tau (38). PubMed:24027553

Appears in Networks:
Annotations
MeSH
Alzheimer Disease
Text Location
Review

act(a(CHEBI:Thrombin)) increases p(HGNC:MAPT, frag("1_?")) View Subject | View Object

Evidence supporting a role for thrombin in tau proteolysis came initially from an in vitro study showing that thrombin degraded recombinant full-length tau from the N-terminus yielding a 25-kDa fragment, while preserving the microtubule binding repeat domain (13). PubMed:24027553

Appears in Networks:
Annotations
Text Location
Review

act(a(CHEBI:Thrombin)) causesNoChange p(HGNC:MAPT, frag("561_685")) View Subject | View Object

Evidence supporting a role for thrombin in tau proteolysis came initially from an in vitro study showing that thrombin degraded recombinant full-length tau from the N-terminus yielding a 25-kDa fragment, while preserving the microtubule binding repeat domain (13). PubMed:24027553

Appears in Networks:
Annotations
Text Location
Review

act(a(CHEBI:Thrombin)) increases deg(p(HGNC:MAPT, frag("561_685"))) View Subject | View Object

A later study, however, showed that in N2a neuroblastoma cells expressing a construct of only the tau repeat domain, thrombin cleavage could still occur, indicating additional cleavage sites (15). Similar results were observed in an in vitro assay (15). PubMed:24027553

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Text Location
Review

act(a(CHEBI:Thrombin)) increases act(p(HGNCGENEFAMILY:Caspases)) View Subject | View Object

Thrombin signaling can also activate caspases (36). Proteasomal impairment appears to be upstream of caspase activation, as inhibiting the proteasome with epoxomicin (EPX) led to activation of caspase-3 in primary neurons (63) and in a neuroblastoma cell line expressing wild-type tau (64). PubMed:24027553

Appears in Networks:
Annotations
Text Location
Review

a(CHEBI:Thrombin) positiveCorrelation a(CHEBI:"phosphatidyl-L-serine") View Subject | View Object

These RBC microparticles can initiate and propogate thrombin generation (Rubin et al, 2013). PubMed:25307023

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

a(CHEBI:Thrombin) positiveCorrelation path(MESH:"Disseminated Intravascular Coagulation") View Subject | View Object

However, 6 years later, Heyes and co-workers demonstrated in an experimental study in rats that infusions of thrombin induce DIC accompanied with hemolysis and schistocytosis [89]. PubMed:29956069

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

a(CHEBI:Thrombin) positiveCorrelation path(MESH:Hemolysis) View Subject | View Object

However, 6 years later, Heyes and co-workers demonstrated in an experimental study in rats that infusions of thrombin induce DIC accompanied with hemolysis and schistocytosis [89]. PubMed:29956069

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

a(CHEBI:Thrombin) positiveCorrelation a(HM:schistocytosis) View Subject | View Object

However, 6 years later, Heyes and co-workers demonstrated in an experimental study in rats that infusions of thrombin induce DIC accompanied with hemolysis and schistocytosis [89]. PubMed:29956069

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

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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.