Inhibition of choline uptake in syncytial microvillus membrane vesicles of human term placenta

Aa, E.M. van der; Wouterse, Alfons C.; Peereboom-Stegeman, J.H.J. Copius; Rüssel, Frans G. M.

doi:10.1016/0006-2952(95)02081-0

Cited by 9 publications

(4 citation statements)

References 14 publications

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“…Maternal plasma concentrations of betaine, dimethylglycine, and TMAO at delivery were strongly associated with cord plasma concentrations of these metabolites. In contrast, maternal plasma free choline at delivery was only weakly associated with cord plasma free choline concentrations, possibly because of the active transport of choline from maternal plasma to placental tissue and/or the rapid uptake and metabolism of choline in the fetal compartment (30)(31)(32). The strong associations between plasma betaine and TMAO concentrations in maternal and fetal compartments indicate that these metabolites are transferred from the mother to the fetus (28).…”

Section: Discussionmentioning

confidence: 94%

Maternal Choline Status, but Not Fetal Genotype, Influences Cord Plasma Choline Metabolite Concentrations

Visentin

Masih

Plumptre

et al. 2015

The Journal of Nutrition

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Section: Discussionmentioning

confidence: 94%

Maternal Choline Status, but Not Fetal Genotype, Influences Cord Plasma Choline Metabolite Concentrations

Visentin

Masih

Plumptre

et al. 2015

The Journal of Nutrition

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“…Organic cations such as hemicholinium-3 (HC-3) have been shown to inhibit up to 75% of choline uptake into human term placenta. [27][28][29] In addition to using choline deficient media, we incubated the cells for 3 h with 5 μmol/L HC-3 to prevent choline uptake into the cells. In a subset of the experiments, we verified the choline concentrations in the cell pellets to ensure that the cells incubated in choline deficient media or with HC-3 contained lower choline compared to the control cells that were incubated at 50 μmol/L choline.…”

Section: Methodsmentioning

confidence: 99%

“…Organic cations such as hemicholinium‐3 (HC‐3) have been shown to inhibit up to 75% of choline uptake into human term placenta 27–29 . In addition to using choline deficient media, we incubated the cells for 3 h with 5 μmol/L HC‐3 to prevent choline uptake into the cells.…”

Section: Methodsmentioning

confidence: 99%

An exploratory study on the effect of choline and folate deficiency on levels of vascularization proteins and transcription factors in first trimester trophoblast HTR‐8/SVneo cells

Engelhart

Pfitzner

Obeid

2023

J of Obstet and Gynaecol

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Aims We studied the effect of choline and folate deficiencies on levels of predetermined placental proteins during early development. Methods We incubated HTR‐8/SVneo cells under choline and folate deficiency conditions and measured levels of some placental proteins using ELISA methods. Results Concentrations of LRP2 protein in cell lysates were higher in cells incubated in choline and folate deficient media compared to the control media (mean [SD] = 2.95 [1.30] vs. 1.65 [0.27] ng/mg protein, p = 0.004). The levels of LRP2 protein in lysates of cells incubated in choline and folate deficient media were significantly higher than the concentrations in lysates of cells incubated in choline deficient but folate sufficient media (1.96 [0.28] ng/mg protein) or those incubated in choline sufficient but folate deficient media (1.77 [0.24] ng/mg protein) (p < 0.05 for both). The cellular levels of CDX2 protein were significantly higher in cells incubated in choline and folate deficient media compared to the control media (1.78 [0.60] vs. 0.99 [0.42] pg/mg protein, p = 0.002); and compared to CDX2 levels in cells incubated in choline deficient but folate sufficient media (0.87 [0.13] pg/mg protein, p < 0.001) or in choline sufficient but folate deficient media (0.96 [0.16] pg/mg protein, p < 0.001). The levels of sFLT‐1 and IGF1 in culture media and that of EOMES in HTR‐8/SVneo cell lysates remained unchanged under all deficiency conditions. Discussion LRP2 and CDX2 are likely to be molecular targets for early choline and folate deficiencies in human trophoblast cells. The results should be confirmed in animal models and in other models of placental cells.

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“…Its specificity, which was tested by few substrates only, seems to be similar to that of the luminal choline+ transporter in the proximal tubule. The question about electrogenicity, Na+ dependence and Km values of choline+ transport in intestine, placenta and aortic endothelial cells was extensively discussed by Bevan and Kinne [3], Takano et al [18] and Van der Aa et al [26]. So far no new aspects can be added to this issue.…”

Section: Specificitymentioning

confidence: 97%

Luminal transport system for choline+ in relation to the other organic cation transport systems in the rat proximal tubule

Ullrich

Rumrich

1996

Pflugers Arch - Eur J Physiol

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The efflux of [3H] choline+ from the proximal tubular lumen was measured by using the stop-flow microperfusion method. The 2-s efflux of [3H] choline+ follows kinetics with a Michaelis constant, Km = 0.18 mmol x l-1, maximal flux, Jmax = 0.43 pmol x cm-1 x s-1 and a permeability term = 38.0 micron2 small middle dots-1. Replacement of Na+ by N-methyl-D-glucamine+ or Li+, or a change of luminal pH do not alter choline+ efflux. Replacement of Na+ by Cs+ inhibits 2-s choline+ (0. 01 mmol x l-1) efflux by 22% and replacement by K+ inhibits by 49%, indicating that the electrical potential difference across the brush border membrane acts as driving force for choline+ transport. Comparing the apparent luminal inhibitory constant values for choline (app. Ki,l,choline+) with the chemical structure of inhibiting substrates, it was found that the inhibitory potency of amines with high pKa values, i.e. high basicity, and of quaternary ammonium compounds (tetraethyl to tetrahexylammonium) increases with their hydrophobicity in a similar manner as was observed previously against the contraluminal N1-methylnicotinamide (NMeN+) transporter and the luminal H+/organic cation (N-methyl-4-phenylpyridinium) (MPP+) exchanger. Independently of their hydrophobicity, an increase in the inhibitory potency of the homologous series of aminoquinolines against the choline+ transporter was observed with increasing pKa values, i.e. increasing basicity, as was found previously against the two other organic cation transporters. A third parameter influencing the interaction with the choline+ transporter is the presence of two amino groups with high pKa values or one amino group and a permanent positive charge, as is documented with the two-ring aminostyryl and rhodamine compounds, as well as three-ring aminoacridine, aminophenanthrene and cyanine compounds. Thus with the aminostyryl, pyridinium+, rhodamine, phenanthridium+ and cyanine+ dyes app.Ki,l,choline+ values of between 0.01 and 0.07 mmol x l-1 have been found. A fourth parameter influencing the choline+ transporter is the presence of an OH group on the C atom next to that bearing the N atom (as in choline+) or an ester-OCOR group (acetylcholine+, butyrylcholine+) or a thioester-SCOR-group (acetylthiocholine+, butyrylthiocholine+); or an -OP(OH)2(OR) group (glycerylphosphoryl-choline+), resulting in app.Ki,l,choline+ values of 0.3-1.0 mmol x l-1. Thus the substrates for the luminal choline+ transporter have general features in common with the luminal H+/organic cation exchanger and the contraluminal organic cation transporter, i.e. hydrophobicity and basicity. Additional parameters for interaction are an OH (or similar) group positioned a favourable distance from the N atom or a second amino/ammonium group in multi-ring compounds.

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Inhibition of choline uptake in syncytial microvillus membrane vesicles of human term placenta

Cited by 9 publications

References 14 publications

Maternal Choline Status, but Not Fetal Genotype, Influences Cord Plasma Choline Metabolite Concentrations

Maternal Choline Status, but Not Fetal Genotype, Influences Cord Plasma Choline Metabolite Concentrations

An exploratory study on the effect of choline and folate deficiency on levels of vascularization proteins and transcription factors in first trimester trophoblast HTR‐8/SVneo cells

Luminal transport system for choline+ in relation to the other organic cation transport systems in the rat proximal tubule

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