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Appears in Networks 6

In-Edges 19

deg(a(CHEBI:acetylcholine)) increases a(CHEBI:choline) View Subject | View Object

Choline that is released by ACh hydrolysis in the synaptic cleft is continuously reuptaken into the presynaptic cholinergic neuron by an active transport system (see Fig. 1) PubMed:26813123

a(MESH:"Cholinergic Neurons") increases a(CHEBI:choline) View Subject | View Object

Although cholinergic neurons can synthesize choline, the de novo synthesis contributes only with a very small fraction of the total choline that is needed for ACh synthesis (see Fig. 1) PubMed:26813123

p(HGNC:SLC5A7) increases a(CHEBI:choline) View Subject | View Object

CHT1 is mainly found in cholinergic neurons [92-94] and is responsible for supplying choline for the synthesis of ACh PubMed:26813123

bp(GO:"action potential initiation") increases tloc(a(CHEBI:choline), fromLoc(GO:"extracellular region"), toLoc(GO:intracellular)) View Subject | View Object

Interestingly, it has been demonstrated that an increase in neuronal firing can lead to an increase in choline uptake and in the synthesis of ACh PubMed:26813123

bp(GO:"action potential initiation") increases tloc(a(CHEBI:choline), fromLoc(GO:"synaptic cleft"), toLoc(MESH:"Cholinergic Neurons")) View Subject | View Object

It is possible that the presence of CHT1 in the membrane of synaptic vesicles and the consequent increase in CHT1 relocation to the plasma membrane following neuronal depolarization could explain why an increase in neuronal firing promotes increased choline reuptake and, thus, ACh synthesis PubMed:26813123

p(HGNC:SLC5A7) increases tloc(a(CHEBI:choline), fromLoc(GO:"synaptic cleft"), toLoc(MESH:"Cholinergic Neurons")) View Subject | View Object

Choline that is released by ACh hydrolysis in the synaptic cleft is continuously reuptaken into the presynaptic cholinergic neuron by an active transport system (see Fig. 1) PubMed:26813123

p(HGNC:SLC5A7) increases tloc(a(CHEBI:choline), fromLoc(GO:"synaptic cleft"), toLoc(MESH:"Cholinergic Neurons")) View Subject | View Object

Two choline transporters have been identified in neurons: a ubiquitous, low-affinity, sodium-independent transporter that can only be inhibited by high concentrations of hemicholinium-3 (HC-3) (Ki of about 50 μM), and a highaffinity, sodium-dependent, HC-3-sensitive (Ki of 10-100 nM) choline transporter (CHT1) PubMed:26813123

p(HGNC:SLC5A7) increases tloc(a(CHEBI:choline), fromLoc(GO:"synaptic cleft"), toLoc(MESH:"Cholinergic Neurons")) View Subject | View Object

It is possible that the presence of CHT1 in the membrane of synaptic vesicles and the consequent increase in CHT1 relocation to the plasma membrane following neuronal depolarization could explain why an increase in neuronal firing promotes increased choline reuptake and, thus, ACh synthesis PubMed:26813123

p(MGI:App, var("?")) decreases tloc(a(CHEBI:choline), fromLoc(GO:"extracellular region"), toLoc(GO:intracellular)) View Subject | View Object

In addition, quantitative autoradiography assay revealed that choline uptake was reduced in the hippocampus of these animals and that the expression of muscarinic and nicotinic cholinergic receptors was diminished PubMed:26813123

a(CHEBI:nifedipine) decreases act(a(CHEBI:choline)) View Subject | View Object

As shown in Fig. 5, A–C, nifedipine was found to decrease the peak calcium response to choline in PC12 cells (peak: 795.00% ΔF/Fθ ± 107.1%) by 56.94% (p = 0.003), whereas prolonging the duration of the choline-induced calcium transient (AUC: 749.50% ΔF/Fθ2 × s ± 64.02%) in the same cell. PubMed:26088141

act(a(MESH:"Calcium Channels")) association act(a(CHEBI:choline)) View Subject | View Object

In α7345–348A nAChR expressing cells, nifedipine had no effect on the peak or the duration of the calcium transient (peak: 957.00% ΔF/Fθ ± 252.2%; AUC: 333.33% ΔF/Fθ2 × s ± 91.53%) relative to choline treatment alone (Fig. 5, A–C). The findings suggest that choline-induced calcium responses in PC12 cells involve the activity of VGCC (37, 38). PubMed:26088141

bp(MESH:"Pleckstrin Homology Domains") association a(CHEBI:choline) View Subject | View Object

Treatment of PC12 cells with 10 mM choline was associated with a translocation of PH-mCherry from the cell surface as determined by the presence of the fluorescence signal within 1 μm of the edge of the cell into the cytosol of the GC (Fig. 6, A and B). Pre-treatment of cells with SP abolished this translocation (Fig. 6B). PubMed:26088141

a(CHEBI:phosphatidylcholine) increases a(CHEBI:choline) View Subject | View Object

Variants in the gene for phosphatidylethanolamine methyl transferase, which synthesizes phosphatidylcholine and thus provides a source of choline, are also associated with choline deficiency and with schizophrenia PubMed:21482353

path(MESH:Depression) increases a(CHEBI:choline) View Subject | View Object

using in vivo proton NMR imaging, levels of choline (the rate-limiting precursor to endogeneous ACh) were shown to be increased in the brains of patients with depression217 and in the prefrontal cortex of adolescents with depression218 compared with the control group. PubMed:19721446

Out-Edges 13

a(CHEBI:choline) increases act(p(FPLX:CHRN)) View Subject | View Object

Another important aspect of this diffusive ACh signal is that its eventual hydrolysis creates choline, which also activates and desensitizes nAChRs in a subtype-selective manner (54, 55). PubMed:17009926

a(CHEBI:choline) increases a(CHEBI:acetylcholine) View Subject | View Object

CHT1 is mainly found in cholinergic neurons [92-94] and is responsible for supplying choline for the synthesis of ACh PubMed:26813123

act(a(CHEBI:choline)) increases a(CHEBI:"calcium(2+)") View Subject | View Object

PC12 cells transfected with α7345–348A showed a reduction in choline-mediated calcium responses. PubMed:26088141

act(a(CHEBI:choline)) association act(a(MESH:"Calcium Channels")) View Subject | View Object

In α7345–348A nAChR expressing cells, nifedipine had no effect on the peak or the duration of the calcium transient (peak: 957.00% ΔF/Fθ ± 252.2%; AUC: 333.33% ΔF/Fθ2 × s ± 91.53%) relative to choline treatment alone (Fig. 5, A–C). The findings suggest that choline-induced calcium responses in PC12 cells involve the activity of VGCC (37, 38). PubMed:26088141

a(CHEBI:choline) association bp(MESH:"Pleckstrin Homology Domains") View Subject | View Object

Treatment of PC12 cells with 10 mM choline was associated with a translocation of PH-mCherry from the cell surface as determined by the presence of the fluorescence signal within 1 μm of the edge of the cell into the cytosol of the GC (Fig. 6, A and B). Pre-treatment of cells with SP abolished this translocation (Fig. 6B). PubMed:26088141

a(CHEBI:choline) increases bp(MESH:"Pleckstrin Homology Domains") View Subject | View Object

Sequential imaging of PH-mCherry and GCaMP5G confirms that choline promotes a rise in intracellular calcium and PH-mCherry translocation in the same cellular compartment (Fig. 6, B and C). Cytoplasmic translocation of PH-mCherry occurred on a slower time scale (40 s after choline application) than peak calcium responses (∼1 s after choline application). These kinetics are consistent with the translocation of the PH domain sensor in the cell (20, 29). PubMed:26088141

a(CHEBI:choline) decreases complex(p(FPLX:"G_protein"), p(HGNC:CHRNA7)) View Subject | View Object

As shown in Fig. 8, A and B, IP of the α7 using the C-20 antibody suggests that choline application attenuates G protein binding with the nAChR. Choline treatment resulted in a 56% reduction in Gαq and 47% reduction in Gβ association within the α7 nAChR complex (Fig. 8B). PubMed:26088141

a(CHEBI:choline) decreases complex(p(HGNC:CHRNA7), p(HGNC:GNAQ)) View Subject | View Object

As shown in Fig. 8, A and B, IP of the α7 using the C-20 antibody suggests that choline application attenuates G protein binding with the nAChR. Choline treatment resulted in a 56% reduction in Gαq and 47% reduction in Gβ association within the α7 nAChR complex (Fig. 8B). PubMed:26088141

a(CHEBI:choline) decreases complex(p(HGNC:CHRNA7), p(HGNCGENEFAMILY:"G protein subunits beta")) View Subject | View Object

As shown in Fig. 8, A and B, IP of the α7 using the C-20 antibody suggests that choline application attenuates G protein binding with the nAChR. Choline treatment resulted in a 56% reduction in Gαq and 47% reduction in Gβ association within the α7 nAChR complex (Fig. 8B). PubMed:26088141

a(CHEBI:choline) increases act(a(MESH:"alpha7 Nicotinic Acetylcholine Receptor")) View Subject | View Object

As we will see below, the mystery of somatodendritic nAChRs can also be resolved by the sensitivity of alpha7 nAChRs to constant levels of another agonist, choline PubMed:21482353

a(CHEBI:choline) increases act(a(HBP:"alpha-7-containing nAChR")) View Subject | View Object

A possible candidate is choline, which, in addition to its other development roles, activates alpha7 nAChRs at levels several fold higher than acetylcholine PubMed:21482353

a(CHEBI:choline) increases bp(MESH:Neuroprotection) View Subject | View Object

Choline, like nicotine, can protect neural cells from cytotoxicity that is induced by growth factor deprivation152 or exposure to the glutamate analogue AMPA (alpha-amino-3-hydroxy-5-methyl-4- isoxazole propionic acid)153. PubMed:19721446

a(CHEBI:choline) decreases act(a(MESH:"alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid")) View Subject | View Object

Choline, like nicotine, can protect neural cells from cytotoxicity that is induced by growth factor deprivation152 or exposure to the glutamate analogue AMPA (alpha-amino-3-hydroxy-5-methyl-4- isoxazole propionic acid)153. PubMed:19721446

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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.