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p(HBP:"Tau oligomers", var("p.Lys280del"))

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Entity

Name
Tau oligomers
Namespace
HBP
Namespace Version
20190207
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/cf4d8bb88754f036b943b4d94ad96e103dcb7149/export/hbp-names.belns

Appears in Networks 1

Extracellular low-n oligomers of tau cause selective synaptotoxicity without affecting cell viability v1.0.0

In-Edges 3

a(MESH:Microglia) regulates act(p(HBP:"Tau oligomers", var("p.Lys280del"))) View Subject | View Object

We reasoned that microglia and other cell types in the hippocampus might act as mediators for the cytotoxicity caused by TauRDΔK oligomers, which could explain why cytotoxicity was not observed in the cell culture systems. PubMed:28528849

Appears in Networks:

p(HBP:"Tau isoform F (441 aa)", var("p.Lys280del")) increases p(HBP:"Tau oligomers", var("p.Lys280del")) View Subject | View Object

During early stages of assembly, there is some increase in ThS intensity, combined with a pronounced increase in ANSfluorescence (Fig. 2Aand B), which is due to oligomers, indicating a change in conformation without increase in beta-structure PubMed:28528849

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p(HBP:"Tau oligomers") hasVariant p(HBP:"Tau oligomers", var("p.Lys280del")) View Subject | View Object

Appears in Networks:

Out-Edges 29

p(HBP:"Tau oligomers", var("p.Lys280del")) increases p(HBP:"Tau fibrils", var("p.Lys280del")) View Subject | View Object

During the transition from oligomers to polymers, the ANS fluorescence remains roughly constant, whereas ThS fluorescence increases strongly (Fig. 2B) PubMed:28528849

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p(HBP:"Tau oligomers", var("p.Lys280del")) increases bp(GO:"cell death") View Subject | View Object

To address this question, we first applied the oligomers directly after the purification of the protein eluting from the Butyl FF 16/ 10 column (without buffer exchange; 1, 5, and 10 mM) to SHSY5Y cells and observed a variety of toxic effects, including pronounced reduction in the cell viability (by MTT assay, Fig. 3A), increase in apoptotic cells (by Hoechst staining, Supplementary Fig. 4A), loss of mitochondrial membrane potential (by JC1 assay, Supplementary Fig. 4B), caspase 3/7 activation (Supplementary Fig. 4C-D), and cytochrome-c release (Supplementary Fig. 4), within 5 hours of incubation. PubMed:28528849

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
SK-N-SH

p(HBP:"Tau oligomers", var("p.Lys280del")) causesNoChange bp(GO:"cell death") View Subject | View Object

Consistent with this, NeuN staining of the slices fixed after 48 hours of treatment with TauRDΔK oligomers revealed no reduction in the neuronal number in all regions of the hippocampus (CA1, CA3, and DG) (Fig. 3C and D, Supplementary Fig. 7), confirming that TauRDΔK oligomers do not cause cell death in the OHSC model as well. PubMed:28528849

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Annotations
MeSH
CA1 Region, Hippocampal
MeSH
CA2 Region, Hippocampal
MeSH
CA3 Region, Hippocampal

p(HBP:"Tau oligomers", var("p.Lys280del")) increases bp(GO:"apoptotic process") View Subject | View Object

To address this question, we first applied the oligomers directly after the purification of the protein eluting from the Butyl FF 16/ 10 column (without buffer exchange; 1, 5, and 10 mM) to SHSY5Y cells and observed a variety of toxic effects, including pronounced reduction in the cell viability (by MTT assay, Fig. 3A), increase in apoptotic cells (by Hoechst staining, Supplementary Fig. 4A), loss of mitochondrial membrane potential (by JC1 assay, Supplementary Fig. 4B), caspase 3/7 activation (Supplementary Fig. 4C-D), and cytochrome-c release (Supplementary Fig. 4), within 5 hours of incubation. PubMed:28528849

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
SK-N-SH

p(HBP:"Tau oligomers", var("p.Lys280del")) increases bp(GO:"negative regulation of mitochondrial membrane potential") View Subject | View Object

To address this question, we first applied the oligomers directly after the purification of the protein eluting from the Butyl FF 16/ 10 column (without buffer exchange; 1, 5, and 10 mM) to SHSY5Y cells and observed a variety of toxic effects, including pronounced reduction in the cell viability (by MTT assay, Fig. 3A), increase in apoptotic cells (by Hoechst staining, Supplementary Fig. 4A), loss of mitochondrial membrane potential (by JC1 assay, Supplementary Fig. 4B), caspase 3/7 activation (Supplementary Fig. 4C-D), and cytochrome-c release (Supplementary Fig. 4), within 5 hours of incubation. PubMed:28528849

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
SK-N-SH

p(HBP:"Tau oligomers", var("p.Lys280del")) increases act(p(HGNC:CASP3)) View Subject | View Object

To address this question, we first applied the oligomers directly after the purification of the protein eluting from the Butyl FF 16/ 10 column (without buffer exchange; 1, 5, and 10 mM) to SHSY5Y cells and observed a variety of toxic effects, including pronounced reduction in the cell viability (by MTT assay, Fig. 3A), increase in apoptotic cells (by Hoechst staining, Supplementary Fig. 4A), loss of mitochondrial membrane potential (by JC1 assay, Supplementary Fig. 4B), caspase 3/7 activation (Supplementary Fig. 4C-D), and cytochrome-c release (Supplementary Fig. 4), within 5 hours of incubation. PubMed:28528849

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
SK-N-SH

p(HBP:"Tau oligomers", var("p.Lys280del")) increases act(p(HGNC:CASP7)) View Subject | View Object

To address this question, we first applied the oligomers directly after the purification of the protein eluting from the Butyl FF 16/ 10 column (without buffer exchange; 1, 5, and 10 mM) to SHSY5Y cells and observed a variety of toxic effects, including pronounced reduction in the cell viability (by MTT assay, Fig. 3A), increase in apoptotic cells (by Hoechst staining, Supplementary Fig. 4A), loss of mitochondrial membrane potential (by JC1 assay, Supplementary Fig. 4B), caspase 3/7 activation (Supplementary Fig. 4C-D), and cytochrome-c release (Supplementary Fig. 4), within 5 hours of incubation. PubMed:28528849

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
SK-N-SH

p(HBP:"Tau oligomers", var("p.Lys280del")) increases sec(p(HGNC:CYCS)) View Subject | View Object

To address this question, we first applied the oligomers directly after the purification of the protein eluting from the Butyl FF 16/ 10 column (without buffer exchange; 1, 5, and 10 mM) to SHSY5Y cells and observed a variety of toxic effects, including pronounced reduction in the cell viability (by MTT assay, Fig. 3A), increase in apoptotic cells (by Hoechst staining, Supplementary Fig. 4A), loss of mitochondrial membrane potential (by JC1 assay, Supplementary Fig. 4B), caspase 3/7 activation (Supplementary Fig. 4C-D), and cytochrome-c release (Supplementary Fig. 4), within 5 hours of incubation. PubMed:28528849

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
SK-N-SH

p(HBP:"Tau oligomers", var("p.Lys280del")) causesNoChange a(GO:membrane) View Subject | View Object

There was no significant change in the LDH release in oligomer-treated cells compared with controls indicating that TauRDΔK oligomers do not compromise the membrane integrity (Supplementary Fig. 5G-H). PubMed:28528849

Appears in Networks:
Annotations
Experimental Factor Ontology (EFO)
SK-N-SH

p(HBP:"Tau oligomers", var("p.Lys280del")) decreases a(MESH:"Dendritic Spines") View Subject | View Object

In this case, there was a dramatic loss (up to 50%) of spines in TauRDΔK oligomer-treated cells compared with monomer-treated cells (Fig. 4A and B, bar 3). PubMed:28528849

Appears in Networks:

p(HBP:"Tau oligomers", var("p.Lys280del")) decreases a(MESH:"Dendritic Spines") View Subject | View Object

Drebrin, a neuronal actin-binding protein involved in spinogenesis and synaptogenesis, was decreased by up to 60% consistent with the reduced number of spines (Fig. 4D, bars 3, 6, and 9). PubMed:28528849

Appears in Networks:

p(HBP:"Tau oligomers", var("p.Lys280del")) decreases a(MESH:"Dendritic Spines") View Subject | View Object

Endogenous tau protein retained its normal axonal localization and did not missort into the cell body and dendrites (Fig. 6A8), although there was a reduction in the spine density (Fig. 6B6) in the TauRDΔK oligomer-treated neurons. PubMed:28528849

Appears in Networks:
Annotations
MeSH
Neurons

p(HBP:"Tau oligomers", var("p.Lys280del")) decreases a(MESH:"Dendritic Spines") View Subject | View Object

The results revealed that both TauRDΔK and TauFLΔK oligomers reduce the density of spines up to 50% compared with the buffer-treated cells. PubMed:28528849

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p(HBP:"Tau oligomers", var("p.Lys280del")) decreases a(GO:postsynapse) View Subject | View Object

PSD-95, a marker of postsynaptic spines, decreased up to 50% in the TauRDΔK oligomer-treated cells, compared with buffer- and monomer-treated cells PubMed:28528849

Appears in Networks:
Annotations
MeSH
Dendritic Spines

p(HBP:"Tau oligomers", var("p.Lys280del")) decreases p(HGNC:GRIA1) View Subject | View Object

Similarly, the GluR1 subunits of a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (characteristic of mature spines and necessary for LTP and calcium signaling) decreased in the oligomer-treated samples up to 60%. PubMed:28528849

Appears in Networks:

p(HBP:"Tau oligomers", var("p.Lys280del")) decreases p(HGNC:DBN1) View Subject | View Object

Drebrin, a neuronal actin-binding protein involved in spinogenesis and synaptogenesis, was decreased by up to 60% consistent with the reduced number of spines (Fig. 4D, bars 3, 6, and 9). PubMed:28528849

Appears in Networks:

p(HBP:"Tau oligomers", var("p.Lys280del")) decreases p(HGNC:SYP) View Subject | View Object

We also looked at the presynaptic protein synaptophysin, which was not significantly altered in TauRDΔK oligomer-treated cells compared with buffer- or monomer-treated cells (Fig 4D, bar 12). However, at higher concentration, synaptophysin tends to be reduced. PubMed:28528849

Appears in Networks:

p(HBP:"Tau oligomers", var("p.Lys280del")) increases a(CHEBI:"reactive oxygen species") View Subject | View Object

We observed an oligomer-dependent increase in the ROS production in the mature rat primary hippocampal neurons in all cellular compartments (Fig. 5A). PubMed:28528849

Appears in Networks:
Annotations
MeSH
Hippocampus
MeSH
Neurons

p(HBP:"Tau oligomers", var("p.Lys280del")) increases p(HGNC:NOX1) View Subject | View Object

We indeed found that there is an overexpression (w15%) of Nox1 protein (a component of NADPH oxidase complex) by Western blot, suggesting the role of NADPH oxidase complex as a potential source of ROS PubMed:28528849

Appears in Networks:

p(HBP:"Tau oligomers", var("p.Lys280del")) increases act(complex(GO:"NADPH oxidase complex")) View Subject | View Object

We indeed found that there is an overexpression (w15%) of Nox1 protein (a component of NADPH oxidase complex) by Western blot, suggesting the role of NADPH oxidase complex as a potential source of ROS PubMed:28528849

Appears in Networks:

p(HBP:"Tau oligomers", var("p.Lys280del")) increases act(complex(GO:"NADPH oxidase complex")) View Subject | View Object

These findings suggest that the ROS production induced by extracellular TauRDΔK oligomers might cause the activation of NADPH oxidase complex PubMed:28528849

Appears in Networks:

p(HBP:"Tau oligomers", var("p.Lys280del")) causesNoChange p(HGNC:CYBB) View Subject | View Object

However, we did not find significant changes in the expression level of Nox2 protein (another component of NADPH oxidase complex) (Fig. 5C). PubMed:28528849

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p(HBP:"Tau oligomers", var("p.Lys280del")) increases bp(GO:"cellular calcium ion homeostasis") View Subject | View Object

The ratio of 340 to 380 nm in TauRDΔK oligomer-treated cells showed a steady concentration-dependent increase in the intracellular calcium with a maximum reached at 20 minutes of incubation with oligomers (10 mM) occurring in all cell compartments (Fig. 5D; arrows). PubMed:28528849

Appears in Networks:
Annotations
MeSH
Hippocampus
MeSH
Neurons

p(HBP:"Tau oligomers", var("p.Lys280del")) causesNoChange p(HGNC:MAPT, pmod(Ph, Ser, 262)) View Subject | View Object

We did not observe any increase in the phosphorylation of the tau repeat domain (as seen by the antibody 12E8) after treating the neurons with TauRDΔK oligomers. PubMed:28528849

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p(HBP:"Tau oligomers", var("p.Lys280del")) causesNoChange p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

We also checked the phosphorylation of tau at other sites (e.g., using the antibody AT8, reacting only with the endogenous tau) and did not observe an increase in the phosphorylation. PubMed:28528849

Appears in Networks:

p(HBP:"Tau oligomers", var("p.Lys280del")) causesNoChange p(HGNC:MAPT, pmod(Ph, Thr, 205)) View Subject | View Object

We also checked the phosphorylation of tau at other sites (e.g., using the antibody AT8, reacting only with the endogenous tau) and did not observe an increase in the phosphorylation. PubMed:28528849

Appears in Networks:

p(HBP:"Tau oligomers", var("p.Lys280del")) causesNoChange tloc(p(HGNC:MAPT), fromLoc(GO:axon), toLoc(GO:"cell body")) View Subject | View Object

Endogenous tau protein retained its normal axonal localization and did not missort into the cell body and dendrites (Fig. 6A8), although there was a reduction in the spine density (Fig. 6B6) in the TauRDΔK oligomer-treated neurons. PubMed:28528849

Appears in Networks:
Annotations
MeSH
Neurons

p(HBP:"Tau oligomers", var("p.Lys280del")) causesNoChange tloc(p(HGNC:MAPT), fromLoc(GO:axon), toLoc(MESH:"Dendritic Spines")) View Subject | View Object

Endogenous tau protein retained its normal axonal localization and did not missort into the cell body and dendrites (Fig. 6A8), although there was a reduction in the spine density (Fig. 6B6) in the TauRDΔK oligomer-treated neurons. PubMed:28528849

Appears in Networks:
Annotations
MeSH
Neurons

p(HBP:"Tau oligomers", var("p.Lys280del")) decreases a(GO:synapse) View Subject | View Object

Tau oligomers from TauRDΔK and TauFLΔK mice reduced the density of the synapses by w50%, whereas tau from wild-type mice had no effect on the density (Fig. 7G). PubMed:28528849

Appears in Networks:

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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.